2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:Ta30,Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage ≥3 and/or treated) and postnatal age. A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; β = 0.68; 95% CI, 0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; β = 0.21; 95% CI, 0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. ClinicalTrials.gov Identifier: NCT03201588.31:T10b9, Importance Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. Objective To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. Design, Setting, and Participants This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. Exposures All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. Main Outcomes and Measures Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage ≥3 and/or treated) and postnatal age. Results A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; β = 0.68; 95% CI, 0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; β = 0.21; 95% CI, 0.13-0.29; Q &lt;.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. Conclusions and Relevance In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. Trial Registration ClinicalTrials.gov Identifier: NCT03201588 32:T76a,Focal segmental glomerulosclerosis (FSGS) is a podocytopathy that is diagnosed based on characteristic histopathological lesions. Certain forms of FSGS with underlying genetic variants associated with the disease, including variants in podocyte proteins, as well as apolipoprotein L1 (APOL1) risk alleles, and variants in collagen type IV (COL4) α3, α4, and α5 (COL4A3-5) proteins, are typically resistant to current treatments. The DUPLEX clinical trial assessed the efficacy and safety of sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA), in patients with biopsy-proven or genetic FSGS and demonstrated a greater antiproteinuric effect over 108 weeks compared to the active control irbesartan. This post hoc, exploratory analysis assessed the efficacy of sparsentan in the subset of patients enrolled in DUPLEX who had pathogenic variants in genes coding for podocyte proteins, COL4A3-5 variants, and APOL1 high-risk genotypes, altogether referred to as genetic FSGS (gFSGS). Next-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints. These findings support sparsentan's antiproteinuric benefit in patients with gFSGS, a subgroup that is often resistant to other therapeutic interventions.33:Tc8d, Background: Focal segmental glomerulosclerosis (FSGS) is a podocytopathy that is diagnosed based on characteristic histopathological lesions. Certain forms of FSGS with underlying genetic variants associated with the disease, including variants in podocyte proteins, as well as apolipoprotein L1 ( APOL1 ) risk alleles, and variants in collagen type IV (COL4) α3, α4, and α5 ( COL4A3-5 ) proteins, are typically resistant to current treatments. Methods: The DUPLEX clinical trial assessed the efficacy and safety of sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA), in patients with biopsy-proven or genetic FSGS and demonstrated a greater antiproteinuric effect over 108 weeks compared to the active control irbesartan. This post hoc, exploratory analysis assessed the efficacy of sparsentan in the subset of patients enrolled in DUPLEX who had pathogenic variants in genes coding for podocyte proteins, COL4A3-5 variants, and APOL1 high-risk genotypes, altogether referred to as genetic FSGS (gFSGS). Results: Next-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints. Conclusions: These findings support sparsentan’s antiproteinuric benefit in patients with gFSGS, a subgroup that is often resistant to other therapeutic interventions. 34:T7e2,In real-world chronic obstructive pulmonary disease (COPD) care, poor adherence often leads to treatment discontinuations. Discontinuing inhaled corticosteroids (ICS) can trigger withdrawal effects transiently increasing exacerbation risk; but evidence for long-acting muscarinic antagonists (LAMA) withdrawal remains limited. We performed a post hoc analysis of the 52-week, double-blind, Effect of Indacaterol Glycopyrronium versus Fluticasone Salmeterol on COPD Exacerbations trial that compared long-acting beta-2 agonist (LABA)+LAMA with LABA+ICS in 3362 patients with moderate-to-severe COPD and exacerbation history. Potential withdrawal effects after discontinuing LAMA or ICS were suggested by monthly exacerbation incidence plots during the first quarter of follow-up. Participants were stratified by their baseline use of these therapies, and outcomes were compared between the first and subsequent quarters among those who continued versus discontinued each treatment. Multivariable mixed-effects models assessed differences in exacerbation rates, with temporal variation in treatment effects interpreted as indicative of withdrawal effects. Discontinuing LAMA was associated with a marked, transient increase in moderate-to-severe exacerbations during the first versus subsequent quarters (p=0.001; rate ratio up to 2.2 (95% CI 1.2 to 4.1) in the subgroup least influenced by concomitant ICS use). This observation was not confirmed for severe exacerbations, likely due to low event count. In contrast, discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), though the difference for moderate-to-severe events did not reach statistical significance. Importantly, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count. Our findings suggest potent LAMA and ICS treatment withdrawal effects on exacerbations, highlighting the importance of treatment adherence and accounting for withdrawal effects in clinical trials. NCT01782326.35:Tb94, Background In real-world chronic obstructive pulmonary disease (COPD) care, poor adherence often leads to treatment discontinuations. Discontinuing inhaled corticosteroids (ICS) can trigger withdrawal effects transiently increasing exacerbation risk; but evidence for long-acting muscarinic antagonists (LAMA) withdrawal remains limited. Methods We performed a post hoc analysis of the 52-week, double-blind, Effect of Indacaterol Glycopyrronium versus Fluticasone Salmeterol on COPD Exacerbations trial that compared long-acting beta-2 agonist (LABA)+LAMA with LABA+ICS in 3362 patients with moderate-to-severe COPD and exacerbation history. Potential withdrawal effects after discontinuing LAMA or ICS were suggested by monthly exacerbation incidence plots during the first quarter of follow-up. Participants were stratified by their baseline use of these therapies, and outcomes were compared between the first and subsequent quarters among those who continued versus discontinued each treatment. Multivariable mixed-effects models assessed differences in exacerbation rates, with temporal variation in treatment effects interpreted as indicative of withdrawal effects. Results Discontinuing LAMA was associated with a marked, transient increase in moderate-to-severe exacerbations during the first versus subsequent quarters (p=0.001; rate ratio up to 2.2 (95% CI 1.2 to 4.1) in the subgroup least influenced by concomitant ICS use). This observation was not confirmed for severe exacerbations, likely due to low event count. In contrast, discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), though the difference for moderate-to-severe events did not reach statistical significance. Importantly, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count. Conclusion Our findings suggest potent LAMA and ICS treatment withdrawal effects on exacerbations, highlighting the importance of treatment adherence and accounting for withdrawal effects in clinical trials. Trial registration number NCT01782326 . 36:Tc53,Itch is the most burdensome symptom in atopic dermatitis (AD) and prurigo nodularis (PN) and is associated with significant psychological distress, sleep deprivation and impaired quality of life. Achieving rapid control of itch is expected to minimize symptomatology and disease burden. Nemolizumab, which targets the interleukin 31 (IL-31) pathway, rapidly relieved itch in Phase 2 trials; thus, a post hoc analysis of four pivotal randomized controlled clinical trials of nemolizumab in AD and PN was performed to further evaluate the improvement of itch over the first 14 days of therapy. Data from ARCADIA 1 and 2 in AD (N = 1728) and OLYMPIA 1 and 2 in PN (N = 560) were analysed. Patients reported itch intensity and sleep disturbance daily. Differences in the proportion of itch and sleep responders (patients with ≥4-point improvement from baseline in peak pruritus numerical rating scale [PP-NRS] or sleep disturbance [SD-NRS] score) between nemolizumab and placebo groups were calculated. Nemolizumab rapidly reduced itch in AD (ARCADIA 1 and 2), with a difference versus placebo in PP-NRS responders apparent by Day 2 (pooled data: 10.7% vs. 2.9%; 95% CI: 5.6-10.1; p < 0.0001) that steadily increased through Day 14. Nemolizumab also reduced itch rapidly in PN (OLYMPIA 1 and 2); a difference versus placebo occurred by Day 2 (pooled data: 17.2% vs. 3.7%; 95% CI: 6.8-16.7; p < 0.0001). Early improvement (Day 2) was also observed in sleep in nemolizumab-treated patients. In pooled analyses in AD, 9.9% (nemolizumab) versus 4.6% (placebo; 95% CI: 2.8-7.7; p = 0.0001) were SD-NRS responders and in PN, 13.4% versus 4.3% (95% CI: 4.0-13.0; p = 0.0013). Itch and sleep response data in individual studies were consistent with the pooled data. This analysis confirms previously reported data that nemolizumab relieves itch and sleep disturbance by Day 2 in patients with moderate-to-severe AD and PN, indicating that targeting the IL-31 pathway presents an important way to achieve rapid itch response. People with skin diseases such as atopic dermatitis and prurigo nodularis experience itch, which can be severe and can interfere with their daily lives with missed school or work days and psychological well‐being impairment, especially when the itching lasts for a long time as is often the case with these diseases. Itching can also make it hard to sleep. A medicine that quickly stops itching can help people with atopic dermatitis and prurigo nodularis to feel better. Nemolizumab is a medicine that is approved to treat atopic dermatitis and prurigo nodularis and it works fast to stop itching. This study looked at data from four clinical studies of nemolizumab, focusing on how itch changed during the first 14 days of treatment. Patients in the studies who had atopic dermatitis or prurigo nodularis recorded daily in diaries how much itch they felt and how they slept. The researchers found that nemolizumab started working to control itching in just 2 days and patients also slept better. Less itching and better sleep may improve well‐being in people with atopic dermatitis and prurigo nodularis.37:Tcac,Abstract Background/Objectives Itch is the most burdensome symptom in atopic dermatitis (AD) and prurigo nodularis (PN) and is associated with significant psychological distress, sleep deprivation and impaired quality of life. Achieving rapid control of itch is expected to minimize symptomatology and disease burden. Nemolizumab, which targets the interleukin 31 (IL‐31) pathway, rapidly relieved itch in Phase 2 trials; thus, a post hoc analysis of four pivotal randomized controlled clinical trials of nemolizumab in AD and PN was performed to further evaluate the improvement of itch over the first 14 days of therapy. Methods Data from ARCADIA 1 and 2 in AD ( N = 1728) and OLYMPIA 1 and 2 in PN ( N = 560) were analysed. Patients reported itch intensity and sleep disturbance daily. Differences in the proportion of itch and sleep responders (patients with ≥4‐point improvement from baseline in peak pruritus numerical rating scale [PP‐NRS] or sleep disturbance [SD‐NRS] score) between nemolizumab and placebo groups were calculated. Results Nemolizumab rapidly reduced itch in AD (ARCADIA 1 and 2), with a difference versus placebo in PP‐NRS responders apparent by Day 2 (pooled data: 10.7% vs. 2.9%; 95% CI: 5.6–10.1; p < 0.0001) that steadily increased through Day 14. Nemolizumab also reduced itch rapidly in PN (OLYMPIA 1 and 2); a difference versus placebo occurred by Day 2 (pooled data: 17.2% vs. 3.7%; 95% CI: 6.8–16.7; p < 0.0001). Early improvement (Day 2) was also observed in sleep in nemolizumab‐treated patients. In pooled analyses in AD, 9.9% (nemolizumab) versus 4.6% (placebo; 95% CI: 2.8–7.7; p = 0.0001) were SD‐NRS responders and in PN, 13.4% versus 4.3% (95% CI: 4.0–13.0; p = 0.0013). Itch and sleep response data in individual studies were consistent with the pooled data. Conclusions This analysis confirms previously reported data that nemolizumab relieves itch and sleep disturbance by Day 2 in patients with moderate‐to‐severe AD and PN, indicating that targeting the IL‐31 pathway presents an important way to achieve rapid itch response. 38:T687,Of 308 included participants, 219 (71.1%) were female, 89 (28.9%) were male, and the mean (SD) age was 47.1 (12.2) years. There were 54 participants in the less than 25% weight regain group, 77 in the 25% to less than 50% group, 103 in the 50% to less than 75% group, and 74 in the 75% or more group. Baseline demographic and clinical characteristics were similar across categories. During the initial 36 weeks of tirzepatide treatment, participants' weight decreased and cardiometabolic parameters improved. After withdrawal of tirzepatide, from week 36 to week 88, the mean change in waist circumference increased by weight regain category (<25% weight regain, 0.8 cm; 95% CI, -1.0 to 2.6; 25% to <50%, 5.4 cm; 95% CI, 4.0-6.8; 50% to <75%, 10.1 cm; 95% CI, 8.9-11.3; ≥75%, 14.7 cm; 95% CI, 12.7-16.7; P < .001), as did systolic blood pressure (6.8 mm Hg [95% CI, 3.9-9.7], 7.3 mm Hg [95% CI, 4.8-9.8], 9.6 mm Hg [95% CI, 7.1-12.1], and 10.4 mm Hg [95% CI, 8.0-12.8], respectively; P = .002), non-high-density lipoprotein cholesterol (-0.4% [95% CI, -7.3 to 6.5], 1.6% [95% CI, -2.3 to 5.5], 8.4% [95% CI, 3.9-12.9], and 10.8% [95% CI, 5.3-16.3], respectively), hemoglobin A1c (0.14% [95% CI, 0.06-0.22], 0.15% [95% CI, 0.09-0.21], 0.27% [95% CI, 0.21-0.33], and 0.35% [95% CI, 0.29-0.41], respectively; P < .001), and fasting insulin (-4.0% [95% CI, -20.7 to 12.7], 15.4% [95% CI, 2.3-28.5], 46.2% [95% CI, 29.5-62.9], and 26.3% [95% CI, 9.6-43.0], respectively). Changes at week 88 in waist circumference, non-high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36.39:Tcf0,In the SURMOUNT-4 trial, most adults with obesity who had tirzepatide withdrawn following a 36-week treatment regained weight. The association between the degree of weight regain and cardiometabolic parameters after tirzepatide withdrawal is unknown. To assess changes in cardiometabolic parameters by degree of weight regain after withdrawal of tirzepatide. This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo. Data were collected from March 2021 to May 2023, and data were analyzed from February 2024 to March 2025. After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88). Changes from week 36 to week 88 in cardiometabolic parameters on tirzepatide withdrawal were assessed by the degree of weight regain at week 88 as a percentage of weight lost while receiving tirzepatide from week 0 to 36: less than 25%, 25% to less than 50%, 50% to less than 75%, and 75% or more. Of 308 included participants, 219 (71.1%) were female, 89 (28.9%) were male, and the mean (SD) age was 47.1 (12.2) years. There were 54 participants in the less than 25% weight regain group, 77 in the 25% to less than 50% group, 103 in the 50% to less than 75% group, and 74 in the 75% or more group. Baseline demographic and clinical characteristics were similar across categories. During the initial 36 weeks of tirzepatide treatment, participants' weight decreased and cardiometabolic parameters improved. After withdrawal of tirzepatide, from week 36 to week 88, the mean change in waist circumference increased by weight regain category (<25% weight regain, 0.8 cm; 95% CI, -1.0 to 2.6; 25% to <50%, 5.4 cm; 95% CI, 4.0-6.8; 50% to <75%, 10.1 cm; 95% CI, 8.9-11.3; ≥75%, 14.7 cm; 95% CI, 12.7-16.7; P < .001), as did systolic blood pressure (6.8 mm Hg [95% CI, 3.9-9.7], 7.3 mm Hg [95% CI, 4.8-9.8], 9.6 mm Hg [95% CI, 7.1-12.1], and 10.4 mm Hg [95% CI, 8.0-12.8], respectively; P = .002), non-high-density lipoprotein cholesterol (-0.4% [95% CI, -7.3 to 6.5], 1.6% [95% CI, -2.3 to 5.5], 8.4% [95% CI, 3.9-12.9], and 10.8% [95% CI, 5.3-16.3], respectively), hemoglobin A1c (0.14% [95% CI, 0.06-0.22], 0.15% [95% CI, 0.09-0.21], 0.27% [95% CI, 0.21-0.33], and 0.35% [95% CI, 0.29-0.41], respectively; P < .001), and fasting insulin (-4.0% [95% CI, -20.7 to 12.7], 15.4% [95% CI, 2.3-28.5], 46.2% [95% CI, 29.5-62.9], and 26.3% [95% CI, 9.6-43.0], respectively). Changes at week 88 in waist circumference, non-high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36. In this post hoc analysis of the SURMOUNT-4 trial, among participants with obesity who achieved weight reduction with 36-week tirzepatide treatment, withdrawing tirzepatide led to 25% or greater weight regain in most participants within 1 year and was associated with a greater reversal of their initial cardiometabolic parameter improvements compared with those who maintained weight reduction. These findings underscore the importance of continued obesity treatment. ClinicalTrials.gov Identifier: NCT04660643.3a:T1440, Importance In the SURMOUNT-4 trial, most adults with obesity who had tirzepatide withdrawn following a 36-week treatment regained weight. The association between the degree of weight regain and cardiometabolic parameters after tirzepatide withdrawal is unknown. Objective To assess changes in cardiometabolic parameters by degree of weight regain after withdrawal of tirzepatide. Design, Setting, and Participants This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo. Data were collected from March 2021 to May 2023, and data were analyzed from February 2024 to March 2025. Interventions After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88). Main Outcomes and Measures Changes from week 36 to week 88 in cardiometabolic parameters on tirzepatide withdrawal were assessed by the degree of weight regain at week 88 as a percentage of weight lost while receiving tirzepatide from week 0 to 36: less than 25%, 25% to less than 50%, 50% to less than 75%, and 75% or more. Results Of 308 included participants, 219 (71.1%) were female, 89 (28.9%) were male, and the mean (SD) age was 47.1 (12.2) years. There were 54 participants in the less than 25% weight regain group, 77 in the 25% to less than 50% group, 103 in the 50% to less than 75% group, and 74 in the 75% or more group. Baseline demographic and clinical characteristics were similar across categories. During the initial 36 weeks of tirzepatide treatment, participants’ weight decreased and cardiometabolic parameters improved. After withdrawal of tirzepatide, from week 36 to week 88, the mean change in waist circumference increased by weight regain category (&lt;25% weight regain, 0.8 cm; 95% CI, −1.0 to 2.6; 25% to &lt;50%, 5.4 cm; 95% CI, 4.0-6.8; 50% to &lt;75%, 10.1 cm; 95% CI, 8.9-11.3; ≥75%, 14.7 cm; 95% CI, 12.7-16.7; P &lt; .001), as did systolic blood pressure (6.8 mm Hg [95% CI, 3.9-9.7], 7.3 mm Hg [95% CI, 4.8-9.8], 9.6 mm Hg [95% CI, 7.1-12.1], and 10.4 mm Hg [95% CI, 8.0-12.8], respectively; P = .002), non–high-density lipoprotein cholesterol (−0.4% [95% CI, −7.3 to 6.5], 1.6% [95% CI, −2.3 to 5.5], 8.4% [95% CI, 3.9-12.9], and 10.8% [95% CI, 5.3-16.3], respectively), hemoglobin A 1c (0.14% [95% CI, 0.06-0.22], 0.15% [95% CI, 0.09-0.21], 0.27% [95% CI, 0.21-0.33], and 0.35% [95% CI, 0.29-0.41], respectively; P &lt; .001), and fasting insulin (−4.0% [95% CI, −20.7 to 12.7], 15.4% [95% CI, 2.3-28.5], 46.2% [95% CI, 29.5-62.9], and 26.3% [95% CI, 9.6-43.0], respectively). Changes at week 88 in waist circumference, non–high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36. Conclusions and Relevance In this post hoc analysis of the SURMOUNT-4 trial, among participants with obesity who achieved weight reduction with 36-week tirzepatide treatment, withdrawing tirzepatide led to 25% or greater weight regain in most participants within 1 year and was associated with a greater reversal of their initial cardiometabolic parameter improvements compared with those who maintained weight reduction. These findings underscore the importance of continued obesity treatment. Trial Registration ClinicalTrials.gov Identifier: NCT04660643 3b:T803,OnabotulinumtoxinA (onabotA) is indicated for upper facial lines (UFL). Fear of unnatural-looking outcomes is a frequently reported treatment barrier. Examine patient-reported outcomes (PROs) after onabotA treatment for UFL. A post hoc analysis was conducted on two 12-month pivotal studies of onabotA for forehead and glabellar lines (20 U each), with/without treatment of crow's feet lines (±24 U). This analysis used PROs from the Facial Line Satisfaction Questionnaire: Items 4 (natural look), 5 (treatment effect), 11 (met expectations), and Impact Domain (appearance and psychological impact). The analysis included 458 neurotoxin-naive adults achieving a ≥2-grade improvement in forehead line (FHL) severity on the Facial Wrinkle Scale at Day 30 (primary endpoint). [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'forehead line (FHL)' in this version.] Data were further stratified into millennials and men. At Day 30, 90.5% of all participants, 94.6% of millennials, and 85.7% of men were satisfied with receiving a natural look. Millennials had higher odds of being satisfied with natural outcomes at Day 30. This measure remained > 80% for all groups throughout the 12 months. Additionally, ≥80% were satisfied with the treatment effect, and >90% reported results met expectations. At Day 30, ≥50% reported positive impacts on self-perceived appearance and psychological well-being, but millennials had higher, and men had lower odds of reporting these improvements. Participants achieving a ≥2-grade improvement in FHL severity after onabotA reported high satisfaction with natural outcomes and the treatment effect, with improved self-perceived appearance and psychological well-being. [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'FHL' in this version.] These results may help aesthetic providers and patients address fears regarding unnatural results with onabotA.3c:T9ac,AbstractBackgroundOnabotulinumtoxinA (onabotA) is indicated for upper facial lines (UFL). Fear of unnatural‐looking outcomes is a frequently reported treatment barrier.AimsExamine patient‐reported outcomes (PROs) after onabotA treatment for UFL.MethodsA post hoc analysis was conducted on two 12‐month pivotal studies of onabotA for forehead and glabellar lines (20 U each), with/without treatment of crow's feet lines (±24 U). This analysis used PROs from the Facial Line Satisfaction Questionnaire: Items 4 (natural look), 5 (treatment effect), 11 (met expectations), and Impact Domain (appearance and psychological impact). The analysis included 458 neurotoxin‐naive adults achieving a ≥2‐grade improvement in forehead line (FHL) severity on the Facial Wrinkle Scale at Day 30 (primary endpoint). [Corrections made on 28 December 2023, after first online publication: ‘UFL’ in the previous sentence has been corrected to ‘forehead line (FHL)’ in this version.] Data were further stratified into millennials and men.ResultsAt Day 30, 90.5% of all participants, 94.6% of millennials, and 85.7% of men were satisfied with receiving a natural look. Millennials had higher odds of being satisfied with natural outcomes at Day 30. This measure remained > 80% for all groups throughout the 12 months. Additionally, ≥80% were satisfied with the treatment effect, and >90% reported results met expectations. At Day 30, ≥50% reported positive impacts on self‐perceived appearance and psychological well‐being, but millennials had higher, and men had lower odds of reporting these improvements.ConclusionsParticipants achieving a ≥2‐grade improvement in FHL severity after onabotA reported high satisfaction with natural outcomes and the treatment effect, with improved self‐perceived appearance and psychological well‐being. [Corrections made on 28 December 2023, after first online publication: ‘UFL’ in the previous sentence has been corrected to ‘FHL’ in this version.] These results may help aesthetic providers and patients address fears regarding unnatural results with onabotA.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Post Hoc Analysis: study design Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Post Hoc Analysis (study design). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/study_design/Post%20Hoc%20Analysis\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Study Designs\",\"item\":\"https://www.reachrx.ai/hub/tag/study_design\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Post Hoc Analysis\",\"item\":\"https://www.reachrx.ai/hub/tag/study_design/Post%20Hoc%20Analysis\"}]}}"}}]],["$","$L2f",null,{"title":"Post Hoc Analysis: Research & Clinical Takeaways","description":"Browse Post Hoc Analysis research papers with clear, practical takeaways for your clinical practice.","papers":[{"doi":"10.1007/s13300-026-01875-3","pmid":"42105046","title":"Semaglutide and Cardiovascular Outcomes in People with Type 2 Diabetes: A SUSTAIN-6 Post Hoc Analysis by Weight Loss Category","journal_title":"Diabetes Therapy","journal_issn":"1869-6953","published_at":"2026-05-09T00:00:00.000Z","url":"https://doi.org/10.1007/s13300-026-01875-3","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:28.956Z","updated_at":"2026-05-18T13:25:28.956Z","tags":[{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"sample_size","value":"n=1479","value_numeric":1479},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"warning","value":"Level of evidence assigned as 3 (post hoc observational analysis of an RCT); causality cannot be established.","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"warning","value":"The brand tag 'Ozempic' reflects the injectable semaglutide used in SUSTAIN-6; the paper does not specify formulation branding explicitly.","value_numeric":null},{"paper_doi":"10.1007/s13300-026-01875-3","tag_type":"warning","value":"This is a single-arm post hoc analysis of only the semaglutide group from SUSTAIN-6; absence of a placebo arm means it cannot confirm overall CV benefit of semaglutide, only that benefit does not vary by weight loss category.","value_numeric":null}],"summaries":{"what_studied":"This post hoc analysis of the SUSTAIN-6 trial examined whether the degree of weight loss (none/gain, <5%, 5–10%, >10%) after 56 weeks of semaglutide treatment predicted subsequent MACE risk (weeks 56–104) in 1,479 adults with T2D at high CV risk.","key_result":"MACE incidence did not differ across weight loss categories (P = 0.73); event rates were 1.05% (no loss/gain), 1.69% (<5% loss), 1.06% (5–10% loss), and 0.89% (>10% loss), with no weight loss category showing lower adjusted odds of MACE versus no weight loss/gain.","limitations":"- Post hoc, single-arm, observational design limits causal inference and introduces potential confounding.\n- Weight change was assessed only at 56 weeks; interim fluctuations were not captured.\n- No placebo comparator arm was included, so the absolute CV benefit of semaglutide vs. placebo cannot be quantified within this analysis.","practice_takeaway":"Clinicians should not expect the CV benefit of semaglutide to scale with the amount of weight lost — patients who lose little or no weight on semaglutide may still derive cardioprotection. Weight loss alone should not be used as a surrogate for CV risk reduction when managing T2D with GLP-1 receptor agonists."}},{"doi":"10.1016/j.ard.2026.03.030","pmid":"42067428","title":"Impact of tofacitinib on growth in patients with juvenile idiopathic arthritis","journal_title":"Annals of the Rheumatic Diseases","journal_issn":"0003-4967","published_at":"2026-04-30T00:00:00.000Z","url":"https://doi.org/10.1016/j.ard.2026.03.030","source_score":24,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-13T06:21:54.675Z","updated_at":"2026-09-13T06:21:54.675Z","tags":[{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"brand","value":"Xeljanz","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"condition","value":"Juvenile Idiopathic Arthritis","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"generic","value":"tofacitinib","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"sample_size","value":"n=225","value_numeric":225},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"warning","value":"Biomarker analysis was conducted in a subset of 137 patients over only 18 weeks, which may not reflect long-term endocrine effects.","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"warning","value":"No comparator arm (e.g., methotrexate or biologic DMARD) was included, making it difficult to isolate tofacitinib's specific contribution to growth outcomes.","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"warning","value":"Post hoc design: causality cannot be established; results should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.03.030","tag_type":"warning","value":"The brand name 'Xeljanz' was inferred from tofacitinib; confirm proprietary name applies to the pediatric formulation used in this trial.","value_numeric":null}],"summaries":{"what_studied":"This post hoc analysis evaluated the effect of long-term tofacitinib (a JAK inhibitor) on growth velocity, height Z-scores, and biomarkers of growth hormone (GH) function and bone metabolism in 225 patients with JIA (primarily polyarticular-course), with a median follow-up of 3.6 years.","key_result":"Children ≤12 years showed greater-than-expected height velocities; those >12 years grew as expected for age. Height Z-scores were largely stable overall, but pubertal patients with a baseline height Z-score < −1.0 showed a significant increase in height Z-score at 24 months (P < .05). IGF-1 levels rose from baseline to 18 weeks in patients aged 6–12 years; IGF-1, IGFBP-3, and osteocalcin were unchanged in the overall population.","limitations":"Post hoc design limits causal inference. No control arm means growth outcomes cannot be definitively attributed to tofacitinib vs. disease improvement or natural history. Biomarker data were available for only a subset (n=137) over a short 18-week window.","practice_takeaway":"Tofacitinib does not appear to suppress growth in children with JIA and may support catch-up growth in shorter pubertal patients. Clinicians can be reassured that long-term tofacitinib use is not associated with concerning changes in GH signaling or bone metabolism markers."}},{"doi":"10.1016/j.waojou.2025.101159","pmid":null,"title":"Clinical remission in patients with severe eosinophilic asthma treated with benralizumab over 24 months: Post hoc analysis of the ANANKE study","journal_title":"World Allergy Organization Journal","journal_issn":"1939-4551","published_at":"2026-01-14T00:00:00.000Z","url":"https://doi.org/10.1016/j.waojou.2025.101159","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-16","doi":"10.1016/j.waojou.2025.101159","days":"7","issn":"1939-4551","rank":"3","field":"Clinical Medicine","score":"3","category":"Allergy","categories":["Allergy"],"_categories":["Allergy"]},"pubmed":null,"crossref":{"DOI":"10.1016/j.waojou.2025.101159","URL":"https://doi.org/10.1016/j.waojou.2025.101159","ISSN":["1939-4551"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S193945512500136X?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S193945512500136X?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":"101159","type":"journal-article","issue":"2","score":1,"title":["Clinical remission in patients with severe eosinophilic asthma treated with benralizumab over 24 months: Post hoc analysis of the ANANKE study"],"author":[{"given":"Giorgio Walter","family":"Canonica","sequence":"first","affiliation":[]},{"given":"Gianenrico","family":"Senna","sequence":"additional","affiliation":[]},{"given":"Luisa","family":"Brussino","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Aliani","sequence":"additional","affiliation":[]},{"given":"Elena","family":"Altieri","sequence":"additional","affiliation":[]},{"given":"Pietro","family":"Bracciale","sequence":"additional","affiliation":[]},{"given":"Maria Filomena","family":"Caiaffa","sequence":"additional","affiliation":[]},{"given":"Paolo","family":"Cameli","sequence":"additional","affiliation":[]},{"given":"Marco","family":"Caminati","sequence":"additional","affiliation":[]},{"given":"Cristiano","family":"Caruso","sequence":"additional","affiliation":[]},{"given":"Stefano","family":"Centanni","sequence":"additional","affiliation":[]},{"given":"Fausto","family":"De Michele","sequence":"additional","affiliation":[]},{"given":"Stefano","family":"Del Giacco","sequence":"additional","affiliation":[]},{"given":"Fabiano","family":"Di Marco","sequence":"additional","affiliation":[]},{"given":"Laura","family":"Malerba","sequence":"additional","affiliation":[]},{"given":"Francesco","family":"Menzella","sequence":"additional","affiliation":[]},{"given":"Paola","family":"Rogliani","sequence":"additional","affiliation":[]},{"given":"Micaela","family":"Romagnoli","sequence":"additional","affiliation":[]},{"given":"Pietro","family":"Schino","sequence":"additional","affiliation":[]},{"given":"Jan Walter","family":"Schroeder","sequence":"additional","affiliation":[]},{"given":"Alessandra","family":"Vultaggio","sequence":"additional","affiliation":[]},{"given":"Maria","family":"D'Amato","sequence":"additional","affiliation":[]},{"given":"Girolamo","family":"Pelaia","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,2]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":"19","created":{"date-time":"2026-01-14T04:33:21Z","timestamp":1768365201000,"date-parts":[[2026,1,14]]},"indexed":{"date-time":"2026-01-16T01:19:23Z","timestamp":1768526363459,"date-parts":[[2026,1,16]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000,"date-parts":[[2026,2,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000,"date-parts":[[2026,2,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"http://creativecommons.org/licenses/by-nc-nd/4.0/","start":{"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000,"date-parts":[[2025,12,8]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S193945512500136X"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"Clinical remission in patients with severe eosinophilic asthma treated with benralizumab over 24 months: Post hoc analysis of the ANANKE study"},{"name":"journaltitle","label":"Journal Title","value":"World Allergy Organization Journal"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.waojou.2025.101159"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2025 The Author(s). Published by Elsevier Inc. on behalf of World Allergy Organization."}],"deposited":{"date-time":"2026-01-14T04:33:24Z","timestamp":1768365204000,"date-parts":[[2026,1,14]]},"issn-type":[{"type":"print","value":"1939-4551"}],"published":{"date-parts":[[2026,2]]},"publisher":"Elsevier BV","reference":[{"DOI":"10.1016/S2213-2600(23)00415-0","key":"10.1016/j.waojou.2025.101159_bib1","year":"2024","issue":"2","author":"Lommatzsch","volume":"12","first-page":"96","unstructured":null,"article-title":"Pioneering a paradigm shift in asthma management: remission as a treatment goal","journal-title":"Lancet Respir Med","doi-asserted-by":"crossref"},{"DOI":null,"key":"10.1016/j.waojou.2025.101159_bib2","year":"2024","issue":null,"author":"Canonica","volume":null,"first-page":"1","unstructured":null,"article-title":"SANI clinical remission definition: a useful tool in severe asthma management","journal-title":"J Asthma","doi-asserted-by":null},{"DOI":"10.1016/S0140-6736(22)00331-2","key":"10.1016/j.waojou.2025.101159_bib3","year":"2022","issue":"10335","author":"Lommatzsch","volume":"399","first-page":"1664","unstructured":null,"article-title":"Disease-modifying anti-asthmatic drugs","journal-title":"Lancet","doi-asserted-by":"crossref"},{"DOI":"10.1186/s12931-023-02475-6","key":"10.1016/j.waojou.2025.101159_bib4","year":"2023","issue":"1","author":"Wang","volume":"24","first-page":"169","unstructured":null,"article-title":"Global, regional, and national burden of asthma and its attributable risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019","journal-title":"Respir Res","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.rmed.2018.06.025","key":"10.1016/j.waojou.2025.101159_bib5","year":"2018","issue":null,"author":"Coumou","volume":"141","first-page":"81","unstructured":null,"article-title":"Diagnosing persistent blood eosinophilia in asthma with single blood eosinophil or exhaled nitric oxide level","journal-title":"Respir Med","doi-asserted-by":"crossref"},{"DOI":"10.1080/14712598.2020.1809651","key":"10.1016/j.waojou.2025.101159_bib6","year":"2020","issue":"12","author":"Bakakos","volume":"20","first-page":"1427","unstructured":null,"article-title":"Biologics in severe asthma: the overlap endotype - opportunities and challenges","journal-title":"Expert Opin Biol Ther","doi-asserted-by":"crossref"},{"DOI":"10.1183/23120541.00100-2015","key":"10.1016/j.waojou.2025.101159_bib7","year":"2016","issue":"2","author":"de Groot","volume":"2","first-page":null,"unstructured":null,"article-title":"Clinical profile of patients with adult-onset eosinophilic asthma","journal-title":"ERJ Open Res","doi-asserted-by":"crossref"},{"DOI":"10.1183/09031936.00201813","key":"10.1016/j.waojou.2025.101159_bib8","year":"2014","issue":"1","author":"Schleich","volume":"44","first-page":"97","unstructured":null,"article-title":"Importance of concomitant local and systemic eosinophilia in uncontrolled asthma","journal-title":"Eur Respir J","doi-asserted-by":"crossref"},{"DOI":"10.1136/thoraxjnl-2017-210531","key":"10.1016/j.waojou.2025.101159_bib9","year":"2018","issue":"2","author":"Kerkhof","volume":"73","first-page":"116","unstructured":null,"article-title":"Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population","journal-title":"Thorax","doi-asserted-by":"crossref"},{"DOI":null,"key":"10.1016/j.waojou.2025.101159_bib10","year":"2024","issue":null,"author":"Bonini","volume":null,"first-page":"1","unstructured":null,"article-title":"Asthma remission one, none and one-hundred thousand: the relevance of the patient's view","journal-title":"J Asthma","doi-asserted-by":null},{"DOI":"10.1016/j.jaci.2019.12.006","key":"10.1016/j.waojou.2025.101159_bib11","year":"2020","issue":"3","author":"Menzies-Gow","volume":"145","first-page":"757","unstructured":null,"article-title":"An expert consensus framework for asthma remission as a treatment goal","journal-title":"J Allergy Clin Immunol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jaip.2023.07.041","key":"10.1016/j.waojou.2025.101159_bib12","year":"2023","issue":"12","author":"Canonica","volume":"11","first-page":"3629","unstructured":null,"article-title":"Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus","journal-title":"J Allergy Clin Immunol Pract","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.arbres.2024.04.002","key":"10.1016/j.waojou.2025.101159_bib13","year":"2024","issue":"8","author":"Álvarez-Gutiérrez","volume":"60","first-page":"503","unstructured":null,"article-title":"Spanish Consensus on Remission in Asthma (REMAS)","journal-title":"Arch Bronconeumol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jaci.2010.04.004","key":"10.1016/j.waojou.2025.101159_bib14","year":"2010","issue":"6","author":"Kolbeck","volume":"125","first-page":"1344","unstructured":null,"article-title":"MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function","journal-title":"J Allergy Clin Immunol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.rmed.2016.01.003","key":"10.1016/j.waojou.2025.101159_bib15","year":"2016","issue":null,"author":"Pham","volume":"111","first-page":"21","unstructured":null,"article-title":"Reductions in eosinophil biomarkers by benralizumab in patients with asthma","journal-title":"Respir Med","doi-asserted-by":"crossref"},{"DOI":"10.1016/S0140-6736(16)31324-1","key":"10.1016/j.waojou.2025.101159_bib16","year":"2016","issue":"10056","author":"Bleecker","volume":"388","first-page":"2115","unstructured":null,"article-title":"Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial","journal-title":"Lancet","doi-asserted-by":"crossref"},{"DOI":"10.1016/S0140-6736(16)31322-8","key":"10.1016/j.waojou.2025.101159_bib17","year":"2016","issue":"10056","author":"FitzGerald","volume":"388","first-page":"2128","unstructured":null,"article-title":"Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial","journal-title":"Lancet","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa1703501","key":"10.1016/j.waojou.2025.101159_bib18","year":"2017","issue":"25","author":"Nair","volume":"376","first-page":"2448","unstructured":null,"article-title":"Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma","journal-title":"N Engl J Med","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jaip.2021.07.058","key":"10.1016/j.waojou.2025.101159_bib19","year":"2021","issue":"12","author":"Korn","volume":"9","first-page":"4381","unstructured":null,"article-title":"Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to 5 Years","journal-title":"J Allergy Clin Immunol Pract","doi-asserted-by":"crossref"},{"DOI":"10.1186/s12931-023-02439-w","key":"10.1016/j.waojou.2025.101159_bib20","year":"2023","issue":"1","author":"Vultaggio","volume":"24","first-page":"135","unstructured":null,"article-title":"Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study","journal-title":"Respir Res","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jaip.2021.08.004","key":"10.1016/j.waojou.2025.101159_bib21","year":"2021","issue":"12","author":"Nolasco","volume":"9","first-page":"4371","unstructured":null,"article-title":"Benralizumab Effectiveness in Severe Eosinophilic Asthma with and without Chronic Rhinosinusitis with Nasal Polyps: A Real-World Multicenter Study","journal-title":"J Allergy Clin Immunol Pract","doi-asserted-by":"crossref"},{"DOI":null,"key":"10.1016/j.waojou.2025.101159_bib22","year":"2022","issue":"20","author":"Sposato","volume":"26","first-page":"7461","unstructured":null,"article-title":"Severe asthma and long-term Benralizumab effectiveness in real-life","journal-title":"Eur Rev Med Pharmacol Sci","doi-asserted-by":null},{"DOI":"10.1111/resp.14767","key":"10.1016/j.waojou.2025.101159_bib23","year":"2024","issue":"10","author":"Pelaia","volume":"29","first-page":"869","unstructured":null,"article-title":"Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis","journal-title":"Respirology","doi-asserted-by":"crossref"},{"DOI":"10.3390/jcm13103013","key":"10.1016/j.waojou.2025.101159_bib24","year":"2024","issue":"10","author":"Pini","volume":"13","first-page":null,"unstructured":null,"article-title":"Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study","journal-title":"J Clin Med","doi-asserted-by":"crossref"},{"DOI":"10.3390/jcm14062075","key":"10.1016/j.waojou.2025.101159_bib25","year":"2025","issue":"6","author":"Quarato","volume":"14","first-page":null,"unstructured":null,"article-title":"Long-Term Clinical Remission on Benralizumab Treatment in Severe Eosinophilic Asthma: A Four-Year Real-Life Study","journal-title":"J Clin Med","doi-asserted-by":"crossref"},{"DOI":"10.1016/S0140-6736(23)02284-5","key":"10.1016/j.waojou.2025.101159_bib26","year":"2024","issue":"10423","author":"Jackson","volume":"403","first-page":"271","unstructured":null,"article-title":"Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study","journal-title":"Lancet","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.chest.2025.04.011","key":"10.1016/j.waojou.2025.101159_bib27","year":"2025","issue":"1","author":"Pelaia","volume":"168","first-page":"19","unstructured":null,"article-title":"XALOC-1: Clinical Remission Over 2 Years With Benralizumab in Severe Eosinophilic Asthma","journal-title":"Chest","doi-asserted-by":"crossref"},{"DOI":"10.1183/13993003.01521-2023","key":"10.1016/j.waojou.2025.101159_bib28","year":"2024","issue":"1","author":"Jackson","volume":"64","first-page":null,"unstructured":null,"article-title":"Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme","journal-title":"Eur Respir J","doi-asserted-by":"crossref"},{"DOI":"10.1186/s12931-022-01952-8","key":"10.1016/j.waojou.2025.101159_bib29","year":"2022","issue":"1","author":"Menzella","volume":"23","first-page":"36","unstructured":null,"article-title":"ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study","journal-title":"Respir Res","doi-asserted-by":"crossref"},{"DOI":"10.1183/09031936.00202013","key":"10.1016/j.waojou.2025.101159_bib30","year":"2014","issue":"2","author":"Chung","volume":"43","first-page":"343","unstructured":null,"article-title":"International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma","journal-title":"Eur Respir J","doi-asserted-by":"crossref"},{"DOI":null,"key":"10.1016/j.waojou.2025.101159_bib31","year":"2024","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"10.1016/j.waojou.2025.101159_bib32","year":"2024","issue":null,"author":"Vultaggio","volume":null,"first-page":"1","unstructured":null,"article-title":"Benralizumab: from tissue distribution to eosinophilic cytotoxicity up to potential immunoregulation","journal-title":"Expert Opin Biol Ther","doi-asserted-by":null},{"DOI":"10.1016/j.waojou.2024.101016","key":"10.1016/j.waojou.2025.101159_bib33","year":"2025","issue":"1","author":"Canonica","volume":"18","first-page":null,"unstructured":null,"article-title":"Biologics as well as inhaled anti-asthmatic therapy achieve clinical remission: Evidence from the Severe Asthma Network in Italy (SANI)","journal-title":"World Allergy Organ J","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa2311155","key":"10.1016/j.waojou.2025.101159_bib34","year":"2024","issue":"10","author":"Wechsler","volume":"390","first-page":"911","unstructured":null,"article-title":"Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis","journal-title":"N Engl J Med","doi-asserted-by":"crossref"},{"DOI":"10.1067/mai.2003.1382","key":"10.1016/j.waojou.2025.101159_bib35","year":"2003","issue":"4","author":"Menzies-Gow","volume":"111","first-page":"714","unstructured":null,"article-title":"Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics","journal-title":"J Allergy Clin Immunol","doi-asserted-by":"crossref"}],"short-title":[],"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"update-policy":"https://doi.org/10.1016/elsevier_cm_policy","alternative-id":["S193945512500136X"],"article-number":"101159","content-domain":{"domain":["worldallergyorganizationjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"original-title":[],"container-title":["World Allergy Organization Journal"],"published-print":{"date-parts":[[2026,2]]},"reference-count":35,"published-online":null,"references-count":35,"short-container-title":["World Allergy Organization Journal"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1016/j.waojou.2025.101159","is_oa":true,"title":"Clinical remission in patients with severe eosinophilic asthma treated with benralizumab over 24 months: Post hoc analysis of the ANANKE study","updated":"2026-01-16T01:10:40+00:00","published_date":"2026-01-14","best_oa_location":{"url":"https://www.worldallergyorganizationjournal.org/article/S1939-4551(25)00136-X/pdf","pmh_id":null,"url_for_pdf":"https://www.worldallergyorganizationjournal.org/article/S1939-4551(25)00136-X/pdf","url_for_landing_page":"https://doi.org/10.1016/j.waojou.2025.101159"}}},"created_at":"2026-01-17T09:03:27.421Z","updated_at":"2026-01-20T15:55:50.695Z","tags":[{"paper_doi":"10.1016/j.waojou.2025.101159","tag_type":"category","value":"Allergy","value_numeric":null},{"paper_doi":"10.1016/j.waojou.2025.101159","tag_type":"condition","value":"Severe Eosinophilic Asthma","value_numeric":null},{"paper_doi":"10.1016/j.waojou.2025.101159","tag_type":"generic","value":"benralizumab","value_numeric":null},{"paper_doi":"10.1016/j.waojou.2025.101159","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1016/j.waojou.2025.101159","tag_type":"warning","value":"Design is described as a post hoc analysis; classification to a standard study design is uncertain.","value_numeric":null},{"paper_doi":"10.1016/j.waojou.2025.101159","tag_type":"warning","value":"Only title and citation details were provided; no results or numbers were available to summarize.","value_numeric":null}],"summaries":{"what_studied":"Post hoc analysis of the ANANKE study assessing clinical remission over 24 months in patients with severe eosinophilic asthma treated with benralizumab.","limitations":"Post hoc analysis of an existing study."}},{"doi":"10.1001/jamaophthalmol.2025.5594","pmid":"41505112","title":"Proteomic Profile in Retinopathy of Prematurity","journal_title":"JAMA Ophthalmology","journal_issn":"2168-6165","published_at":"2026-01-08T00:00:00.000Z","url":"https://doi.org/10.1001/jamaophthalmol.2025.5594","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-10","doi":"10.1001/jamaophthalmol.2025.5594","days":"7","issn":"2168-6165","rank":"10","field":"Clinical Medicine","score":"3","category":"Ophthalmology","categories":["Ophthalmology"],"_categories":["Ophthalmology"]},"pubmed":{"doi":"10.1001/jamaophthalmol.2025.5594","title":"Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial.","journal":"JAMA ophthalmology","methods":"","results":"A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; β = 0.68; 95% CI, 0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; β = 0.21; 95% CI, 0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome.","abstract":"$30","keywords":[],"pubmed_id":"41505112","conclusions":"","publication_date":"2026-01-08T00:00:00"},"crossref":{"DOI":"10.1001/jamaophthalmol.2025.5594","URL":"https://doi.org/10.1001/jamaophthalmol.2025.5594","ISSN":["2168-6165"],"link":[{"URL":"https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2843763/jamaophthalmology_lundgren_2026_oi_250083_1767652973.19086.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Proteomic Profile in Retinopathy of Prematurity"],"author":[{"given":"Pia","family":"Lundgren","sequence":"first","affiliation":[{"name":"The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Ophthalmology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden"}]},{"given":"Hanna","family":"Danielsson","sequence":"additional","affiliation":[{"name":"Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden"},{"name":"Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Sach’s Children’s and Youth Hospital, Södersjukhuset, Stockholm, Sweden"}]},{"given":"Mohit B.","family":"Panwar","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}]},{"given":"María Bueno","family":"Álvez","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden"}]},{"given":"Aldina","family":"Pivodic","sequence":"additional","affiliation":[{"name":"University of Gothenburg Centre for Person-Centered Care, Sahlgrenska Academy, University of Gothenburg, Sweden"}]},{"given":"Wen","family":"Zhong","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden"},{"name":"Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden"},{"name":"Science for Life Laboratory, Department of Protein Science, KTH—Royal Institute of Technology, Stockholm, Sweden"}]},{"given":"Nele","family":"Brusselaers","sequence":"additional","affiliation":[{"name":"Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden"},{"name":"Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Global Health Institute, Department of Family Medicine and Population Health, University of Antwerp, Antwerp, Belgium"}]},{"given":"Dirk","family":"Wackernagel","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany"},{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}]},{"given":"Ulrika","family":"Sjöbom","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}]},{"given":"Karin","family":"Sävman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Region Västra Götaland, Department of Neonatology, The Queen Silvia Children´s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden"}]},{"given":"Ingrid Hansen","family":"Pupp","sequence":"additional","affiliation":[{"name":"Paediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden"},{"name":"Department of Neonatology, Skåne University Hospital, Lund, Sweden"}]},{"given":"David","family":"Ley","sequence":"additional","affiliation":[{"name":"Paediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden"},{"name":"Department of Neonatology, Skåne University Hospital, Lund, Sweden"}]},{"given":"Susanna","family":"Klevebro","sequence":"additional","affiliation":[{"name":"Sach’s Children’s and Youth Hospital, Södersjukhuset, Stockholm, Sweden"},{"name":"Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden"}]},{"given":"Anders K.","family":"Nilsson","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}]},{"given":"Zhongjie","family":"Fu","sequence":"additional","affiliation":[{"name":"The Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Lois E. H.","family":"Smith","sequence":"additional","affiliation":[{"name":"The Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Mathias","family":"Uhlén","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden"},{"name":"Science for Life Laboratory, Department of Protein Science, KTH—Royal Institute of Technology, Stockholm, Sweden"}]},{"given":"Ann","family":"Hellström","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Ophthalmology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden"}]}],"issued":{"date-parts":[[2026,1,8]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":null,"created":{"date-time":"2026-01-08T16:00:46Z","timestamp":1767888046000,"date-parts":[[2026,1,8]]},"indexed":{"date-time":"2026-01-08T20:41:06Z","timestamp":1767904866836,"date-parts":[[2026,1,8]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2843763"}},"subtitle":["A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial"],"deposited":{"date-time":"2026-01-08T16:00:52Z","timestamp":1767888052000,"date-parts":[[2026,1,8]]},"issn-type":[{"type":"print","value":"2168-6165"}],"published":{"date-parts":[[2026,1,8]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.1007/s00431-024-05450-5","key":"eoi250083r1","year":"2024","issue":"4","author":"Chen","volume":"183","first-page":"1891","unstructured":null,"article-title":"Visual impairment burden in retinopathy of prematurity: trends, inequalities, and improvement gaps.","journal-title":"Eur J Pediatr","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.survophthal.2018.04.002","key":"eoi250083r2","year":"2018","issue":"5","author":"Kim","volume":"63","first-page":"618","unstructured":null,"article-title":"Retinopathy of prematurity: a review of risk factors and their clinical significance.","journal-title":"Surv Ophthalmol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.survophthal.2022.11.007","key":"eoi250083r3","year":"2023","issue":"2","author":"Fevereiro-Martins","volume":"68","first-page":"175","unstructured":null,"article-title":"Retinopathy of prematurity: a review of pathophysiology and signaling pathways.","journal-title":"Surv Ophthalmol","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamapediatrics.2020.5653","key":"eoi250083r4","year":"2021","issue":"4","author":"Hellström","volume":"175","first-page":"359","unstructured":null,"article-title":"Effect of enteral lipid supplement on severe retinopathy of prematurity: a randomized clinical trial.","journal-title":"JAMA Pediatr","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamanetworkopen.2021.28771","key":"eoi250083r5","year":"2021","issue":"10","author":"Hellström","volume":"4","first-page":null,"unstructured":null,"article-title":"Association of docosahexaenoic acid and arachidonic acid serum levels with retinopathy of prematurity in preterm infants.","journal-title":"JAMA Netw Open","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.clnu.2024.03.031","key":"eoi250083r6","year":"2024","issue":"5","author":"Klevebro","volume":"43","first-page":"1162","unstructured":null,"article-title":"Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants.","journal-title":"Clin Nutr","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41390-024-03775-3","key":"eoi250083r7","year":"2025","issue":"2","author":"Lundgren","volume":"98","first-page":"680","unstructured":null,"article-title":"Platelet characteristics in extremely preterm infants after fatty acid supplementation: a randomized controlled trial.","journal-title":"Pediatr Res","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41390-020-0912-8","key":"eoi250083r8","year":"2021","issue":"3","author":"Zhong","volume":"89","first-page":"604","unstructured":null,"article-title":"Dramatic changes in blood protein levels during the first week of life in extremely preterm infants.","journal-title":"Pediatr Res","doi-asserted-by":"crossref"},{"DOI":"10.1001/archopht.121.12.1684","key":"eoi250083r9","year":"2003","issue":"12","author":"Early Treatment For Retinopathy Of Prematurity Cooperative Group","volume":"121","first-page":"1684","unstructured":null,"article-title":"Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.","journal-title":"Arch Ophthalmol","doi-asserted-by":"crossref"},{"DOI":"10.1001/archopht.123.7.991","key":"eoi250083r10","year":"2005","issue":"7","author":"International Committee for the Classification of Retinopathy of Prematurity","volume":"123","first-page":"991","unstructured":null,"article-title":"The International Classification of Retinopathy of Prematurity revisited.","journal-title":"Arch Ophthalmol","doi-asserted-by":"crossref"},{"DOI":"10.1371/journal.pone.0095192","key":"eoi250083r11","year":"2014","issue":"4","author":"Assarsson","volume":"9","first-page":null,"unstructured":null,"article-title":"Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability.","journal-title":"PLoS One","doi-asserted-by":"crossref"},{"DOI":"10.1093/bioinformatics/btac757","key":"eoi250083r12","year":"2023","issue":"1","author":"Fang","volume":"39","first-page":null,"unstructured":null,"article-title":"GSEApy: a comprehensive package for performing gene set enrichment analysis in Python.","journal-title":"Bioinformatics","doi-asserted-by":"crossref"},{"DOI":"10.1164/rccm.201812-2348OC","key":"eoi250083r13","year":"2019","issue":"6","author":"Jensen","volume":"200","first-page":"751","unstructured":null,"article-title":"The diagnosis of bronchopulmonary dysplasia in very preterm infants: an evidence-based approach.","journal-title":"Am J Respir Crit Care Med","doi-asserted-by":"crossref"},{"DOI":"10.1111/apa.12478","key":"eoi250083r14","year":"2014","issue":"2","author":"Kistner","volume":"103","first-page":"149","unstructured":null,"article-title":"Neonatal IGF-1/IGFBP-1 axis and retinopathy of prematurity are associated with increased blood pressure in preterm children.","journal-title":"Acta Paediatr","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41598-021-86302-2","key":"eoi250083r15","year":"2021","issue":"1","author":"Patnaik","volume":"11","first-page":"7444","unstructured":null,"article-title":"An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina.","journal-title":"Sci Rep","doi-asserted-by":"crossref"},{"DOI":"10.3390/ijms242015309","key":"eoi250083r16","year":"2023","issue":"20","author":"Choreziak-Michalak","volume":"24","first-page":"15309","unstructured":null,"article-title":"Comprehensive Analysis of the role of gene variants in matrix metalloproteinases and their tissue inhibitors in retinopathy of prematurity: a study in the Polish population.","journal-title":"Int J Mol Sci","doi-asserted-by":"crossref"},{"DOI":"10.1203/00006450-200112000-00017","key":"eoi250083r17","year":"2001","issue":"6","author":"Hikino","volume":"50","first-page":"732","unstructured":null,"article-title":"Physical growth and retinopathy in preterm infants: involvement of IGF-I and GH.","journal-title":"Pediatr Res","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.celrep.2017.01.014","key":"eoi250083r18","year":"2017","issue":"7","author":"Fu","volume":"18","first-page":"1606","unstructured":null,"article-title":"FGF21 administration suppresses retinal and choroidal neovascularization in mice.","journal-title":"Cell Rep","doi-asserted-by":"crossref"},{"DOI":"10.1007/s10456-023-09872-x","key":"eoi250083r19","year":"2023","issue":"3","author":"Fu","volume":"26","first-page":"409","unstructured":null,"article-title":"FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP.","journal-title":"Angiogenesis","doi-asserted-by":"crossref"},{"DOI":"10.3390/ijms21041188","key":"eoi250083r20","year":"2020","issue":"4","author":"Tomita","volume":"21","first-page":"1188","unstructured":null,"article-title":"Long-acting FGF21 inhibits retinal vascular leakage in in vivo and in vitro models.","journal-title":"Int J Mol Sci","doi-asserted-by":"crossref"},{"DOI":"10.1167/iovs.19-27258","key":"eoi250083r21","year":"2019","issue":"12","author":"Park","volume":"60","first-page":"3813","unstructured":null,"article-title":"Immune and inflammatory proteins in cord blood as predictive biomarkers of retinopathy of prematurity in preterm infants.","journal-title":"Invest Ophthalmol Vis Sci","doi-asserted-by":"crossref"},{"DOI":"10.1167/iovs.17-21931","key":"eoi250083r22","year":"2017","issue":"14","author":"Holm","volume":"58","first-page":"6419","unstructured":null,"article-title":"Systemic inflammation-associated proteins and retinopathy of prematurity in infants born before the 28th week of gestation.","journal-title":"Invest Ophthalmol Vis Sci","doi-asserted-by":"crossref"},{"DOI":"10.1146/annurev-physiol-021115-105339","key":"eoi250083r23","year":"2016","issue":null,"author":"Fisher","volume":"78","first-page":"223","unstructured":null,"article-title":"Understanding the physiology of FGF21.","journal-title":"Annu Rev Physiol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.redox.2016.12.024","key":"eoi250083r24","year":"2017","issue":null,"author":"Gómez-Sámano","volume":"11","first-page":"335","unstructured":null,"article-title":"Fibroblast growth factor 21 and its novel association with oxidative stress.","journal-title":"Redox Biol","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41598-021-00906-2","key":"eoi250083r25","year":"2022","issue":"1","author":"Li","volume":"12","first-page":"400","unstructured":null,"article-title":"Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis.","journal-title":"Sci Rep","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.yexcr.2025.114417","key":"eoi250083r26","year":"2025","issue":"1","author":"Lin","volume":"445","first-page":null,"unstructured":null,"article-title":"RhFGF21 protected PC12 cells against mitochondrial apoptosis triggered by H2O2 via the AKT-mediated ROS signaling pathway.","journal-title":"Exp Cell Res","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.intimp.2016.05.026","key":"eoi250083r27","year":"2016","issue":null,"author":"Yu","volume":"38","first-page":"144","unstructured":null,"article-title":"Fibroblast growth factor 21 (FGF21) inhibits macrophage-mediated inflammation by activating Nrf2 and suppressing the NF-?B signaling pathway.","journal-title":"Int Immunopharmacol","doi-asserted-by":"crossref"},{"DOI":"10.3389/fendo.2023.1105602","key":"eoi250083r28","year":"2023","issue":null,"author":"Mistry","volume":"14","first-page":null,"unstructured":null,"article-title":"The crosstalk between FGF21 and GH leads to weakened GH receptor signaling and IGF1 expression and is associated with growth failure in very preterm infants.","journal-title":"Front Endocrinol (Lausanne)","doi-asserted-by":"crossref"},{"DOI":"10.1542/peds.112.5.1016","key":"eoi250083r29","year":"2003","issue":"5","author":"Hellström","volume":"112","first-page":"1016","unstructured":null,"article-title":"Postnatal serum insulinlike growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth.","journal-title":"Pediatrics","doi-asserted-by":"crossref"},{"DOI":"10.1542/peds.2008-2697","key":"eoi250083r30","year":"2009","issue":"4","author":"Hellström","volume":"123","first-page":"e638","unstructured":null,"article-title":"Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening.","journal-title":"Pediatrics","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jhep.2013.09.003","key":"eoi250083r31","year":"2014","issue":"1","author":"Mutanen","volume":"60","first-page":"183","unstructured":null,"article-title":"Serum FGF21 increases with hepatic fat accumulation in pediatric onset intestinal failure.","journal-title":"J Hepatol","doi-asserted-by":"crossref"},{"DOI":"10.1515/cclm-2018-0914","key":"eoi250083r32","year":"2019","issue":"5","author":"Siahanidou","volume":"57","first-page":"e83","unstructured":null,"article-title":"Association of fibroblast growth factor 21 plasma levels with neonatal sepsis: preliminary results.","journal-title":"Clin Chem Lab Med","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.cyto.2018.05.020","key":"eoi250083r33","year":"2018","issue":null,"author":"Li","volume":"111","first-page":"428","unstructured":null,"article-title":"Early increases in serum FGF21 levels predict mortality of septic patients.","journal-title":"Cytokine","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.ymgme.2021.12.001","key":"eoi250083r34","year":"2022","issue":"1","author":"Riley","volume":"135","first-page":"63","unstructured":null,"article-title":"FGF21 outperforms GDF15 as a diagnostic biomarker of mitochondrial disease in children.","journal-title":"Mol Genet Metab","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.arcped.2018.02.005","key":"eoi250083r35","year":"2018","issue":"4","author":"Darmaun","volume":"25","first-page":"286","unstructured":null,"article-title":"Parenteral nutrition for preterm infants: issues and strategy.","journal-title":"Arch Pediatr","doi-asserted-by":"crossref"},{"DOI":"10.3390/antiox10111672","key":"eoi250083r36","year":"2021","issue":"11","author":"Lembo","volume":"10","first-page":"1672","unstructured":null,"article-title":"Oxidative stress in preterm newborns.","journal-title":"Antioxidants (Basel)","doi-asserted-by":"crossref"},{"DOI":"10.3945/ajcn.114.099291","key":"eoi250083r37","year":"2015","issue":"4","author":"Fu","volume":"101","first-page":"879","unstructured":null,"article-title":"Dietary ?-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin.","journal-title":"Am J Clin Nutr","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.freeradbiomed.2019.02.020","key":"eoi250083r38","year":"2019","issue":null,"author":"Lavoie","volume":"142","first-page":"155","unstructured":null,"article-title":"Parenteral nutrition and oxidant stress in the newborn: a narrative review.","journal-title":"Free Radic Biol Med","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.clp.2016.04.001","key":"eoi250083r39","year":"2016","issue":"3","author":"Morton","volume":"43","first-page":"395","unstructured":null,"article-title":"Fetal physiology and the transition to extrauterine life.","journal-title":"Clin Perinatol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.freeradbiomed.2019.03.035","key":"eoi250083r40","year":"2019","issue":null,"author":"Perez","volume":"142","first-page":"61","unstructured":null,"article-title":"Oxygen radical disease in the newborn, revisited: oxidative stress and disease in the newborn period.","journal-title":"Free Radic Biol Med","doi-asserted-by":"crossref"},{"DOI":"10.3389/fped.2016.00143","key":"eoi250083r41","year":"2017","issue":null,"author":"Perrone","volume":"4","first-page":"143","unstructured":null,"article-title":"Oxygen use in neonatal care: a 2-edged sword.","journal-title":"Front Pediatr","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.clnu.2023.04.020","key":"eoi250083r42","year":"2023","issue":"6","author":"Sjöbom","volume":"42","first-page":"962","unstructured":null,"article-title":"Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial.","journal-title":"Clin Nutr","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamaophthalmol.2023.2336","key":"eoi250083r43","year":"2023","issue":"8","author":"Pivodic","volume":"141","first-page":"716","unstructured":null,"article-title":"Prognostic value of parenteral nutrition duration on risk of retinopathy of prematurity: development and validation of the revised DIGIROP clinical decision support tool.","journal-title":"JAMA Ophthalmol","doi-asserted-by":"crossref"},{"DOI":"10.1136/archdischild-2014-306816","key":"eoi250083r44","year":"2016","issue":"2","author":"Stoltz Sjöström","volume":"101","first-page":"F108","unstructured":null,"article-title":"Low energy intake during the first 4 weeks of life increases the risk for severe retinopathy of prematurity in extremely preterm infants.","journal-title":"Arch Dis Child Fetal Neonatal Ed","doi-asserted-by":"crossref"},{"DOI":"10.1542/peds.2015-2372","key":"eoi250083r45","year":"2015","issue":"6","author":"Zhou","volume":"136","first-page":"e1576","unstructured":null,"article-title":"Human milk feeding as a protective factor for retinopathy of prematurity: a meta-analysis.","journal-title":"Pediatrics","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.cyto.2012.10.014","key":"eoi250083r46","year":"2013","issue":"1","author":"Bose","volume":"61","first-page":"315","unstructured":null,"article-title":"Systemic inflammation associated with mechanical ventilation among extremely preterm infants.","journal-title":"Cytokine","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.cellimm.2021.104451","key":"eoi250083r47","year":"2022","issue":null,"author":"Seillier","volume":"371","first-page":null,"unstructured":null,"article-title":"Roles of the tissue-type plasminogen activator in immune response.","journal-title":"Cell Immunol","doi-asserted-by":"crossref"},{"DOI":"10.1542/peds.89.1.43","key":"eoi250083r48","year":"1992","issue":"1","author":"Corrigan","volume":"89","first-page":"43","unstructured":null,"article-title":"Tissue-type plasminogen activator, plasminogen activator inhibitor, and histidine-rich glycoproteins in stressed human newborns.","journal-title":"Pediatrics","doi-asserted-by":"crossref"},{"DOI":"10.1111/j.1651-2227.1997.tb14816.x","key":"eoi250083r49","year":"1997","issue":"10","author":"Mautone","volume":"86","first-page":"1100","unstructured":null,"article-title":"Coagulation and fibrinolytic systems in the ill preterm newborn.","journal-title":"Acta Paediatr","doi-asserted-by":"crossref"},{"DOI":"10.3390/ijms23010337","key":"eoi250083r50","year":"2021","issue":"1","author":"Ismail","volume":"23","first-page":"337","unstructured":null,"article-title":"The plasminogen-activator plasmin system in physiological and pathophysiological angiogenesis.","journal-title":"Int J Mol Sci","doi-asserted-by":"crossref"},{"DOI":"10.1172/jci.insight.99448","key":"eoi250083r51","year":"2018","issue":"19","author":"Cakir","volume":"3","first-page":null,"unstructured":null,"article-title":"Thrombocytopenia is associated with severe retinopathy of prematurity.","journal-title":"JCI Insight","doi-asserted-by":"crossref"},{"DOI":"10.1159/000448161","key":"eoi250083r52","year":"2017","issue":"1","author":"Lundgren","volume":"111","first-page":"79","unstructured":null,"article-title":"Aggressive posterior retinopathy of prematurity is associated with multiple infectious episodes and thrombocytopenia.","journal-title":"Neonatology","doi-asserted-by":"crossref"},{"DOI":"10.1167/iovs.16-19653","key":"eoi250083r53","year":"2016","issue":"11","author":"Lynch","volume":"57","first-page":"5076","unstructured":null,"article-title":"The relationship of novel plasma proteins in the early neonatal period with retinopathy of prematurity.","journal-title":"Invest Ophthalmol Vis Sci","doi-asserted-by":"crossref"},{"DOI":"10.1203/PDR.0b013e3181d01a36","key":"eoi250083r54","year":"2010","issue":"4","author":"Sood","volume":"67","first-page":"394","unstructured":null,"article-title":"Perinatal systemic inflammatory response syndrome and retinopathy of prematurity.","journal-title":"Pediatr Res","doi-asserted-by":"crossref"},{"DOI":"10.1167/tvst.9.13.14","key":"eoi250083r55","year":"2020","issue":"13","author":"Markasz","volume":"9","first-page":"14","unstructured":null,"article-title":"Cluster analysis of early postnatal biochemical markers may predict development of retinopathy of prematurity.","journal-title":"Transl Vis Sci Technol","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41390-021-01528-0","key":"eoi250083r56","year":"2022","issue":"4","author":"Danielsson","volume":"91","first-page":"937","unstructured":null,"article-title":"Blood protein profiles related to preterm birth and retinopathy of prematurity.","journal-title":"Pediatr Res","doi-asserted-by":"crossref"}],"short-title":[],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Ophthalmology"],"reference-count":56,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,8]]},"references-count":56,"short-container-title":["JAMA Ophthalmol"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1001/jamaophthalmol.2025.5594","is_oa":true,"title":"Proteomic Profile in Retinopathy of Prematurity","updated":"2026-01-13T16:36:47+00:00","published_date":"2026-01-08","best_oa_location":{"url":"https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2843763/jamaophthalmology_lundgren_2026_oi_250083_1767652973.19086.pdf","pmh_id":null,"url_for_pdf":"https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2843763/jamaophthalmology_lundgren_2026_oi_250083_1767652973.19086.pdf","url_for_landing_page":"https://doi.org/10.1001/jamaophthalmol.2025.5594"}}},"created_at":"2026-01-15T20:51:27.064Z","updated_at":"2026-01-17T09:03:27.421Z","tags":[{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"age_group","value":"neonate","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"condition","value":"Retinopathy Of Prematurity","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"generic","value":"arachidonic acid","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"generic","value":"docosahexaenoic acid","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"modality","value":"Nutritional Supplement","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"sample_size","value":"n=177","value_numeric":177},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"warning","value":"Design label is non-standard: this is a post hoc exploratory proteomic analysis within an RCT, not a randomized comparison for these outcomes.","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"warning","value":"Generalizability may be limited to similar tertiary neonatal settings in Sweden.","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.5594","tag_type":"warning","value":"Reported β coefficients are from mixed-effects models and do not translate directly to absolute risk differences.","value_numeric":null}],"summaries":{"what_studied":"Exploratory, post hoc longitudinal proteomics of 177 extremely preterm infants (<28 weeks’ GA) from the MDM randomized trial assessed whether early (first month) serum protein trajectories were associated with later severe ROP and whether AA/DHA supplementation (100/50 mg/kg/day) altered the proteome.","key_result":"Severe ROP occurred in 50/177 (28.2%); 109 of 538 proteins showed first‑month profiles associated with severe ROP, with the strongest early rises in FGF‑21 (β=0.68; 95% CI, 0.39-0.97; Q=0.002) and tPA (β=0.21; 95% CI, 0.13-0.29; Q<0.001). Early‑week FGF‑21 increases correlated with lower GA, lower birth weight, low enteral energy intake, and more days on mechanical ventilation, and AA/DHA supplementation showed no association with the proteome.","limitations":"Post hoc, exploratory analysis within an RCT limits causal inference for proteomic associations; findings are from three centers in Sweden and may not generalize beyond this setting."}},{"doi":"10.2215/cjn.0000000948","pmid":"41433094","title":"Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial","journal_title":"Clinical Journal of the American Society of Nephrology","journal_issn":"1555-9041","published_at":"2025-12-23T00:00:00.000Z","url":"https://doi.org/10.2215/cjn.0000000948","source_score":31,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-24","doi":"10.2215/cjn.0000000948","days":"30","issn":"1555-9041","rank":"5","field":"Clinical Medicine","score":"31","category":"Urology & Nephrology","categories":["Urology & Nephrology"],"_categories":["Urology & Nephrology"]},"pubmed":{"doi":"10.2215/CJN.0000000948","title":"Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial.","journal":"Clinical journal of the American Society of Nephrology : CJASN","methods":"","results":"Next-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints.","abstract":"$32","keywords":[],"pubmed_id":"41433094","conclusions":"","publication_date":"2025-12-23T00:00:00"},"crossref":{"DOI":"10.2215/cjn.0000000948","URL":"https://doi.org/10.2215/cjn.0000000948","ISSN":["1555-9041","1555-905X"],"link":[{"URL":"https://journals.lww.com/10.2215/CJN.0000000948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial"],"author":[{"given":"Jennifer","family":"Yee","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA"}]},{"given":"Wu","family":"Gong","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Jula","family":"Inrig","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Michelle N","family":"Rheault","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA"}]},{"given":"Angela J","family":"Gruber","sequence":"additional","affiliation":[{"name":"PreventionGenetics, Marshfield, WI, USA"}]},{"given":"Patricia W","family":"Bedard","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Radko","family":"Komers","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Howard","family":"Trachtman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA"}]}],"issued":{"date-parts":[[2025,12,23]]},"member":"276","prefix":"10.2215","source":"Crossref","volume":null,"created":{"date-time":"2025-12-23T17:00:44Z","timestamp":1766509244000,"date-parts":[[2025,12,23]]},"indexed":{"date-time":"2025-12-23T17:18:17Z","timestamp":1766510297847,"date-parts":[[2025,12,23]]},"license":[{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000,"date-parts":[[2025,12,23]]},"delay-in-days":0,"content-version":"unspecified"}],"subject":[],"abstract":"$33","language":"en","relation":{},"resource":{"primary":{"URL":"https://journals.lww.com/10.2215/CJN.0000000948"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","value":"2025-06-26"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","value":"2025-12-18"}],"deposited":{"date-time":"2025-12-23T17:00:44Z","timestamp":1766509244000,"date-parts":[[2025,12,23]]},"issn-type":[{"type":"print","value":"1555-9041"},{"type":"electronic","value":"1555-905X"}],"published":{"date-parts":[[2025,12,23]]},"publisher":"Ovid Technologies (Wolters Kluwer Health)","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1097/lww.0000000000001000","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Clinical Journal of the American Society of Nephrology"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,12,23]]},"references-count":0,"short-container-title":["CJASN"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.2215/cjn.0000000948","is_oa":true,"title":"Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial","updated":"2025-12-24T00:55:44+00:00","published_date":"2025-12-23","best_oa_location":{"url":"https://doi.org/10.2215/cjn.0000000948","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.2215/cjn.0000000948"}}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-21T12:05:26.220Z","tags":[{"paper_doi":"10.2215/cjn.0000000948","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"condition","value":"Focal Segmental Glomerulosclerosis","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"generic","value":"irbesartan","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"generic","value":"sparsentan","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"modality","value":"Angiotensin Receptor Blocker","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"modality","value":"Dual Endothelin Angiotensin Receptor Antagonist","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"No numeric effect sizes or event counts were provided in the abstract.","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"Results are from an exploratory post hoc subgroup analysis of an RCT.","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"Subgroup counts may overlap; total N for genetic FSGS was not specified.","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"Timeframe for subgroup outcomes was not explicitly stated.","value_numeric":null}],"summaries":{"what_studied":"Post hoc, exploratory analysis of DUPLEX evaluated sparsentan versus irbesartan in participants with genetic-associated FSGS, including podocyte gene variants (n=31), COL4A3-5 variants (n=25), and APOL1 high-risk genotypes (n=14).","key_result":"Sparsentan produced substantial, sustained reductions in proteinuria, with numerically more complete remissions versus irbesartan, and a lower proportion reached composite kidney endpoints; no effect sizes were reported.","limitations":"Post hoc exploratory design with small genetic subgroups; baseline differences between groups (younger in the podocyte-variant group; more African American participants in the APOL1 group) may confound results.","practice_takeaway":"Findings support an antiproteinuric benefit of sparsentan in genetic FSGS, consistent with DUPLEX overall, but conclusions should be cautious due to exploratory subgroup analysis and small numbers."}},{"doi":"10.1136/thorax-2025-223282","pmid":"41402044","title":"Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial","journal_title":"Thorax","journal_issn":"0040-6376","published_at":"2025-12-17T00:00:00.000Z","url":"https://doi.org/10.1136/thorax-2025-223282","source_score":29,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-12-20","doi":"10.1136/thorax-2025-223282","days":"30","issn":"0040-6376","rank":"1","field":"Clinical Medicine","score":"29","category":"Respiratory System","categories":["Respiratory System"],"_categories":["Respiratory System"]},"pubmed":{"doi":"10.1136/thorax-2025-223282","title":"Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial.","journal":"Thorax","methods":"","results":"Discontinuing LAMA was associated with a marked, transient increase in moderate-to-severe exacerbations during the first versus subsequent quarters (p=0.001; rate ratio up to 2.2 (95% CI 1.2 to 4.1) in the subgroup least influenced by concomitant ICS use). This observation was not confirmed for severe exacerbations, likely due to low event count. In contrast, discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), though the difference for moderate-to-severe events did not reach statistical significance. Importantly, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count.","abstract":"$34","keywords":["COPD Exacerbations","COPD Pharmacology"],"pubmed_id":"41402044","conclusions":"Our findings suggest potent LAMA and ICS treatment withdrawal effects on exacerbations, highlighting the importance of treatment adherence and accounting for withdrawal effects in clinical trials.","publication_date":"2025-12-17T00:00:00"},"crossref":{"DOI":"10.1136/thorax-2025-223282","URL":"https://doi.org/10.1136/thorax-2025-223282","ISSN":["0040-6376","1468-3296"],"link":[{"URL":"https://syndication.highwire.org/content/doi/10.1136/thorax-2025-223282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"thorax-2025-223282","type":"journal-article","issue":null,"score":1,"title":["Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial"],"author":[{"given":"Alexander G","family":"Mathioudakis","sequence":"first","affiliation":[{"name":"Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"},{"name":"North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, England, UK"}]},{"given":"Sebastian","family":"Bate","sequence":"additional","affiliation":[{"name":"Research and Innovation, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"},{"name":"Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care, Facutly of Biology, Medicine and Health, The University of Manchester, Manchester, UK"}]},{"given":"Victoria","family":"Chatzimavridou-Grigoriadou","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"}]},{"given":"Pradeesh","family":"Sivapalan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Capital Region of Denmark, Denmark"}]},{"given":"Jens-Ulrik Stæhr","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Capital Region of Denmark, Denmark"}]},{"given":"Nawar Diar","family":"Bakerly","sequence":"additional","affiliation":[{"name":"Respiratory Medicine, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK"}]},{"given":"Jørgen","family":"Vestbo","sequence":"additional","affiliation":[{"name":"Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"},{"name":"Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"},{"name":"North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, England, UK"},{"name":"Medicines Evaluation Unit an IQVIA business, Wythenshawe, UK"}]}],"funder":[{"id":[{"id":"10.13039/501100000659","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100000659","name":"Research Trainees Coordinating Centre","award":["CL-2021-06-007"],"award-info":[{"award-number":["CL-2021-06-007"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/100014653","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100014653","name":"Manchester Biomedical Research Centre","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"doi-asserted-by":"publisher"},{"name":"Pickering Fellowship, North West Lung Centre Charity","award":["No award/grant number"],"award-info":[{"award-number":["No award/grant number"]}]}],"issued":{"date-parts":[[2025,12,15]]},"member":"239","prefix":"10.1136","source":"Crossref","volume":null,"created":{"date-time":"2025-12-16T07:25:21Z","timestamp":1765869921000,"date-parts":[[2025,12,16]]},"indexed":{"date-time":"2025-12-16T07:30:15Z","timestamp":1765870215677,"date-parts":[[2025,12,16]]},"subject":[],"abstract":"$35","accepted":{"date-parts":[[2025,11,11]]},"language":"en","relation":{},"resource":{"primary":{"URL":"https://thorax.bmj.com/lookup/doi/10.1136/thorax-2025-223282"}},"subtitle":[],"deposited":{"date-time":"2025-12-16T07:25:28Z","timestamp":1765869928000,"date-parts":[[2025,12,16]]},"issn-type":[{"type":"print","value":"0040-6376"},{"type":"electronic","value":"1468-3296"}],"published":{"date-parts":[[2025,12,15]]},"publisher":"BMJ","reference":[{"DOI":"10.1016/S0140-6736(24)00367-2","key":"2025121523251543000_thorax-2025-223282v1.1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Collaborators GBDCoD . Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2024;2100–32. doi:10.1016/S0140-6736(24)00367-2","article-title":null,"journal-title":null,"doi-asserted-by":"crossref"},{"DOI":"10.1016/S0140-6736(24)00757-8","key":"2025121523251543000_thorax-2025-223282v1.2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Diseases GBD, Injuries C . Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2024;2133–61. doi:10.1016/S0140-6736(24)00757-8","article-title":null,"journal-title":null,"doi-asserted-by":"crossref"},{"DOI":"10.1183/13993003.00239-2023","key":"2025121523251543000_thorax-2025-223282v1.3","year":"2023","issue":null,"author":"Agustí","volume":"61","first-page":null,"unstructured":null,"article-title":"Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary","journal-title":"Eur Respir J","doi-asserted-by":"crossref"},{"DOI":"10.1183/20734735.0267-2022","key":"2025121523251543000_thorax-2025-223282v1.4","year":"2023","issue":null,"author":"Stolz","volume":"19","first-page":null,"unstructured":null,"article-title":"Current and future developments in the pharmacology of asthma and COPD: ERS seminar, Naples 2022","journal-title":"Breathe (Sheff)","doi-asserted-by":"crossref"},{"DOI":"10.1183/13993003.01655-2017","key":"2025121523251543000_thorax-2025-223282v1.5","year":"2017","issue":null,"author":"Agustí","volume":"50","first-page":null,"unstructured":null,"article-title":"Precision medicine in airway diseases: moving to clinical practice","journal-title":"Eur Respir J","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.ccm.2020.05.005","key":"2025121523251543000_thorax-2025-223282v1.6","year":"2020","issue":null,"author":"Mathioudakis","volume":"41","first-page":"463","unstructured":null,"article-title":"Long-Acting Bronchodilators for Chronic Obstructive Pulmonary Disease: Which One(S), How, and When?","journal-title":"Clin Chest Med","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.chest.2024.06.3790","key":"2025121523251543000_thorax-2025-223282v1.7","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1183/13993003.02119-2019","key":"2025121523251543000_thorax-2025-223282v1.8","year":"2020","issue":null,"author":"Mathioudakis","volume":"55","first-page":"32108044","unstructured":null,"article-title":"Change in blood eosinophils following treatment with inhaled corticosteroids may predict long-term clinical response in COPD","journal-title":"Eur Respir J","doi-asserted-by":"crossref"},{"DOI":"10.1183/20734735.0260-2022","key":"2025121523251543000_thorax-2025-223282v1.9","year":"2023","issue":null,"author":"Soumagne","volume":"19","first-page":null,"unstructured":null,"article-title":"Impact of triple therapy on mortality in COPD","journal-title":"Breathe (Sheff)","doi-asserted-by":"crossref"},{"DOI":"10.1016/S2213-2600(18)30006-7","key":"2025121523251543000_thorax-2025-223282v1.10","year":"2018","issue":null,"author":"Bafadhel","volume":"6","first-page":"117","unstructured":null,"article-title":"Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials","journal-title":"Lancet Respir Med","doi-asserted-by":"crossref"},{"DOI":"10.1183/09031936.00098307","key":"2025121523251543000_thorax-2025-223282v1.11","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/j.1752-699X.2010.00198.x","key":"2025121523251543000_thorax-2025-223282v1.12","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1183/09059180.05.00009604","key":"2025121523251543000_thorax-2025-223282v1.13","year":"2005","issue":null,"author":"Rand","volume":"14","first-page":"97","unstructured":null,"article-title":"Patient adherence with COPD therapy","journal-title":"Eur Respir Rev","doi-asserted-by":"crossref"},{"DOI":"10.3390/ijerph191811573","key":"2025121523251543000_thorax-2025-223282v1.14","year":"2022","issue":null,"author":"Homętowska","volume":"19","first-page":null,"unstructured":null,"article-title":"Treatment Adherence in Patients with Obstructive Pulmonary Diseases","journal-title":"Int J Environ Res Public Health","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.pec.2024.108465","key":"2025121523251543000_thorax-2025-223282v1.15","year":"2025","issue":null,"author":"Liu","volume":"130","first-page":"108465","unstructured":null,"article-title":"Path analysis of illness perception, medication beliefs, family support on inhaler adherence in elderly COPD patients: Based on triadic reciprocal determinism","journal-title":"Patient Educ Couns","doi-asserted-by":"crossref"},{"DOI":"10.2147/COPD.S460903","key":"2025121523251543000_thorax-2025-223282v1.16","year":"2024","issue":null,"author":"Vogelmeier","volume":"19","first-page":"1835","unstructured":null,"article-title":"Evaluation of Adherence and Persistence to Triple Therapy in Patients with COPD: A German Claims Data Study","journal-title":"Int J Chron Obstruct Pulmon Dis","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa1516385","key":"2025121523251543000_thorax-2025-223282v1.17","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1177/17534666221107314","key":"2025121523251543000_thorax-2025-223282v1.18","year":"2022","issue":null,"author":"Singh","volume":"16","first-page":"17534666221107314","unstructured":null,"article-title":"Predictive modeling of COPD exacerbation rates using baseline risk factors","journal-title":"Ther Adv Respir Dis","doi-asserted-by":"crossref"},{"DOI":"10.1136/thorax-2024-222547","key":"2025121523251543000_thorax-2025-223282v1.19","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1183/13993003.00351-2020","key":"2025121523251543000_thorax-2025-223282v1.20","year":"2020","issue":null,"author":"Chalmers","volume":"55","first-page":"32366483","unstructured":null,"article-title":"Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline","journal-title":"Eur Respir J","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa1407154","key":"2025121523251543000_thorax-2025-223282v1.21","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S2213-2600(16)00100-4","key":"2025121523251543000_thorax-2025-223282v1.22","year":"2016","issue":null,"author":"Watz","volume":"4","first-page":"390","unstructured":null,"article-title":"Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial","journal-title":"Lancet Respir Med","doi-asserted-by":"crossref"},{"DOI":"10.1164/rccm.201803-0405OC","key":"2025121523251543000_thorax-2025-223282v1.23","year":"2018","issue":null,"author":"Chapman","volume":"198","first-page":"329","unstructured":null,"article-title":"Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial","journal-title":"Am J Respir Crit Care Med","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa1715275","key":"2025121523251543000_thorax-2025-223282v1.24","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa1901963","key":"2025121523251543000_thorax-2025-223282v1.25","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"}],"short-title":[],"update-policy":"https://doi.org/10.1136/crossmarkpolicy","alternative-id":["10.1136/thorax-2025-223282"],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Thorax"],"reference-count":25,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,12,15]]},"references-count":25,"clinical-trial-number":[{"registry":"10.18810/clinical-trials-gov","clinical-trial-number":"nct01782326"}],"short-container-title":["Thorax"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1136/thorax-2025-223282","is_oa":false,"title":"Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial","updated":"2025-12-17T23:50:37+00:00","published_date":"2025-12-15","best_oa_location":null}},"created_at":"2026-01-17T09:03:27.421Z","updated_at":"2026-01-19T09:31:36.873Z","tags":[{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"condition","value":"Chronic Obstructive Pulmonary Disease","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"generic","value":"fluticasone","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"generic","value":"glycopyrronium","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"generic","value":"indacaterol","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"generic","value":"salmeterol","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"modality","value":"Inhaled Corticosteroid","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"modality","value":"LAMA","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"sample_size","value":"n=3362","value_numeric":3362},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"warning","value":"Design is a post hoc analysis of a randomized trial; withdrawal effects are inferred rather than randomized.","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"warning","value":"Severe exacerbation findings, particularly for LAMA discontinuation, were limited by low event counts.","value_numeric":null},{"paper_doi":"10.1136/thorax-2025-223282","tag_type":"warning","value":"The rate ratio (up to 2.2) was reported for a subgroup least influenced by concomitant ICS; applicability to all patients may differ.","value_numeric":null}],"summaries":{"what_studied":"Post hoc analysis of the 52-week FLAME randomized trial (n=3362) in moderate-to-severe COPD with prior exacerbations assessed whether stopping LAMA or ICS increased exacerbations during the first quarter (first 3 months) versus later quarters, stratified by baseline use.","key_result":"Stopping LAMA increased moderate-to-severe exacerbations in the first vs subsequent quarters (p=0.001; rate ratio up to 2.2, 95% CI 1.2–4.1 in the subgroup least influenced by concomitant ICS), without a confirmed signal for severe events. Stopping ICS produced an early rise in severe exacerbations (p=0.023), with no statistically significant difference for moderate-to-severe events; this effect did not vary by baseline blood eosinophil count.","limitations":"Post hoc design with withdrawal effects inferred from temporal variation rather than randomized discontinuation. Severe exacerbation analyses were underpowered, and the LAMA signal was most evident in a subgroup least affected by concomitant ICS.","practice_takeaway":"Expect a transient rise in COPD exacerbations in the first 3 months after stopping LAMA or ICS; reinforce adherence and monitor closely soon after withdrawal. The early ICS withdrawal risk for severe events appears independent of baseline blood eosinophil count."}},{"doi":"10.1111/jdv.70250","pmid":"41401055","title":"Rapid improvement of itch with nemolizumab in atopic dermatitis and prurigo nodularis phase 3 studies","journal_title":"Journal of the European Academy of Dermatology and Venereology","journal_issn":"0926-9959","published_at":"2025-12-16T00:00:00.000Z","url":"https://doi.org/10.1111/jdv.70250","source_score":276,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-16","doi":"10.1111/jdv.70250","days":"30","issn":"0926-9959","rank":"2","field":"Clinical Medicine","score":"276","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1111/jdv.70250","title":"Rapid improvement of itch with nemolizumab in atopic dermatitis and prurigo nodularis phase 3 studies.","journal":"Journal of the European Academy of Dermatology and Venereology : JEADV","methods":"","results":"Nemolizumab rapidly reduced itch in AD (ARCADIA 1 and 2), with a difference versus placebo in PP-NRS responders apparent by Day 2 (pooled data: 10.7% vs. 2.9%; 95% CI: 5.6-10.1; p < 0.0001) that steadily increased through Day 14. Nemolizumab also reduced itch rapidly in PN (OLYMPIA 1 and 2); a difference versus placebo occurred by Day 2 (pooled data: 17.2% vs. 3.7%; 95% CI: 6.8-16.7; p < 0.0001). Early improvement (Day 2) was also observed in sleep in nemolizumab-treated patients. In pooled analyses in AD, 9.9% (nemolizumab) versus 4.6% (placebo; 95% CI: 2.8-7.7; p = 0.0001) were SD-NRS responders and in PN, 13.4% versus 4.3% (95% CI: 4.0-13.0; p = 0.0013). Itch and sleep response data in individual studies were consistent with the pooled data.","abstract":"$36","keywords":["atopic dermatitis","eczematous disease","interleukin 31","itch","nemolizumab","onset of action","prurigo nodularis","pruritus","sleep disturbance"],"pubmed_id":"41401055","conclusions":"","publication_date":"2025-12-16T00:00:00"},"crossref":{"DOI":"10.1111/jdv.70250","URL":"https://doi.org/10.1111/jdv.70250","ISSN":["0926-9959","1468-3083"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.70250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Rapid improvement of itch with nemolizumab in atopic dermatitis and prurigo nodularis phase 3 studies"],"author":[{"given":"Sonja","family":"Ständer","sequence":"first","affiliation":[{"name":"Section Pruritus Medicine, Department of Dermatology and Center for Chronic Pruritus University Hospital Münster Münster Germany"}]},{"given":"Sarina B.","family":"Elmariah","sequence":"additional","affiliation":[{"name":"University of California San Francisco Center for Itch and Neurosensory Disorders San Francisco California USA"}]},{"given":"Shawn G.","family":"Kwatra","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Maryland School of Medicine Baltimore Maryland USA"}]},{"given":"Gil","family":"Yosipovitch","sequence":"additional","affiliation":[{"name":"Dr Philip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, Miami Itch Center University of Miami Miami Florida USA"}]},{"given":"Andrew E.","family":"Pink","sequence":"additional","affiliation":[{"name":"St John's Institute of Dermatology Guy's and St Thomas' NHS Foundation Trust and King's College London London UK"}]},{"given":"Soo Yeon","family":"Cheong","sequence":"additional","affiliation":[{"name":"Galderma Laboratories, LP Dallas Texas USA"}]},{"given":"Xiaoxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Galderma Laboratories, LP Dallas Texas USA"}]},{"given":"Zarif K.","family":"Jabbar‐Lopez","sequence":"additional","affiliation":[{"name":"Galderma Research and Development Zug Switzerland"}]},{"given":"Liliana","family":"Ulianov","sequence":"additional","affiliation":[{"name":"Galderma Research and Development Zug Switzerland"}]},{"given":"Christophe","family":"Piketty","sequence":"additional","affiliation":[{"name":"Galderma Laboratories, LP Dallas Texas USA"}]},{"given":"Jonathan I.","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Department of Dermatology The George Washington School of Medicine and Health Sciences Washington DC USA"}]}],"funder":[{"id":[{"id":"10.13039/501100009754","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100009754","name":"Galderma","doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2025,12,16]]},"member":"311","prefix":"10.1111","source":"Crossref","volume":null,"archive":["Portico"],"created":{"date-time":"2025-12-16T17:30:10Z","timestamp":1765906210000,"date-parts":[[2025,12,16]]},"indexed":{"date-time":"2025-12-16T17:34:29Z","timestamp":1765906469818,"date-parts":[[2025,12,16]]},"license":[{"URL":"http://creativecommons.org/licenses/by-nc/4.0/","start":{"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000,"date-parts":[[2025,12,16]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$37","language":"en","relation":{},"resource":{"primary":{"URL":"https://onlinelibrary.wiley.com/doi/10.1111/jdv.70250"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2025-09-01"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":2,"value":"2025-10-11"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":3,"value":"2025-12-16"}],"deposited":{"date-time":"2025-12-16T17:30:11Z","timestamp":1765906211000,"date-parts":[[2025,12,16]]},"issn-type":[{"type":"print","value":"0926-9959"},{"type":"electronic","value":"1468-3083"}],"published":{"date-parts":[[2025,12,16]]},"publisher":"Wiley","reference":[{"DOI":"10.1093/bjd/ljae052","key":"e_1_2_13_2_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.clindermatol.2025.03.009","key":"e_1_2_13_3_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(24)01203-0","key":"e_1_2_13_4_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(15)00149-X","key":"e_1_2_13_5_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.alit.2016.08.009","key":"e_1_2_13_6_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/jdv.16309","key":"e_1_2_13_7_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.anai.2018.07.006","key":"e_1_2_13_8_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.2340/00015555-3778","key":"e_1_2_13_9_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.2340/00015555-3726","key":"e_1_2_13_10_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/jdv.20148","key":"e_1_2_13_11_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1007/s13555-023-00999-9","key":"e_1_2_13_12_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/jdv.17870","key":"e_1_2_13_13_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/all.14791","key":"e_1_2_13_14_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3389/fmed.2021.638325","key":"e_1_2_13_15_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.molmed.2022.03.005","key":"e_1_2_13_16_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaci.2013.10.048","key":"e_1_2_13_17_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa2301333","key":"e_1_2_13_18_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/jdv.17218","key":"e_1_2_13_19_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1001/jamadermatol.2024.4796","key":"e_1_2_13_20_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/jdv.18377","key":"e_1_2_13_21_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/bjd.17744","key":"e_1_2_13_22_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1007/s13555-023-00962-8","key":"e_1_2_13_23_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/bjd.20783","key":"e_1_2_13_24_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/jid.2013.446","key":"e_1_2_13_25_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1001/jamadermatol.2016.5538","key":"e_1_2_13_26_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3389/fimmu.2019.01303","key":"e_1_2_13_27_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1007/s40257-022-00738-4","key":"e_1_2_13_28_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(21)00588-2","key":"e_1_2_13_29_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2020.02.060","key":"e_1_2_13_30_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41591-023-02320-9","key":"e_1_2_13_31_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaci.2022.01.028","key":"e_1_2_13_32_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"}],"short-title":[],"update-policy":"https://doi.org/10.1002/crossmark_policy","alternative-id":["10.1111/jdv.70250"],"article-number":"jdv.70250","content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"reference-count":31,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,12,16]]},"references-count":31,"short-container-title":["Acad Dermatol Venereol"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1111/jdv.70250","is_oa":true,"title":"Rapid improvement of itch with nemolizumab in atopic dermatitis and prurigo nodularis phase 3 studies","updated":"2025-12-17T23:50:37+00:00","published_date":"2025-12-16","best_oa_location":{"url":"https://doi.org/10.1111/jdv.70250","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.1111/jdv.70250"}}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-15T20:51:27.064Z","tags":[{"paper_doi":"10.1111/jdv.70250","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"condition","value":"Atopic Dermatitis","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"condition","value":"Prurigo Nodularis","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"generic","value":"nemolizumab","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"modality","value":"IL-31 Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"sample_size","value":"n=2288","value_numeric":2288},{"paper_doi":"10.1111/jdv.70250","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"warning","value":"Age group and sex distribution are not specified in the abstract.","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"warning","value":"Design classification is approximate: this is a post hoc pooled analysis of four randomized trials, not a standalone RCT.","value_numeric":null},{"paper_doi":"10.1111/jdv.70250","tag_type":"warning","value":"Responder outcomes are based on ≥4‑point improvements in PP‑NRS and SD‑NRS at early time points.","value_numeric":null}],"summaries":{"what_studied":"Post hoc pooled analysis of four phase 3 randomized trials (ARCADIA 1/2 in atopic dermatitis; OLYMPIA 1/2 in prurigo nodularis; N=1728 and N=560) evaluating nemolizumab versus placebo for early itch and sleep improvement over the first 14 days using daily PP-NRS and SD-NRS diaries.","key_result":"By Day 2, PP-NRS responder rates (≥4‑point improvement) were higher with nemolizumab vs placebo: 10.7% vs 2.9% in atopic dermatitis (95% CI 5.6–10.1; p<0.0001) and 17.2% vs 3.7% in prurigo nodularis (95% CI 6.8–16.7; p<0.0001); Day 2 SD-NRS responders were 9.9% vs 4.6% in atopic dermatitis (95% CI 2.8–7.7; p=0.0001) and 13.4% vs 4.3% in prurigo nodularis (95% CI 4.0–13.0; p=0.0013), with effects increasing through Day 14.","limitations":"Post hoc design pooling four trials; analyses focus on the first 14 days only and rely on patient-reported NRS outcomes.","practice_takeaway":"Nemolizumab produced clinically meaningful itch relief by 48 hours and improved sleep versus placebo in moderate-to-severe atopic dermatitis and prurigo nodularis, with benefits growing over two weeks."}},{"doi":"10.1001/jamainternmed.2025.6112","pmid":"41284285","title":"Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity","journal_title":"JAMA Internal Medicine","journal_issn":"2168-6106","published_at":"2025-11-24T00:00:00.000Z","url":"https://doi.org/10.1001/jamainternmed.2025.6112","source_score":334,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-11-27","doi":"10.1001/jamainternmed.2025.6112","days":"7","issn":"2168-6106","rank":"6","field":"Clinical Medicine","score":"334","category":"Medicine, General & Internal","categories":["Medicine, General & Internal"],"_categories":["Medicine, General & Internal"]},"pubmed":{"doi":"10.1001/jamainternmed.2025.6112","title":"Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial.","journal":"JAMA internal medicine","methods":"","results":"$38","abstract":"$39","keywords":[],"pubmed_id":"41284285","conclusions":"","publication_date":"2025-11-24T00:00:00"},"crossref":{"DOI":"10.1001/jamainternmed.2025.6112","URL":"https://doi.org/10.1001/jamainternmed.2025.6112","ISSN":["2168-6106"],"link":[{"URL":"https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/2841273/jamainternal_horn_2025_oi_250074_1762368708.42062.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity"],"author":[{"given":"Deborah B.","family":"Horn","sequence":"first","affiliation":[{"name":"University of Texas Center for Obesity Medicine and Metabolic Performance, Department of Surgery, McGovern Medical School, Houston"}]},{"given":"Bruno","family":"Linetzky","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana"}]},{"given":"Melanie J.","family":"Davies","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, University of Leicester, NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom"}]},{"given":"Luke J.","family":"Laffin","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundation, Cleveland, Ohio"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"TechData Service Company, King of Prussia, Pennsylvania"}]},{"given":"Madhumita A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana"}]},{"given":"Sarah","family":"Zimner-Rapuch","sequence":"additional","affiliation":[{"name":"Lilly France, Neuilly-sur-Seine, France"}]},{"given":"Eva","family":"Lau","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Lisbon, Portugal"}]},{"given":"Avigdor D.","family":"Arad","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana"}]},{"given":"Clare J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana"}]}],"issued":{"date-parts":[[2025,11,24]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":null,"created":{"date-time":"2025-11-24T16:31:18Z","timestamp":1764001878000,"date-parts":[[2025,11,24]]},"indexed":{"date-time":"2025-11-24T16:38:10Z","timestamp":1764002290200,"date-parts":[[2025,11,24]]},"subject":[],"abstract":"$3a","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2841273"}},"subtitle":["A Post Hoc Analysis of the SURMOUNT-4 Trial"],"deposited":{"date-time":"2025-11-24T16:31:21Z","timestamp":1764001881000,"date-parts":[[2025,11,24]]},"issn-type":[{"type":"print","value":"2168-6106"}],"published":{"date-parts":[[2025,11,24]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.1503/cmaj.191707","key":"ioi250074r1","year":"2020","issue":"31","author":"Wharton","volume":"192","first-page":"E875","unstructured":null,"article-title":"Obesity in adults: a clinical practice guideline.","journal-title":"CMAJ","doi-asserted-by":"publisher"},{"DOI":"10.4158/EP161365.GL","key":"ioi250074r2","year":"2016","issue":null,"author":"Garvey","volume":"22","first-page":"1","unstructured":null,"article-title":"American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity.","journal-title":"Endocr Pract","doi-asserted-by":"publisher"},{"DOI":"10.1210/jc.2014-3415","key":"ioi250074r3","year":"2015","issue":"2","author":"Apovian","volume":"100","first-page":"342","unstructured":null,"article-title":"Pharmacological management of obesity: an Endocrine Society clinical practice guideline.","journal-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher"},{"DOI":"10.1016/S2213-8587(24)00316-4","key":"ioi250074r4","year":"2025","issue":"3","author":"Rubino","volume":"13","first-page":"221","unstructured":null,"article-title":"Definition and diagnostic criteria of clinical obesity.","journal-title":"Lancet Diabetes Endocrinol","doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(00)03491-7","key":"ioi250074r5","year":"2000","issue":"9248","author":"James","volume":"356","first-page":"2119","unstructured":null,"article-title":"Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance.","journal-title":"Lancet","doi-asserted-by":"publisher"},{"DOI":"10.1001/jama.2021.3224","key":"ioi250074r6","year":"2021","issue":"14","author":"Rubino","volume":"325","first-page":"1414","unstructured":null,"article-title":"Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial.","journal-title":"JAMA","doi-asserted-by":"publisher"},{"DOI":"10.1001/jama.2023.24945","key":"ioi250074r7","year":"2024","issue":"1","author":"Aronne","volume":"331","first-page":"38","unstructured":null,"article-title":"Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial.","journal-title":"JAMA","doi-asserted-by":"publisher"},{"DOI":"10.1161/JAHA.118.010951","key":"ioi250074r10","year":"2019","issue":"20","author":"Berger","volume":"8","first-page":null,"unstructured":null,"article-title":"Change in cardiometabolic risk factors associated with magnitude of weight regain 3 years after a 1-year intensive lifestyle intervention in type 2 diabetes mellitus: the Look AHEAD trial.","journal-title":"J Am Heart Assoc","doi-asserted-by":"publisher"},{"DOI":"10.1111/dom.14725","key":"ioi250074r11","year":"2022","issue":"8","author":"Wilding","volume":"24","first-page":"1553","unstructured":null,"article-title":"Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.","journal-title":"Diabetes Obes Metab","doi-asserted-by":"publisher"},{"DOI":"10.3945/ajcn.110.004895","key":"ioi250074r12","year":"2011","issue":"3","author":"Beavers","volume":"94","first-page":"767","unstructured":null,"article-title":"Is lost lean mass from intentional weight loss recovered during weight regain in postmenopausal women?","journal-title":"Am J Clin Nutr","doi-asserted-by":"publisher"},{"DOI":"10.1093/ajcn/56.2.320","key":"ioi250074r13","year":"1992","issue":"2","author":"Dattilo","volume":"56","first-page":"320","unstructured":null,"article-title":"Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis.","journal-title":"Am J Clin Nutr","doi-asserted-by":"publisher"},{"DOI":"10.1186/s12933-023-01797-5","key":"ioi250074r14","year":"2023","issue":"1","author":"Lingvay","volume":"22","first-page":"66","unstructured":null,"article-title":"Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from SURPASS clinical program.","journal-title":"Cardiovasc Diabetol","doi-asserted-by":"publisher"},{"DOI":"10.1161/HYPERTENSIONAHA.123.22022","key":"ioi250074r15","year":"2024","issue":"4","author":"de Lemos","volume":"81","first-page":"e41","unstructured":null,"article-title":"Tirzepatide reduces 24-hour ambulatory blood pressure in adults with body mass index =27 kg/m2: SURMOUNT-1 ambulatory blood pressure monitoring substudy.","journal-title":"Hypertension","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.coph.2023.102355","key":"ioi250074r16","year":"2023","issue":null,"author":"Ribeiro-Silva","volume":"69","first-page":null,"unstructured":null,"article-title":"The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: a mini-review of the potential mechanisms.","journal-title":"Curr Opin Pharmacol","doi-asserted-by":"publisher"},{"DOI":"10.2337/cd22-0029","key":"ioi250074r17","year":"2023","issue":"2","author":"Kushner","volume":"41","first-page":"258","unstructured":null,"article-title":"Efficacy and safety of tirzepatide in adults with type 2 diabetes: a perspective for primary care providers.","journal-title":"Clin Diabetes","doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa2410819","key":"ioi250074r18","year":"2025","issue":"10","author":"Jastreboff","volume":"392","first-page":"958","unstructured":null,"article-title":"Tirzepatide for obesity treatment and diabetes prevention.","journal-title":"N Engl J Med","doi-asserted-by":"publisher"},{"DOI":"10.1210/jendso/bvad056","key":"ioi250074r19","year":"2023","issue":"5","author":"Lee","volume":"7","first-page":null,"unstructured":null,"article-title":"Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1).","journal-title":"J Endocr Soc","doi-asserted-by":"publisher"},{"DOI":"10.1210/clinem/dgae319","key":"ioi250074r20","year":"2024","issue":"12","author":"Mather","volume":"109","first-page":"3046","unstructured":null,"article-title":"Effects of tirzepatide vs semaglutide on ß-cell function, insulin sensitivity, and glucose control during a meal test.","journal-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher"},{"DOI":"10.2337/dc16-0509","key":"ioi250074r21","year":"2016","issue":"8","author":"Wing","volume":"39","first-page":"1345","unstructured":null,"article-title":"Association of weight loss maintenance and weight regain on 4-year changes in CVD risk factors: the Action for Health in Diabetes (Look AHEAD) clinical trial.","journal-title":"Diabetes Care","doi-asserted-by":"publisher"},{"DOI":"10.1111/cob.12203","key":"ioi250074r22","year":"2017","issue":"5","author":"Kolotkin","volume":"7","first-page":"273","unstructured":null,"article-title":"A systematic review of reviews: exploring the relationship between obesity, weight loss and health-related quality of life.","journal-title":"Clin Obes","doi-asserted-by":"publisher"},{"DOI":null,"key":"ioi250074r8","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Zepbound. Prescribing information. Eli Lilly and Company; 2024. Accessed October 21, 2024. https://pi.lilly.com/us/zepbound-uspi.pdf","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"ioi250074r9","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Mounjaro. Prescribing information. Eli Lilly and Company; 2023. Accessed October 21, 2024. https://pi.lilly.com/us/mounjaro-uspi.pdf","article-title":null,"journal-title":null,"doi-asserted-by":null}],"short-title":[],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Internal Medicine"],"reference-count":22,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,11,24]]},"references-count":22,"short-container-title":["JAMA Intern Med"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1001/jamainternmed.2025.6112","is_oa":false,"title":"Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity","updated":"2025-11-25T15:53:31+00:00","published_date":"2025-11-24","best_oa_location":null}},"created_at":"2025-12-08T12:24:58.509Z","updated_at":"2025-12-08T12:24:58.509Z","tags":[{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"generic","value":"tirzepatide","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"modality","value":"Dual GIP/GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"sample_size","value":"n=308","value_numeric":308},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"warning","value":"Design classified as a post hoc analysis of an RCT; causality and effect sizes may be influenced by subgrouping by weight regain.","value_numeric":null},{"paper_doi":"10.1001/jamainternmed.2025.6112","tag_type":"warning","value":"Generalizability is limited to participants who lost ≥10% on tirzepatide and were switched to placebo at week 36.","value_numeric":null}],"summaries":{"what_studied":"A post hoc analysis of SURMOUNT-4 evaluated adults with obesity who lost at least 10% weight after 36 weeks of tirzepatide and were then switched to placebo, assessing 52-week changes (week 36 to 88) in cardiometabolic measures by degree of weight regain (<25%, 25%–<50%, 50%–<75%, ≥75%).","key_result":"Among 308 participants, greater weight regain was linked to larger reversals in risk factors: waist circumference rose from 0.8 cm (<25% regain) to 14.7 cm (≥75%); systolic BP increased 6.8–10.4 mm Hg; non-HDL cholesterol changed −0.4% to +10.8%; HbA1c increased 0.14% to 0.35%; fasting insulin changed −4.0% to +46.2%. In the <25% regain group, week‑88 changes in waist, non‑HDL cholesterol, and fasting insulin were not significantly different vs week 36.","limitations":"Post hoc design limits causal inference. Analysis was restricted to participants who achieved ≥10% weight loss and were randomized to placebo at week 36, which may limit generalizability.","practice_takeaway":"When tirzepatide is withdrawn, most patients regain ≥25% of lost weight within a year and cardiometabolic gains wane in proportion to regain; maintaining weight loss attenuates this reversal. Continue obesity treatment to help preserve cardiometabolic improvements."}},{"doi":"10.1111/jocd.15947","pmid":"37616390","title":"Self‐perception of natural outcome, appearance, and emotional well‐being after OnabotulinumtoxinA treatment for upper facial lines: Post hoc analysis across age and gender","journal_title":"Journal of Cosmetic Dermatology","journal_issn":"1473-2130","published_at":"2023-08-24T00:00:00.000Z","url":"https://doi.org/10.1111/jocd.15947","source_score":253,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2023-09-08","doi":"10.1111/jocd.15947","days":"30","issn":"1473-2130","rank":"5","field":"Clinical Medicine","score":"253","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1111/jocd.15947","title":"Self-perception of natural outcome, appearance, and emotional well-being after OnabotulinumtoxinA treatment for upper facial lines: Post hoc analysis across age and gender.","journal":"Journal of cosmetic dermatology","methods":"","results":"At Day 30, 90.5% of all participants, 94.6% of millennials, and 85.7% of men were satisfied with receiving a natural look. Millennials had higher odds of being satisfied with natural outcomes at Day 30. This measure remained > 80% for all groups throughout the 12 months. Additionally, ≥80% were satisfied with the treatment effect, and >90% reported results met expectations. At Day 30, ≥50% reported positive impacts on self-perceived appearance and psychological well-being, but millennials had higher, and men had lower odds of reporting these improvements.","abstract":"$3b","keywords":["botulinum toxin","men","millennials","natural look","patient-reported outcomes"],"pubmed_id":"37616390","conclusions":"","publication_date":"2023-08-24T00:00:00"},"crossref":{"DOI":"10.1111/jocd.15947","URL":"https://doi.org/10.1111/jocd.15947","ISSN":["1473-2130","1473-2165"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jocd.15947","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"107-116","type":"journal-article","issue":"1","score":1,"title":["Self‐perception of natural outcome, appearance, and emotional well‐being after OnabotulinumtoxinA treatment for upper facial lines: Post hoc analysis across age and gender"],"author":[{"given":"Steven","family":"Dayan","sequence":"first","affiliation":[{"name":"Denova Research Chicago Illinois USA"}]},{"given":"Patricia","family":"Ogilvie","sequence":"additional","affiliation":[{"name":"Skin Concept Munich Germany"}]},{"given":"Charles","family":"Boyd","sequence":"additional","affiliation":[{"name":"BOYD Birmingham Michigan USA"}]},{"given":"Koenraad","family":"De Boulle","sequence":"additional","affiliation":[{"name":"Aalst Dermatology Clinic Aalst Belgium"}]},{"given":"Maurizio","family":"Cavallini","sequence":"additional","affiliation":[{"name":"Unit of Dermatology and Dermatosurgery, Centro Diagnostico Italiano Milan Italy"}]},{"given":"Julia K.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Allergan Aesthetics, an AbbVie Company Irvine California USA"}]},{"given":"Maria","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Allergan Aesthetics, an AbbVie Company Rome Italy"}]}],"funder":[{"id":[{"id":"10.13039/100006483","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100006483","name":"AbbVie","doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/100007819","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100007819","name":"Allergan","doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2023,8,24]]},"member":"311","prefix":"10.1111","source":"Crossref","volume":"23","archive":["Portico"],"created":{"date-time":"2023-08-24T18:08:10Z","timestamp":1692900490000,"date-parts":[[2023,8,24]]},"indexed":{"date-time":"2025-08-20T12:44:01Z","timestamp":1755693841745,"date-parts":[[2025,8,20]]},"license":[{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000,"date-parts":[[2023,8,24]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$3c","language":"en","relation":{},"resource":{"primary":{"URL":"https://onlinelibrary.wiley.com/doi/10.1111/jocd.15947"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2023-03-31"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":1,"value":"2023-07-22"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":2,"value":"2023-08-24"}],"deposited":{"date-time":"2024-02-09T01:37:22Z","timestamp":1707442642000,"date-parts":[[2024,2,9]]},"issn-type":[{"type":"print","value":"1473-2130"},{"type":"electronic","value":"1473-2165"}],"published":{"date-parts":[[2023,8,24]]},"publisher":"Wiley","reference":[{"DOI":null,"key":"e_1_2_12_2_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"2020 Plastic Surgery Statistics Report.American Society of Plastic Surgeons.2022.https://www.plasticsurgery.org/documents/News/Statistics/2020/plastic‐surgery‐statistics‐full‐report‐2020.pdf","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.36849/jdd.2022.6425","key":"e_1_2_12_3_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/asj/sjab015","key":"e_1_2_12_4_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000000876","key":"e_1_2_12_5_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/asj/sjab358","key":"e_1_2_12_6_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/jocd.12128","key":"e_1_2_12_7_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1080/17429590701523927","key":"e_1_2_12_8_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/01.prs.0000475758.63709.23","key":"e_1_2_12_9_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1001/jamadermatol.2018.2357","key":"e_1_2_12_10_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000001414","key":"e_1_2_12_11_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000001612","key":"e_1_2_12_12_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000002153","key":"e_1_2_12_13_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/jocd.12166","key":"e_1_2_12_14_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000000424","key":"e_1_2_12_15_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000002216","key":"e_1_2_12_16_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000002047","key":"e_1_2_12_17_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/gox.0000000000002669","key":"e_1_2_12_18_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1097/dss.0000000000000357","key":"e_1_2_12_19_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/asj/sjac157","key":"e_1_2_12_20_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/asj/sjab114","key":"e_1_2_12_21_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/asjof/ojab036","key":"e_1_2_12_22_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1007/s00266-015-0454-3","key":"e_1_2_12_23_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.36849/jdd.2020.4641","key":"e_1_2_12_24_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/asj/sjac253","key":"e_1_2_12_25_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/j.1524-4725.2005.31206","key":"e_1_2_12_26_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"}],"short-title":[],"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"update-policy":"http://dx.doi.org/10.1002/crossmark_policy","alternative-id":["10.1111/jocd.15947"],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Journal of Cosmetic Dermatology"],"published-print":{"date-parts":[[2024,1]]},"reference-count":25,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2023,8,24]]},"references-count":25,"short-container-title":["J of Cosmetic Dermatology"],"is-referenced-by-count":4},"unpaywall":{"doi":"10.1111/jocd.15947","is_oa":true,"title":"Self‐perception of natural outcome, appearance, and emotional well‐being after OnabotulinumtoxinA treatment for upper facial lines: Post hoc analysis across age and gender","updated":"2025-05-22T18:42:22+00:00","published_date":"2023-08-24","best_oa_location":{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jocd.15947","pmh_id":null,"url_for_pdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jocd.15947","url_for_landing_page":"https://doi.org/10.1111/jocd.15947"}}},"created_at":"2025-09-20T22:56:47.429Z","updated_at":"2025-09-21T04:08:53.191Z","tags":[{"paper_doi":"10.1111/jocd.15947","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"condition","value":"Upper Facial Lines","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"generic","value":"onabotulinumtoxinA","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"modality","value":"Botulinum Toxin Type A","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"sample_size","value":"n=458","value_numeric":458},{"paper_doi":"10.1111/jocd.15947","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"warning","value":"Design is a post hoc responder‑only analysis of two RCTs; findings may overestimate satisfaction.","value_numeric":null},{"paper_doi":"10.1111/jocd.15947","tag_type":"warning","value":"Male subgroup was small with notable attrition by the third treatment cycle.","value_numeric":null}],"summaries":{"what_studied":"Post hoc analysis of two 12‑month phase 3 randomized, placebo‑controlled trials evaluating patient‑reported outcomes after onabotulinumtoxinA for upper facial lines (20 U forehead, 20 U glabellar, ±24 U crow’s feet) in 458 neurotoxin‑naive adults who achieved ≥2‑grade forehead line improvement at Day 30; results stratified for millennials and men.","key_result":"At Day 30, 90.5% overall (94.6% millennials; 85.7% men) were satisfied with a natural look, with rates >80% across 12 months; at Day 60, 89.8% overall (95.7% millennials; 83.3% men) were satisfied with treatment effect, and >90% reported results met expectations. Millennials had higher odds of satisfaction (natural look OR 3.30, 95% CI 1.30–8.41; effect OR 2.22, 1.14–4.33), men had lower odds of psychological benefit (Impact Domain OR 0.43, 0.23–0.80), and repeat treatments increased odds of psychological benefit (OR 1.41 and 1.57 vs first).","limitations":"Responder‑only, post hoc analysis (included participants with ≥2‑grade forehead improvement) without an active comparator for PROs. Small male subgroup (n=43) with attrition by cycle 3, and a predominantly White, female sample limits generalizability.","practice_takeaway":"Among toxin‑naive adults who achieve a ≥2‑grade forehead line response on on‑label onabotulinumtoxinA dosing, most report natural‑looking results and high satisfaction for up to 12 months. Counsel that men may report less psychological benefit and that perceived appearance/emotional benefits may improve with repeat treatments."}}],"initialOffset":9,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"study_design","value":"Post Hoc Analysis"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Study Designs","href":"/hub/tag/study_design"},{"name":"Post Hoc Analysis"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"study_design","hub_tag_value":"Post Hoc Analysis"}}}]]

Papers