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:T87a,The German national psoriasis registry PsoBest collects long-term data on the effectiveness, safety, and tolerability of systemic treatments for psoriatic disease. Here, we describe patient characteristics and the safety and effectiveness of apremilast for the treatment of psoriatic disease in Germany based on data from PsoBest. This was a descriptive analysis of observational data collected from PsoBest using cross-sectional (baseline characteristics) and longitudinal (outcomes, safety) designs. PsoBest recruits patients with moderate to severe plaque psoriasis or psoriatic arthritis who initiate a new systemic psoriasis treatment. Adverse events (AEs) and sociodemographic descriptors were reported for patients exposed to apremilast during the study period (safety cohort). Clinical and patient-reported outcomes were collected 3, 6, and 12 months after the initiation of apremilast monotherapy (outcomes cohort). From January 15, 2015 to June 30, 2020, 595 registry patients were exposed to apremilast; 417 were treated with apremilast monotherapy. Patients taking apremilast had a higher mean age and higher proportions of comorbidities such as cardiovascular or metabolic disease compared with those taking other nonbiologic systemic or biologic drugs. The most common nonserious AEs were drug ineffectiveness (14.1%), diarrhea (9.4%), nausea (7.1%), and headache (6.1%). The highest incidence rates of nonserious and serious AEs of special interest were for infections and infestations per system organ class (8.03/100 patient-years) and malignant or unspecified tumors (2.50/100 patient-years), respectively. Improvements in Dermatology Life Quality Index, patient-defined treatment benefits (Patient Benefit Index), body surface area, and Psoriasis Area and Severity Index were observed after 3, 6, and 12 months of apremilast treatment. Patients in routine care treated with apremilast in the German PsoBest registry experienced treatment benefits and improved skin, psoriasis severity, and quality of life. Safety was consistent with the established safety profile. Apremilast is safe and effective for treating moderate to severe psoriatic disease.31:T4eb,Matthias Augustin: Consultant for, paid speaker for, and/or recipient of institutional research grants from AbbVie, Almirall, Amgen, Bayer Healthcare, Beiersdorf, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Centocor, Lilly, Fresenius, Galderma, GlaxoSmithKline, Hexal, Janssen, Klinge, LEO Pharma, MC2, Medac, Merck, MSD, Novartis, Pfizer, Sandoz, Sun Pharma, UCB, and Viatris. Stephan J. Rustenbach: No conflicts of interest to declare. Ralph von Kiedrowski: Consultant and/or paid speaker for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion HC, Fresenius Kabi, Galderma, Hexal, Lilly, Janssen, LEO Pharma, MoonLake, Novartis, Pfizer, Sanofi-Aventis, and UCB. Hamid Amouzadeh: Employment and stock ownership in Amgen. Kathy Tran: Employment and stock ownership in Amgen. Myriam Cordey: Employment and stock ownership in Amgen. Ulrich Mrowietz: Advisor for, received speakers’ honoraria and grants from, and participated in clinical trials for AbbVie, Aditxt, Almirall, Amgen, Aristea, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dr. Reddy’s, Lilly, Foamix, Formycon, Immunic, Janssen, LEO Pharma, Medac, MetrioPharm, Novartis, Phi-Stone, Pierre Fabre, Sanofi-Aventis, and UCB.32:T461,Among 82 399 individuals identified with PsA, 542 individuals (median [IQR] age, 52.5 [44.0-59.0] years; 341 female individuals [62.9%]) were receiving combination targeted therapy for 3 consecutive months and 200 (median [IQR] age, 55.0 [45.0-61.0] years; 114 female individuals [57.0%]) were receiving combination therapy for 6 consecutive months. The 2 most common combinations used were a tumor necrosis factor inhibitor with apremilast (34%-37%) and an interleukin 17 inhibitor with apremilast (27%-29%). The serious infection incidence rate among patients receiving combination targeted therapy ranged from 7.38 to 15.00 events per 1000 patients; the opportunistic infection incidence rate ranged from 0 to 1.85 events per 1000 patients. Patients receiving combination targeted therapy did not have a significantly increased risk of serious infection (propensity score-matched 3-month and 6-month RRs, 0.53 [95% CI, 0.17-1.63] and 1.50 [95% CI, 0.34-6.65], respectively) or opportunistic infection (adjusted 3-month and 6-month RRs, 1.00 [95% CI, 0.09-11.02] and not applicable, respectively) across all analyses.33:Tb5e,Achieving good disease control in psoriatic arthritis (PsA) remains a major challenge. Combining multiple systemic immunomodulatory therapies has been shown to be beneficial in other immune-mediated diseases with reasonable safety profiles, but data on the current use and safety of combination targeted therapy among individuals with PsA are limited. To evaluate the use and safety of combination targeted therapies among adults with PsA. Data from the IBM MarketScan Commercial Claims Database from January 2015 to December 2024 were used to describe use patterns and perform safety analyses. Data were analyzed from April 2024 to June 2025. A validated claims algorithm was used to identify adults with PsA, who were separated into a standard therapy control cohort that was matched 2:1 with the combination targeted therapy cohort. Descriptive analysis of the use of combination targeted therapies. The safety analysis included a comparison of frequencies of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for serious or opportunistic infections requiring an inpatient level of care. Relative risks (RRs) were calculated before and after propensity score matching. Among 82 399 individuals identified with PsA, 542 individuals (median [IQR] age, 52.5 [44.0-59.0] years; 341 female individuals [62.9%]) were receiving combination targeted therapy for 3 consecutive months and 200 (median [IQR] age, 55.0 [45.0-61.0] years; 114 female individuals [57.0%]) were receiving combination therapy for 6 consecutive months. The 2 most common combinations used were a tumor necrosis factor inhibitor with apremilast (34%-37%) and an interleukin 17 inhibitor with apremilast (27%-29%). The serious infection incidence rate among patients receiving combination targeted therapy ranged from 7.38 to 15.00 events per 1000 patients; the opportunistic infection incidence rate ranged from 0 to 1.85 events per 1000 patients. Patients receiving combination targeted therapy did not have a significantly increased risk of serious infection (propensity score-matched 3-month and 6-month RRs, 0.53 [95% CI, 0.17-1.63] and 1.50 [95% CI, 0.34-6.65], respectively) or opportunistic infection (adjusted 3-month and 6-month RRs, 1.00 [95% CI, 0.09-11.02] and not applicable, respectively) across all analyses. The results of this cohort study suggest that among commercially insured adults with PsA, around 1% of individuals were receiving combination targeted therapy. The most common combinations used different biologics with apremilast. This study found no significant difference between the incidence of serious bacterial and opportunistic infections requiring hospitalization compared with standard therapy, suggesting that combination targeted therapy may not be associated with significantly increased infection risk, but further larger studies are needed.34:Tffb, Importance Achieving good disease control in psoriatic arthritis (PsA) remains a major challenge. Combining multiple systemic immunomodulatory therapies has been shown to be beneficial in other immune-mediated diseases with reasonable safety profiles, but data on the current use and safety of combination targeted therapy among individuals with PsA are limited. Objective To evaluate the use and safety of combination targeted therapies among adults with PsA. Design, Setting, and Participants Data from the IBM MarketScan Commercial Claims Database from January 2015 to December 2024 were used to describe use patterns and perform safety analyses. Data were analyzed from April 2024 to June 2025. A validated claims algorithm was used to identify adults with PsA, who were separated into a standard therapy control cohort that was matched 2:1 with the combination targeted therapy cohort. Main Outcomes and Measures Descriptive analysis of the use of combination targeted therapies. The safety analysis included a comparison of frequencies of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for serious or opportunistic infections requiring an inpatient level of care. Relative risks (RRs) were calculated before and after propensity score matching. Results Among 82 399 individuals identified with PsA, 542 individuals (median [IQR] age, 52.5 [44.0-59.0] years; 341 female individuals [62.9%]) were receiving combination targeted therapy for 3 consecutive months and 200 (median [IQR] age, 55.0 [45.0-61.0] years; 114 female individuals [57.0%]) were receiving combination therapy for 6 consecutive months. The 2 most common combinations used were a tumor necrosis factor inhibitor with apremilast (34%-37%) and an interleukin 17 inhibitor with apremilast (27%-29%). The serious infection incidence rate among patients receiving combination targeted therapy ranged from 7.38 to 15.00 events per 1000 patients; the opportunistic infection incidence rate ranged from 0 to 1.85 events per 1000 patients. Patients receiving combination targeted therapy did not have a significantly increased risk of serious infection (propensity score–matched 3-month and 6-month RRs, 0.53 [95% CI, 0.17-1.63] and 1.50 [95% CI, 0.34-6.65], respectively) or opportunistic infection (adjusted 3-month and 6-month RRs, 1.00 [95% CI, 0.09-11.02] and not applicable, respectively) across all analyses. Conclusions and Relevance The results of this cohort study suggest that among commercially insured adults with PsA, around 1% of individuals were receiving combination targeted therapy. The most common combinations used different biologics with apremilast. This study found no significant difference between the incidence of serious bacterial and opportunistic infections requiring hospitalization compared with standard therapy, suggesting that combination targeted therapy may not be associated with significantly increased infection risk, but further larger studies are needed. 35:T725,Efficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel-group, double-blind trial (INTEGUMENT-PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2-5 years with AD. Patients aged 2-5 years with mild-to-moderate AD were treated with once-daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2-grade improvement from baseline) at Week 4. Other endpoints included ≥ 75% improvement in Eczema Area and Severity Index (EASI-75) and Worst Itch-Numeric Rating Score (WI-NRS) Success (≥ 4-point improvement in patients with baseline ≥ 4). Safety and tolerability were also assessed. Among 437 and 215 patients treated with roflumilast and vehicle, respectively, significantly greater proportions of the roflumilast group achieved Week-4 vIGA-AD Success (25.4% vs. 10.7%; p < 0.0001), EASI-75 (39.4% vs. 20.6%; p < 0.0001), and WI-NRS Success (35.3% vs. 18.0%; nominal p = 0.0002). Improvement in pruritus was observed within 24 h after the first application (nominal p = 0.0014). Treatment-emergent adverse event (TEAE) rates were low in both groups, and 98.9% were mild or moderate. At all timepoints, stinging/burning that caused definite discomfort was reported by ≤ 0.7% of caregivers of patients in the roflumilast group. In this Phase 3 trial, once-daily roflumilast cream 0.05% improved AD signs/symptoms in patients aged 2-5 years, with early pruritus improvement, low AE rates, and local tolerability comparable with vehicle. ClinicalTrials.gov: NCT04845620.36:T9b5,ABSTRACTBackground/ObjectivesEfficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel‐group, double‐blind trial (INTEGUMENT‐PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2–5 years with AD.MethodsPatients aged 2–5 years with mild‐to‐moderate AD were treated with once‐daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA‐AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2‐grade improvement from baseline) at Week 4. Other endpoints included ≥ 75% improvement in Eczema Area and Severity Index (EASI‐75) and Worst Itch‐Numeric Rating Score (WI‐NRS) Success (≥ 4‐point improvement in patients with baseline ≥ 4). Safety and tolerability were also assessed.ResultsAmong 437 and 215 patients treated with roflumilast and vehicle, respectively, significantly greater proportions of the roflumilast group achieved Week‐4 vIGA‐AD Success (25.4% vs. 10.7%; p < 0.0001), EASI‐75 (39.4% vs. 20.6%; p < 0.0001), and WI‐NRS Success (35.3% vs. 18.0%; nominal p = 0.0002). Improvement in pruritus was observed within 24 h after the first application (nominal p = 0.0014). Treatment‐emergent adverse event (TEAE) rates were low in both groups, and 98.9% were mild or moderate. At all timepoints, stinging/burning that caused definite discomfort was reported by ≤ 0.7% of caregivers of patients in the roflumilast group.ConclusionsIn this Phase 3 trial, once‐daily roflumilast cream 0.05% improved AD signs/symptoms in patients aged 2–5 years, with early pruritus improvement, low AE rates, and local tolerability comparable with vehicle. Trial Registration: ClinicalTrials.gov: NCT0484562037:T44d,Overall, 104 patients were randomized (mean [SD] age, 43.0 [15.4] years; 55 [52.9%] women; 4 [3.8%] Asian, 13 [12.5%] Black, and 87 [83.7%] White), including 70 with AD (41 women [58.6%]; mean [SD] ages, 41.4 [16.6] years in the PF-07038124 group and 36.1 [13.9] years in the vehicle group) and 34 with plaque psoriasis (20 men [58.8%]; mean [SD] ages, 51.8 [12.3] years in the PF-07038124 group and 51.2 [10.8] years in the vehicle group). Baseline characteristics were generally balanced. At week 6, the PF-07038124 groups showed significantly greater improvements compared with vehicle groups in EASI (least-squares mean CFB, -74.9% vs -35.5%; difference, -39.4% [90% CI, -58.8% to -20.1%]; P < .001) and PASI scores (CFB, -4.8 vs 0.1; difference, -4.9 [90% CI, -7.0 to -2.8]; P < .001). The number of patients with treatment-emergent adverse events was comparable between treatment groups in patients with AD (PF-07038124, 9 [25.0%]; vehicle, 9 [26.5%]) and plaque psoriasis (PF-07038124, 3 [17.6%]; vehicle, 6 [35.3%]). There were no application site reactions with PF-07038124 treatment.38:T958,Atopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions. To assess the efficacy and safety of the topical phosphodiesterase 4 inhibitor PF-07038124 in patients with AD and plaque psoriasis. This phase 2a, randomized, double-blind clinical trial was conducted from December 21, 2020, to August 18, 2021, at 34 sites across 4 countries. Eligible patients (aged 18-70 years) had mild to moderate AD (covering 5%-20% body surface area) or plaque psoriasis (covering 5%-15% body surface area). Data were analyzed until December 15, 2021. Patients were randomized (1:1) to PF-07038124, 0.01%, topical ointment or vehicle once daily for 6 weeks. The primary end point was the percent change from baseline (CFB) in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures included treatment-emergent adverse events, including application site reactions. Overall, 104 patients were randomized (mean [SD] age, 43.0 [15.4] years; 55 [52.9%] women; 4 [3.8%] Asian, 13 [12.5%] Black, and 87 [83.7%] White), including 70 with AD (41 women [58.6%]; mean [SD] ages, 41.4 [16.6] years in the PF-07038124 group and 36.1 [13.9] years in the vehicle group) and 34 with plaque psoriasis (20 men [58.8%]; mean [SD] ages, 51.8 [12.3] years in the PF-07038124 group and 51.2 [10.8] years in the vehicle group). Baseline characteristics were generally balanced. At week 6, the PF-07038124 groups showed significantly greater improvements compared with vehicle groups in EASI (least-squares mean CFB, -74.9% vs -35.5%; difference, -39.4% [90% CI, -58.8% to -20.1%]; P < .001) and PASI scores (CFB, -4.8 vs 0.1; difference, -4.9 [90% CI, -7.0 to -2.8]; P < .001). The number of patients with treatment-emergent adverse events was comparable between treatment groups in patients with AD (PF-07038124, 9 [25.0%]; vehicle, 9 [26.5%]) and plaque psoriasis (PF-07038124, 3 [17.6%]; vehicle, 6 [35.3%]). There were no application site reactions with PF-07038124 treatment. Topical PF-07038124 was well tolerated and demonstrated superior efficacy compared with vehicle in patients with mild to moderate AD and plaque psoriasis. ClinicalTrials.gov Identifier: NCT04664153.39:Tccc,ImportanceAtopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions.ObjectiveTo assess the efficacy and safety of the topical phosphodiesterase 4 inhibitor PF-07038124 in patients with AD and plaque psoriasis.Design, Setting, and ParticipantsThis phase 2a, randomized, double-blind clinical trial was conducted from December 21, 2020, to August 18, 2021, at 34 sites across 4 countries. Eligible patients (aged 18-70 years) had mild to moderate AD (covering 5%-20% body surface area) or plaque psoriasis (covering 5%-15% body surface area). Data were analyzed until December 15, 2021.InterventionsPatients were randomized (1:1) to PF-07038124, 0.01%, topical ointment or vehicle once daily for 6 weeks.Main Outcomes and MeasuresThe primary end point was the percent change from baseline (CFB) in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures included treatment-emergent adverse events, including application site reactions.ResultsOverall, 104 patients were randomized (mean [SD] age, 43.0 [15.4] years; 55 [52.9%] women; 4 [3.8%] Asian, 13 [12.5%] Black, and 87 [83.7%] White), including 70 with AD (41 women [58.6%]; mean [SD] ages, 41.4 [16.6] years in the PF-07038124 group and 36.1 [13.9] years in the vehicle group) and 34 with plaque psoriasis (20 men [58.8%]; mean [SD] ages, 51.8 [12.3] years in the PF-07038124 group and 51.2 [10.8] years in the vehicle group). Baseline characteristics were generally balanced. At week 6, the PF-07038124 groups showed significantly greater improvements compared with vehicle groups in EASI (least-squares mean CFB, −74.9% vs −35.5%; difference, −39.4% [90% CI, −58.8% to −20.1%]; P &lt; .001) and PASI scores (CFB, −4.8 vs 0.1; difference, −4.9 [90% CI, −7.0 to −2.8]; P &lt; .001). The number of patients with treatment-emergent adverse events was comparable between treatment groups in patients with AD (PF-07038124, 9 [25.0%]; vehicle, 9 [26.5%]) and plaque psoriasis (PF-07038124, 3 [17.6%]; vehicle, 6 [35.3%]). There were no application site reactions with PF-07038124 treatment.Conclusions and RelevanceTopical PF-07038124 was well tolerated and demonstrated superior efficacy compared with vehicle in patients with mild to moderate AD and plaque psoriasis.Trial RegistrationClinicalTrials.gov Identifier: NCT046641533a:T778,There remains an unmet need for oral medications that are safe and efficacious for long-term management of chronic inflammatory skin diseases (CISD). Inhibition of phosphodiesterase 4 (PDE4) can modulate a broad range of pro-inflammatory cytokines that play a major role in CISD pathogenesis. Orismilast is a second generation PDE4 inhibitor in clinical development for CISD treatment. The objective of this study was to examine the PDE4 enzymatic activity and anti-inflammatory effects of orismilast in vitro, ex vivo, and in vivo. The PDE1-11 enzymatic activity of orismilast was tested in vitro using a single concentration of 308 nM orismilast. The PDE4 selectivity and inhibitory potency was further examined in a radiometric assay. Orismilast was tested on human whole blood and human peripheral blood mononuclear cells (PBMC) to determine effects on its cytokine secretion and inhibition profile ex vivo. Orismilast was orally administered in a murine model of chronic oxazolone-induced ear skin inflammation. Ear thickness, a marker of inflammation, and inflammatory cytokines were analysed. Orismilast selectively inhibited PDE4 and demonstrated potent inhibition of PDE4B and PDE4D subtype splice variants in vitro. Orismilast inhibited whole blood and PBMC production of tumour necrosis factor α (TNFα), and the secretion of T-helper (Th)1 (TNFα and IFNγ), Th17 (IL-22 and IL-23), and Th2 (IL-4, IL-5, and IL-13) related cytokines in PBMC. In vivo, 10 and 30 mg/kg doses of orismilast significantly reduced ear thickness and inflammation markers (p < 0.0001, respectively). Orismilast displayed selective and potent PDE4 inhibition and broad-spectrum anti-inflammatory activity in several pre-clinical models. The results of the study support clinical development of oral orismilast as a novel treatment option for CISD including psoriasis, atopic dermatitis, and hidradenitis suppurativa.3b:T987,AbstractBackgroundThere remains an unmet need for oral medications that are safe and efficacious for long‐term management of chronic inflammatory skin diseases (CISD). Inhibition of phosphodiesterase 4 (PDE4) can modulate a broad range of pro‐inflammatory cytokines that play a major role in CISD pathogenesis. Orismilast is a second generation PDE4 inhibitor in clinical development for CISD treatment.ObjectivesThe objective of this study was to examine the PDE4 enzymatic activity and anti‐inflammatory effects of orismilast in vitro, ex vivo, and in vivo.MethodsThe PDE1‐11 enzymatic activity of orismilast was tested in vitro using a single concentration of 308 nM orismilast. The PDE4 selectivity and inhibitory potency was further examined in a radiometric assay. Orismilast was tested on human whole blood and human peripheral blood mononuclear cells (PBMC) to determine effects on its cytokine secretion and inhibition profile ex vivo. Orismilast was orally administered in a murine model of chronic oxazolone‐induced ear skin inflammation. Ear thickness, a marker of inflammation, and inflammatory cytokines were analysed.ResultsOrismilast selectively inhibited PDE4 and demonstrated potent inhibition of PDE4B and PDE4D subtype splice variants in vitro. Orismilast inhibited whole blood and PBMC production of tumour necrosis factor α (TNFα), and the secretion of T‐helper (Th)1 (TNFα and IFNγ), Th17 (IL‐22 and IL‐23), and Th2 (IL‐4, IL‐5, and IL‐13) related cytokines in PBMC. In vivo, 10 and 30 mg/kg doses of orismilast significantly reduced ear thickness and inflammation markers (p < 0.0001, respectively).ConclusionOrismilast displayed selective and potent PDE4 inhibition and broad‐spectrum anti‐inflammatory activity in several pre‐clinical models. The results of the study support clinical development of oral orismilast as a novel treatment option for CISD including psoriasis, atopic dermatitis, and hidradenitis suppurativa.3c:T7c8,Orismilast is a high-potency phosphodiesterase 4 (PDE4) inhibitor with enhanced selectivity for the PDE4B and PDE4D subtypes. The objective of this phase 2a trial was to examine the efficacy and safety of orismilast for psoriasis using a first-generation immediate-release (IR) formulation. The objective of the subsequent phase 1 trial was to test new formulations designed to minimize the gastrointestinal (GI)-related adverse events (AEs) observed with the first-generation IR formulation. We examined the following: (1) pharmacokinetic (PK) properties of orismilast modified release (MR) and IR, (2) food effects on PK properties of orismilast MR or IR, (3) safety of orismilast MR compared to placebo. In a phase 2a prospective, randomized, double-blind, placebo-controlled trial, patients with moderate-to-severe psoriasis were randomized to receive 30 mg oral orismilast IR or placebo over 16 weeks. The single-site phase 1 trial consisted of three parts: (1) participants received a single 30 mg dose of orismilast MR and IR (open-label), (2) participants received 30 mg orismilast MR or IR under either fasting condition, following a high-fat meal or low-fat meal (open-label) and (3) participants received up to 60 mg orismilast MR twice-daily or a placebo for 17 days (double-blind). In the phase 2a trial, treatment with orismilast IR significantly improved the mean Psoriasis Area Severity Index score at week 16 compared to placebo. The phase 1 trial revealed comparable PK properties of the orismilast MR and IR formulations, with participants in the orismilast MR group experiencing fewer GI-related AEs than those receiving orismilast IR (16.7% vs. 33.3%). Orismilast IR displayed higher efficacy compared to placebo in patients with moderate-to-severe psoriasis at week 16. Orismilast MR had similar PK properties and fewer GI disorders compared to the IR formulation in healthy participants. Future development of orismilast will be based on the MR formulation.3d:T972,AbstractBackgroundOrismilast is a high‐potency phosphodiesterase 4 (PDE4) inhibitor with enhanced selectivity for the PDE4B and PDE4D subtypes.ObjectivesThe objective of this phase 2a trial was to examine the efficacy and safety of orismilast for psoriasis using a first‐generation immediate‐release (IR) formulation. The objective of the subsequent phase 1 trial was to test new formulations designed to minimize the gastrointestinal (GI)‐related adverse events (AEs) observed with the first‐generation IR formulation. We examined the following: (1) pharmacokinetic (PK) properties of orismilast modified release (MR) and IR, (2) food effects on PK properties of orismilast MR or IR, (3) safety of orismilast MR compared to placebo.MethodsIn a phase 2a prospective, randomized, double‐blind, placebo‐controlled trial, patients with moderate‐to‐severe psoriasis were randomized to receive 30 mg oral orismilast IR or placebo over 16 weeks. The single‐site phase 1 trial consisted of three parts: (1) participants received a single 30 mg dose of orismilast MR and IR (open‐label), (2) participants received 30 mg orismilast MR or IR under either fasting condition, following a high‐fat meal or low‐fat meal (open‐label) and (3) participants received up to 60 mg orismilast MR twice‐daily or a placebo for 17 days (double‐blind).ResultsIn the phase 2a trial, treatment with orismilast IR significantly improved the mean Psoriasis Area Severity Index score at week 16 compared to placebo. The phase 1 trial revealed comparable PK properties of the orismilast MR and IR formulations, with participants in the orismilast MR group experiencing fewer GI‐related AEs than those receiving orismilast IR (16.7% vs. 33.3%).ConclusionOrismilast IR displayed higher efficacy compared to placebo in patients with moderate‐to‐severe psoriasis at week 16. Orismilast MR had similar PK properties and fewer GI disorders compared to the IR formulation in healthy participants. Future development of orismilast will be based on the MR formulation.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"PDE4 Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on PDE4 Inhibitor (modality). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/modality/PDE4%20Inhibitor\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Modalities\",\"item\":\"https://www.reachrx.ai/hub/tag/modality\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"PDE4 Inhibitor\",\"item\":\"https://www.reachrx.ai/hub/tag/modality/PDE4%20Inhibitor\"}]}}"}}]],["$","$L2f",null,{"title":"PDE4 Inhibitor: Research & Clinical Takeaways","description":"Review evidence by treatment modality: PDE4 Inhibitor — concise summaries and practical next steps.","papers":[{"doi":"10.3899/jrheum.2025-1171","pmid":"42542376","title":"Who Achieves Minimal and Very Low Disease Activity in Psoriatic Arthritis? An Analysis of the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry","journal_title":"The Journal of Rheumatology","journal_issn":"0315-162X","published_at":"2026-08-01T00:00:00.000Z","url":"https://doi.org/10.3899/jrheum.2025-1171","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-11T13:26:24.973Z","updated_at":"2026-08-11T13:26:24.973Z","tags":[{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"condition","value":"Psoriatic Arthritis","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"modality","value":"Biologic DMARD","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"modality","value":"IL-17 Inhibitor","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"modality","value":"IL-23 Inhibitor","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"modality","value":"Targeted Synthetic DMARD","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"modality","value":"TNF Inhibitor","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"sample_size","value":"n=2491","value_numeric":2491},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"study_design","value":"Prospective Observational Registry Study","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"warning","value":"Analyses were conducted at the b/tsDMARD initiation level, not patient level, so some patients contributed multiple observations; standard errors may be under- or overestimated.","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"warning","value":"Study was funded by UCB; two authors are UCB employees, which may introduce publication bias.","value_numeric":null},{"paper_doi":"10.3899/jrheum.2025-1171","tag_type":"warning","value":"The two cohorts (MDA: n=2,093; VLDA: n=2,491) are non-mutually exclusive and overlap; the larger VLDA cohort includes patients who were in MDA but not VLDA at baseline. The sample_size tag reflects the larger VLDA cohort.","value_numeric":null}],"summaries":{"what_studied":"This real-world registry study (CorEvitas PsA/SpA Registry, March 2013–September 2023) examined rates of minimal disease activity (MDA) and very low disease activity (VLDA) achievement in adults with PsA starting a b/tsDMARD, assessed at a follow-up visit ~6 months post-initiation (n=2,093 for MDA cohort; n=2,491 for VLDA cohort).","key_result":"Only 17.68% (370/2,093) achieved MDA and 7.51% (187/2,491) achieved VLDA at ~6 months. Pain was the most commonly unmet criterion: 95.41% of MDA non-achievers and 87.02% of VLDA non-achievers failed this threshold. Female sex, higher baseline fatigue/pain, and prior b/tsDMARD use were linked to lower MDA/VLDA likelihood; b/tsDMARD monotherapy (RR 1.36 [95% CI 1.07–1.73]) and higher EQ-5D-3L scores were linked to higher MDA likelihood. Notably, 23.10% of MDA non-achievers and 10.24% of VLDA non-achievers missed the target by just 1 criterion.","limitations":"- Registry-based design introduces selection bias and confounding by indication (e.g., sicker patients less likely to receive b/tsDMARDs).\n- Patients who discontinued their b/tsDMARD before follow-up were classified as non-achievers, potentially underestimating true MDA/VLDA rates.\n- Analyses at the b/tsDMARD initiation level (not patient level) may introduce within-patient correlation, affecting precision of confidence intervals.","practice_takeaway":"Most PsA patients on b/tsDMARDs do not reach MDA or VLDA at 6 months, with pain and patient-reported function as the biggest barriers—clinicians should address residual pain and PROs explicitly, not just joint counts. Nearly a quarter of MDA non-achievers missed the target by just one criterion, signaling that targeted pain management could meaningfully improve treat-to-target outcomes."}},{"doi":"10.1093/bjd/ljag174","pmid":"42082393","title":"Serious infection risk with systemic treatments for psoriasis: A cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)","journal_title":"British Journal of Dermatology","journal_issn":"0007-0963","published_at":"2026-05-05T00:00:00.000Z","url":"https://doi.org/10.1093/bjd/ljag174","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-09T13:22:33.628Z","updated_at":"2026-05-09T13:22:33.628Z","tags":[{"paper_doi":"10.1093/bjd/ljag174","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"brand","value":"Cosentyx","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"brand","value":"Enbrel","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"brand","value":"Humira","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"brand","value":"Otezla","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"brand","value":"Siliq","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"brand","value":"Skyrizi","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"condition","value":"Psoriasis","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"condition","value":"Serious Infection","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"generic","value":"adalimumab","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"generic","value":"apremilast","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"generic","value":"brodalumab","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"generic","value":"etanercept","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"generic","value":"risankizumab","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"generic","value":"secukinumab","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"modality","value":"IL-17 Inhibitor","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"modality","value":"IL-23 Inhibitor","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"modality","value":"TNF Inhibitor","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"sample_size","value":"n=18976","value_numeric":18976},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"warning","value":"Study design is labeled as a registry cohort (observational); the level of evidence reflects this, not a randomized trial.","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"warning","value":"The elevated serious infection signals for apremilast and secukinumab vs. adalimumab were not consistent in sensitivity analyses — these should not be interpreted as definitive safety differences.","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag174","tag_type":"warning","value":"Treatment episodes (n=46,770) far exceed patient count (n=18,976), meaning many patients switched treatments; channeling bias by disease severity or comorbidity cannot be fully excluded.","value_numeric":null}],"summaries":{"what_studied":"This large UK registry cohort (BADBIR) examined serious infection risk across systemic psoriasis treatments — including biologics (adalimumab, secukinumab, risankizumab, brodalumab, etanercept) and non-biologics (apremilast, standard treatments) — in 18,976 adult patients over 46,770 treatment episodes, using inverse probability weighting and both time-to-first-event and recurrent-event analyses.","key_result":"Overall serious infection incidence was 27.67 per 1,000 person-years; recurrent infection rate in those with prior infection was 78.70 per 1,000 person-years. The more robust recurrent-event (PWP) model showed risankizumab had lower serious infection risk vs. brodalumab (HR 0.74), etanercept (HR 0.75), and standard treatments (HR 0.80). Apparent elevated risks with apremilast (HR 1.53) and secukinumab (HR 1.34) vs. adalimumab in the time-to-first-event model were not consistent across sensitivity analyses. Serious infection-related deaths were rare (IR 1.81 per 1,000 person-years).","limitations":"- Elevated risks for apremilast and secukinumab were not replicated in sensitivity analyses, limiting confidence in those signals.\n- Observational registry design introduces potential residual confounding despite inverse probability weighting.\n- Channeling bias is possible, as sicker or higher-risk patients may have been preferentially prescribed certain agents.","practice_takeaway":"For psoriasis patients at elevated infection risk, risankizumab may offer a relative safety advantage over brodalumab, etanercept, and conventional systemic agents. The apparent higher infection risk with apremilast and secukinumab vs. adalimumab should be interpreted cautiously, as it was not robust across sensitivity analyses."}},{"doi":"10.1007/s13555-026-01761-7","pmid":"42068460","title":"A Narrative Review: Do Systemic Drugs Used in the Treatment of Psoriatic Disease Affect Alzheimer’s Disease?","journal_title":"Dermatology and Therapy","journal_issn":"2193-8210","published_at":"2026-05-02T00:00:00.000Z","url":"https://doi.org/10.1007/s13555-026-01761-7","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-10T13:20:36.620Z","updated_at":"2026-05-10T13:20:36.620Z","tags":[{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"brand","value":"Cosentyx","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"brand","value":"Enbrel","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"brand","value":"Humira","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"brand","value":"Otezla","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"brand","value":"Remicade","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"brand","value":"Sotyktu","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"brand","value":"Stelara","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"condition","value":"Psoriasis","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"condition","value":"Psoriatic Arthritis","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"acitretin","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"adalimumab","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"apremilast","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"cyclosporine","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"deucravacitinib","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"etanercept","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"infliximab","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"methotrexate","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"roflumilast","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"secukinumab","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"tofacitinib","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"upadacitinib","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"generic","value":"ustekinumab","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"Conventional Synthetic DMARD","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"IL-12/23 Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"IL-17 Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"IL-23 Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"NSAID","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"Retinoid","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"TNF-Alpha Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"modality","value":"TYK2 Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"warning","value":"Corresponding author (Tsen-Fang Tsai) has disclosed extensive consultant relationships with manufacturers of many drugs discussed in the review.","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"warning","value":"Level of evidence assigned as 5 (narrative review/expert opinion) due to absence of PRISMA methodology, risk-of-bias tools, or meta-analytic synthesis, even though individual cited studies range from Level 1 to Level 5.","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"warning","value":"Several drug-AD associations cited are from studies in rheumatoid arthritis populations, not specifically psoriasis patients; generalizability to psoriatic disease may be limited.","value_numeric":null},{"paper_doi":"10.1007/s13555-026-01761-7","tag_type":"warning","value":"This is a narrative review without formal systematic methods; findings are hypothesis-generating and subject to selection bias in included studies.","value_numeric":null}],"summaries":{"what_studied":"This narrative review examined whether systemic drugs used for psoriatic disease (NSAIDs, methotrexate, cyclosporin, retinoids, PDE4 inhibitors, JAK inhibitors, TYK2 inhibitors, and biologics targeting TNF-α, IL-12/23, IL-17, and IL-23) influence the risk or progression of Alzheimer's disease (AD), using AD as a model for dementia. Literature from PubMed (2015–2025) was synthesized across preclinical, observational, and RCT-level evidence.","key_result":"Most preclinical and observational data suggest antipsoriatic therapies may reduce AD risk. The strongest clinical signal comes from a propensity score–matched cohort (n=1,766) showing biologic therapy for psoriasis was associated with a **53% lower risk of incident dementia** vs. conventional systemic therapy alone. In a large EHR-based study (56 million records), TNF inhibitors (etanercept, adalimumab, infliximab) were linked to markedly reduced AD odds (ORs 0.34, 0.28, and 0.52, respectively; all P<0.0001). However, several large observational studies found the psoriasis–dementia association attenuated or disappeared after adjusting for comorbidities.","limitations":"- Narrative (not systematic) review with no PRISMA flow, risk-of-bias assessment, or quantitative synthesis, limiting reproducibility.\n- Most mechanistic evidence comes from preclinical models (Level 5), with very few adequately powered RCTs in humans.\n- Residual confounding by disease severity, metabolic comorbidities, and medication use cannot be excluded in observational studies.","practice_takeaway":"For older patients with psoriasis, consider early cognitive screening, as shared inflammatory mechanisms may raise dementia risk—especially in those with metabolic comorbidities. Biologic therapy, particularly TNF inhibitors, shows the most consistent signal for possible neuroprotection, but current evidence is hypothesis-generating and should not yet change prescribing solely for dementia prevention."}},{"doi":"10.1016/j.jaad.2026.02.113","pmid":"41949508","title":"Guidelines of care for the management of atopic dermatitis in pediatric patients","journal_title":"Journal of the American Academy of Dermatology","journal_issn":"0190-9622","published_at":"2026-04-07T00:00:00.000Z","url":"https://doi.org/10.1016/j.jaad.2026.02.113","source_score":103,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T17:34:05.456Z","updated_at":"2026-05-07T17:34:05.456Z","tags":[{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Adbry","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Cibinqo","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Dupixent","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Ebglyss","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Eucrisa","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Olumiant","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Opzelura","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Rinvoq","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"brand","value":"Vtama","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"condition","value":"Atopic Dermatitis","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"abrocitinib","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"azathioprine","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"baricitinib","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"crisaborole","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"cyclosporine","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"dupilumab","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"lebrikizumab","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"methotrexate","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"mycophenolate mofetil","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"nemolizumab","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"roflumilast","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"ruxolitinib","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"tapinarof","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"tralokinumab","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"generic","value":"upadacitinib","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"modality","value":"Biologic","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"modality","value":"Conventional Immunosuppressant","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"modality","value":"Phototherapy","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"modality","value":"Topical Calcineurin Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"modality","value":"Topical Corticosteroid","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"study_design","value":"Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"warning","value":"Brand name for nemolizumab (Nemluvio) and lebrikizumab (Ebglyss) inclusion is based on known drug-brand mapping; verify current approvals for pediatric indications.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"warning","value":"Brand name for roflumilast cream (Zoryve) was not explicitly stated in the abstract; brand tag was omitted to avoid speculation.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"warning","value":"No total sample size is reported — this is a guideline/systematic review, not a single trial; sample_size tag was omitted.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.02.113","tag_type":"warning","value":"The DOI publication date (2026-04-07) is in the future relative to the 2014 AAD guidelines it updates, consistent with today's date of May 7, 2026.","value_numeric":null}],"summaries":{"what_studied":"A multidisciplinary AAD workgroup evaluated topical, phototherapy, and systemic treatments for atopic dermatitis (AD) in children and adolescents, using a systematic review and GRADE methodology to update the 2014 AAD guidelines.","key_result":"27 evidence-based recommendations were developed. Strong recommendations support moisturizers, topical corticosteroids, topical calcineurin inhibitors, crisaborole, roflumilast, ruxolitinib, tapinarof, dupilumab, tralokinumab, lebrikizumab, nemolizumab (with topical therapy), upadacitinib, abrocitinib, and baricitinib. Conditional recommendations favor bathing, bleach baths, wet dressings, phototherapy, methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine. Systemic corticosteroids are strongly recommended against.","limitations":"Most RCTs for AD therapies are short in duration, limiting conclusions about long-term efficacy and safety. Evidence is based on best available data at time of review only.","practice_takeaway":"Multiple biologic and JAK inhibitor options now carry strong recommendations for pediatric AD — clinicians should prioritize these over systemic corticosteroids, which are strongly discouraged. Conditional support exists for older immunosuppressants when newer agents are inaccessible."}},{"doi":"10.1007/s13555-025-01631-8","pmid":"41537947","title":"Outcomes in Patients with Psoriasis Following Apremilast Treatment: Results from the German Psoriasis Registry PsoBest","journal_title":"Dermatology and Therapy","journal_issn":"2193-8210","published_at":"2026-01-16T00:00:00.000Z","url":"https://doi.org/10.1007/s13555-025-01631-8","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-16","doi":"10.1007/s13555-025-01631-8","days":"7","issn":"2193-8210","rank":"10","field":"Clinical Medicine","score":"7","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1007/s13555-025-01631-8","title":"Outcomes in Patients with Psoriasis Following Apremilast Treatment: Results from the German Psoriasis Registry PsoBest.","journal":"Dermatology and therapy","methods":"","results":"From January 15, 2015 to June 30, 2020, 595 registry patients were exposed to apremilast; 417 were treated with apremilast monotherapy. Patients taking apremilast had a higher mean age and higher proportions of comorbidities such as cardiovascular or metabolic disease compared with those taking other nonbiologic systemic or biologic drugs. The most common nonserious AEs were drug ineffectiveness (14.1%), diarrhea (9.4%), nausea (7.1%), and headache (6.1%). The highest incidence rates of nonserious and serious AEs of special interest were for infections and infestations per system organ class (8.03/100 patient-years) and malignant or unspecified tumors (2.50/100 patient-years), respectively. Improvements in Dermatology Life Quality Index, patient-defined treatment benefits (Patient Benefit Index), body surface area, and Psoriasis Area and Severity Index were observed after 3, 6, and 12 months of apremilast treatment.","abstract":"$30","keywords":["Apremilast","Dermatology","Psoriasis","Real World","Therapeutics"],"pubmed_id":"41537947","conclusions":"","publication_date":"2026-01-16T00:00:00"},"crossref":{"DOI":"10.1007/s13555-025-01631-8","URL":"https://doi.org/10.1007/s13555-025-01631-8","ISSN":["2193-8210","2190-9172"],"link":[{"URL":"https://link.springer.com/content/pdf/10.1007/s13555-025-01631-8.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/article/10.1007/s13555-025-01631-8","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/content/pdf/10.1007/s13555-025-01631-8.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Outcomes in Patients with Psoriasis Following Apremilast Treatment: Results from the German Psoriasis Registry PsoBest"],"author":[{"given":"Matthias","family":"Augustin","sequence":"first","affiliation":[]},{"given":"Stephan J.","family":"Rustenbach","sequence":"additional","affiliation":[]},{"given":"Ralph","family":"von Kiedrowski","sequence":"additional","affiliation":[]},{"given":"Hamid","family":"Amouzadeh","sequence":"additional","affiliation":[]},{"given":"Kathy","family":"Tran","sequence":"additional","affiliation":[]},{"given":"Myriam","family":"Cordey","sequence":"additional","affiliation":[]},{"given":"Ulrich","family":"Mrowietz","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/100002429","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100002429","name":"Amgen","doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,1,15]]},"member":"297","prefix":"10.1007","source":"Crossref","volume":null,"created":{"date-time":"2026-01-15T14:22:28Z","timestamp":1768486948000,"date-parts":[[2026,1,15]]},"indexed":{"date-time":"2026-01-16T08:18:13Z","timestamp":1768551493248,"date-parts":[[2026,1,16]]},"license":[{"URL":"https://creativecommons.org/licenses/by-nc/4.0","start":{"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000,"date-parts":[[2026,1,15]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by-nc/4.0","start":{"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000,"date-parts":[[2026,1,15]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://link.springer.com/10.1007/s13555-025-01631-8"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"24 September 2025"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":2,"value":"10 December 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":3,"value":"15 January 2026"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"},"order":1},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"},"order":2,"value":"$31"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"},"order":3,"value":"The PsoBest registry was planned and performed under strict rules of patient protection as suggested by German and European laws, the Declaration of Helsinki, and Good Clinical Practice as described in the International Council for Harmonisation Guideline E6. Consent from the ethics committee of the physician’s chamber of the Federal State of Hamburg was obtained (Ethikkommission der Ärztekammer Hamburg, Weidestr. 122b, 22083 Hamburg, Bearbeitungs-Nr. 2805). Signed informed consent was required before study participation."}],"deposited":{"date-time":"2026-01-15T14:22:36Z","timestamp":1768486956000,"date-parts":[[2026,1,15]]},"issn-type":[{"type":"print","value":"2193-8210"},{"type":"electronic","value":"2190-9172"}],"published":{"date-parts":[[2026,1,15]]},"publisher":"Springer Science and Business Media LLC","reference":[{"DOI":null,"key":"1631_CR1","year":"2024","issue":null,"author":"K Hagenström","volume":"22","first-page":"45","unstructured":"Hagenström K, Müller K, Garbe C, Augustin M. Prevalence of psoriasis and psoriatic arthritis in Germany—analysis of claims data. J Dtsch Dermatol Ges. 2024;22:45–54.","article-title":null,"journal-title":"J Dtsch Dermatol Ges","doi-asserted-by":null},{"DOI":"10.1159/000119415","key":"1631_CR2","year":"2008","issue":null,"author":"M Augustin","volume":"216","first-page":"366","unstructured":"Augustin M, Krüger K, Radtke MA, Schwippl I, Reich K. Disease severity, quality of life and health care in plaque-type psoriasis: a multicenter cross-sectional study in Germany. Dermatology. 2008;216:366–72.","article-title":null,"journal-title":"Dermatology","doi-asserted-by":"publisher"},{"DOI":"10.1007/s13555-021-00635-4","key":"1631_CR3","year":"2022","issue":null,"author":"M Lebwohl","volume":"12","first-page":"61","unstructured":"Lebwohl M, Langley RG, Paul C, et al. Evolution of patient perceptions of psoriatic disease: results from the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey. Dermatol Ther (Heidelb). 2022;12:61–78.","article-title":null,"journal-title":"Dermatol Ther (Heidelb)","doi-asserted-by":"publisher"},{"DOI":"10.2340/00015555-0770","key":"1631_CR4","year":"2010","issue":null,"author":"M Augustin","volume":"90","first-page":"147","unstructured":"Augustin M, Reich K, Glaeske G, Schaefer I, Radtke M. Co-morbidity and age-related prevalence of psoriasis: analysis of health insurance data in Germany. Acta Derm Venereol. 2010;90:147–51.","article-title":null,"journal-title":"Acta Derm Venereol","doi-asserted-by":"publisher"},{"DOI":"10.1371/journal.pone.0265741","key":"1631_CR5","year":"2022","issue":null,"author":"J Augustin","volume":"17","first-page":null,"unstructured":"Augustin J, Wolf S, Stephan B, Augustin M, Andrees V. Psoriasis comorbidities in Germany: a population-based study on spatiotemporal variations. PLoS ONE. 2022;17:e0265741.","article-title":null,"journal-title":"PLoS ONE","doi-asserted-by":"publisher"},{"DOI":"10.1111/jdv.19192","key":"1631_CR6","year":"2023","issue":null,"author":"U Mrowietz","volume":"37","first-page":"1731","unstructured":"Mrowietz U, Sümbül M, Gerdes S. Depression, a major comorbidity of psoriatic disease, is caused by metabolic inflammation. J Eur Acad Dermatol Venereol. 2023;37:1731–8.","article-title":null,"journal-title":"J Eur Acad Dermatol Venereol","doi-asserted-by":"publisher"},{"DOI":null,"key":"1631_CR7","year":"2024","issue":null,"author":"U Mrowietz","volume":"121","first-page":"467","unstructured":"Mrowietz U, Lauffer F, Sondermann W, Gerdes S, Sewerin P. Psoriasis as a systemic disease. Dtsch Arztebl Int. 2024;121:467–72.","article-title":null,"journal-title":"Dtsch Arztebl Int","doi-asserted-by":null},{"DOI":null,"key":"1631_CR8","year":"2021","issue":null,"author":"A Nast","volume":"19","first-page":"934","unstructured":"Nast A, Altenburg A, Augustin M, et al. German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 1: treatment goals and treatment recommendations. JDDG J Dtsch Dermatol Ges. 2021;19:934–150.","article-title":null,"journal-title":"JDDG J Dtsch Dermatol Ges","doi-asserted-by":null},{"DOI":"10.1016/j.jaad.2020.02.044","key":"1631_CR9","year":"2020","issue":null,"author":"A Menter","volume":"82","first-page":"1445","unstructured":"Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020;82:1445–86.","article-title":null,"journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":null,"key":"1631_CR10","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Otezla [summary of product characteristics]. Breda, Netherlands: Amgen Europe B.V., 2022.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1007/s13555-021-00658-x","key":"1631_CR11","year":"2022","issue":null,"author":"K Reich","volume":"12","first-page":"203","unstructured":"Reich K, Korge B, Magnolo N, et al. Quality-of-life outcomes, effectiveness and tolerability of apremilast in patients with plaque psoriasis and routine German dermatology care: results from LAPIS-PSO. Dermatol Ther (Heidelb). 2022;12:203–21.","article-title":null,"journal-title":"Dermatol Ther (Heidelb)","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2015.03.049","key":"1631_CR12","year":"2015","issue":null,"author":"K Papp","volume":"73","first-page":"37","unstructured":"Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1]). J Am Acad Dermatol. 2015;73:37–49.","article-title":null,"journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1111/bjd.14164","key":"1631_CR13","year":"2015","issue":null,"author":"C Paul","volume":"173","first-page":"1387","unstructured":"Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2). Br J Dermatol. 2015;173:1387–99.","article-title":null,"journal-title":"Br J Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1111/jdv.16431","key":"1631_CR14","year":"2021","issue":null,"author":"M Augustin","volume":"35","first-page":"123","unstructured":"Augustin M, Kleyn CE, Conrad C, et al. Characteristics and outcomes of patients treated with apremilast in the real world: results from the APPRECIATE study. J Eur Acad Dermatol Venereol. 2021;35:123–34.","article-title":null,"journal-title":"J Eur Acad Dermatol Venereol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ad.2021.05.010","key":"1631_CR15","year":"2021","issue":null,"author":"P Herranz","volume":"112","first-page":"817","unstructured":"Herranz P, Trasobares L, Mateu A, et al. Characterization and outcomes in patients treated with apremilast in routine clinical practice in Spain: results from the APPRECIATE study. Actas Dermosifiliogr (Engl Ed). 2021;112:817–27.","article-title":null,"journal-title":"Actas Dermosifiliogr (Engl Ed)","doi-asserted-by":"publisher"},{"DOI":"10.1007/s12325-021-01981-7","key":"1631_CR16","year":"2022","issue":null,"author":"PD Ghislain","volume":"39","first-page":"1068","unstructured":"Ghislain PD, Lambert J, Hoai XL, et al. Real-life effectiveness of apremilast for the treatment of psoriasis in Belgium: results from the observational OTELO study. Adv Ther. 2022;39:1068–80.","article-title":null,"journal-title":"Adv Ther","doi-asserted-by":"publisher"},{"DOI":"10.1007/s12325-023-02516-y","key":"1631_CR17","year":"2023","issue":null,"author":"C Giofrè","volume":"40","first-page":"3021","unstructured":"Giofrè C, Fabbrocini G, Potenza C, et al. Real-world apremilast use for treatment of plaque psoriasis in Italy: patient perspective, characteristics, and clinical outcomes from the DARWIN study. Adv Ther. 2023;40:3021–37.","article-title":null,"journal-title":"Adv Ther","doi-asserted-by":"publisher"},{"DOI":"10.1007/s13555-023-00933-z","key":"1631_CR18","year":"2023","issue":null,"author":"D Jullien","volume":"13","first-page":"1361","unstructured":"Jullien D, Richard MA, Halioua B, Bessette C, Derancourt C, Bouloc A. The needs of patients with psoriasis and benefits of apremilast in French clinical practice: results from the observational REALIZE study. Dermatol Ther (Heidelb). 2023;13:1361–76.","article-title":null,"journal-title":"Dermatol Ther (Heidelb)","doi-asserted-by":"publisher"},{"DOI":null,"key":"1631_CR19","year":"2014","issue":null,"author":"M Augustin","volume":"12","first-page":"48","unstructured":"Augustin M, Spehr C, Radtke MA, et al. German psoriasis registry PsoBest: objectives, methodology and baseline data. JDDG J Dtsch Dermatol Ges. 2014;12:48–57.","article-title":null,"journal-title":"JDDG J Dtsch Dermatol Ges","doi-asserted-by":null},{"DOI":"10.1007/s40257-023-00783-7","key":"1631_CR20","year":"2023","issue":null,"author":"PJ Mease","volume":"24","first-page":"809","unstructured":"Mease PJ, Hatemi G, Paris M, et al. Apremilast long-term safety up to 5 years from 15 pooled randomized, placebo-controlled studies of psoriasis, psoriatic arthritis, and Behçet’s syndrome. Am J Clin Dermatol. 2023;24:809–20.","article-title":null,"journal-title":"Am J Clin Dermatol","doi-asserted-by":"publisher"},{"DOI":null,"key":"1631_CR21","year":"2008","issue":null,"author":"MK Basra","volume":"159","first-page":"997","unstructured":"Basra MK, Fenech R, Gatt RM, Salek MS, Finlay AY. The dermatology life quality index 1994-2007: a comprehensive review of validation data and clinical results. Br J Dermatol. 2008;159:997–1035.","article-title":null,"journal-title":"Br J Dermatol","doi-asserted-by":null},{"DOI":null,"key":"1631_CR22","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"OTEZLA [prescribing information]. Thousand Oaks, CA: Amgen Inc., 2021.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/j.jaad.2017.01.052","key":"1631_CR23","year":"2017","issue":null,"author":"J Crowley","volume":"77","first-page":"310","unstructured":"Crowley J, Thaçi D, Joly P, et al. Long-term safety and tolerability of apremilast in patients with psoriasis: pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). J Am Acad Dermatol. 2017;77:310-7.e1.","article-title":null,"journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1007/s00403-015-1593-8","key":"1631_CR24","year":"2015","issue":null,"author":"K Reich","volume":"307","first-page":"875","unstructured":"Reich K, Mrowietz U, Radtke MA, et al. Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest. Arch Dermatol Res. 2015;307:875–83.","article-title":null,"journal-title":"Arch Dermatol Res","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2018.11.058","key":"1631_CR25","year":"2019","issue":null,"author":"CA Elmets","volume":"80","first-page":"1073","unstructured":"Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80:1073–113.","article-title":null,"journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.5826/dpc.1204a179","key":"1631_CR26","year":"2022","issue":null,"author":"A Tsentemeidou","volume":"12","first-page":null,"unstructured":"Tsentemeidou A, Sotiriou E, Sideris N, et al. Apremilast in psoriasis patients with serious comorbidities: a case series and systematic review of literature. Dermatol Pract Concept. 2022;12:e2022179.","article-title":null,"journal-title":"Dermatol Pract Concept","doi-asserted-by":"publisher"},{"DOI":"10.33590/emjrheumatol/10314411","key":"1631_CR27","year":"2019","issue":null,"author":"A Chan","volume":"6","first-page":"134","unstructured":"Chan A, Rigler K, Herdman L. Real-world experience of apremilast in treating psoriatic arthritis patients with comorbidities. EMJ Rheumatol. 2019;6:134–9.","article-title":null,"journal-title":"EMJ Rheumatol","doi-asserted-by":"publisher"},{"DOI":null,"key":"1631_CR28","year":"2023","issue":null,"author":"T Heidbrede","volume":"21","first-page":"611","unstructured":"Heidbrede T, Mevius A, Kessel S, Wilke T, Maywald U, Thiem A. Real-world systemic treatment of patients with psoriasis: a retrospective study based on German claims data. JDDG J Dtsch Dermatol Ges. 2023;21:611–9.","article-title":null,"journal-title":"JDDG J Dtsch Dermatol Ges","doi-asserted-by":null},{"DOI":"10.1111/jdv.15804","key":"1631_CR29","year":"2019","issue":null,"author":"AC Fougerousse","volume":"33","first-page":"e476","unstructured":"Fougerousse AC, Maccari F, Beauchet A, et al. Factors that may influence the choice for initiating apremilast or methotrexate treatment for psoriasis in real-world clinical setting. J Eur Acad Dermatol Venereol. 2019;33:e476–8.","article-title":null,"journal-title":"J Eur Acad Dermatol Venereol","doi-asserted-by":"publisher"},{"DOI":"10.1159/000365390","key":"1631_CR30","year":"2015","issue":null,"author":"MK Basra","volume":"230","first-page":"27","unstructured":"Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology. 2015;230:27–33.","article-title":null,"journal-title":"Dermatology","doi-asserted-by":"publisher"}],"short-title":[],"update-policy":"https://doi.org/10.1007/springer_crossmark_policy","alternative-id":["1631"],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"original-title":[],"container-title":["Dermatology and Therapy"],"reference-count":30,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,15]]},"references-count":30,"short-container-title":["Dermatol Ther (Heidelb)"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1007/s13555-025-01631-8","is_oa":true,"title":"Outcomes in Patients with Psoriasis Following Apremilast Treatment: Results from the German Psoriasis Registry PsoBest","updated":"2026-01-18T01:04:10+00:00","published_date":"2026-01-15","best_oa_location":{"url":"https://link.springer.com/content/pdf/10.1007/s13555-025-01631-8.pdf","pmh_id":null,"url_for_pdf":"https://link.springer.com/content/pdf/10.1007/s13555-025-01631-8.pdf","url_for_landing_page":"https://doi.org/10.1007/s13555-025-01631-8"}}},"created_at":"2026-01-20T15:55:50.695Z","updated_at":"2026-01-21T12:05:26.220Z","tags":[{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"brand","value":"Otezla","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"condition","value":"Psoriasis","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"condition","value":"Psoriatic Arthritis","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"generic","value":"apremilast","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"sample_size","value":"n=595","value_numeric":595},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"study_design","value":"Cohort","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"warning","value":"Denominators shrink over time (3, 6, 12 months) due to attrition; interpret later timepoints cautiously.","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"warning","value":"Design is a descriptive observational registry; classifying as a cohort study is approximate.","value_numeric":null},{"paper_doi":"10.1007/s13555-025-01631-8","tag_type":"warning","value":"Population included both psoriasis and psoriatic arthritis; skin outcomes reported are psoriasis-focused.","value_numeric":null}],"summaries":{"what_studied":"Descriptive analysis of German PsoBest registry data (01/15/2015–06/30/2020) on adults with moderate to severe plaque psoriasis or psoriatic arthritis initiating apremilast (safety cohort n=595; monotherapy outcomes cohort n=417), with outcomes assessed at 3, 6, and 12 months.","key_result":"Common nonserious AEs were drug ineffectiveness 14.1%, diarrhea 9.4%, nausea 7.1%, and headache 6.1%; infections had the highest nonserious AE incidence (8.03/100 patient-years), and malignant or unspecified tumors the highest serious AE incidence (2.50/100 patient-years). DLQI improved from 11.1 at baseline to 6.1, 4.7, and 5.3 at 3, 6, and 12 months; mean BSA fell from 22.1% to 8.1% at 12 months; 85.6% achieved PBI ≥1 at 12 months.","limitations":"Observational registry with potential incomplete documentation, selection/recall bias, and attrition reducing sample sizes over time; no between-cohort outcome comparisons were performed. Safety reporting may have been more frequent early after approval.","practice_takeaway":"In routine German care, apremilast improved psoriasis severity and quality of life with a safety profile consistent with labeling. Counsel patients on common GI AEs and set expectations for symptom and QoL gains within 3–6 months."}},{"doi":"10.1001/jamadermatol.2025.2980","pmid":"40833728","title":"Comparative Risk of Infection and Prevalence of Combination Targeted Therapy in Psoriatic Arthritis","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2025-08-20T00:00:00.000Z","url":"https://doi.org/10.1001/jamadermatol.2025.2980","source_score":24,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-11-21","doi":"10.1001/jamadermatol.2025.2980","days":"14","issn":"2168-6068","rank":"9","field":"Clinical Medicine","score":"24","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1001/jamadermatol.2025.2980","title":"Comparative Risk of Infection and Prevalence of Combination Targeted Therapy in Psoriatic Arthritis.","journal":"JAMA dermatology","methods":"","results":"$32","abstract":"$33","keywords":[],"pubmed_id":"40833728","conclusions":"","publication_date":"2025-08-20T00:00:00"},"crossref":{"DOI":"10.1001/jamadermatol.2025.2980","URL":"https://doi.org/10.1001/jamadermatol.2025.2980","ISSN":["2168-6068"],"link":[{"URL":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2837979/jamadermatology_wu_2025_br_250008_1762976624.40521.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1162","type":"journal-article","issue":"11","score":1,"title":["Comparative Risk of Infection and Prevalence of Combination Targeted Therapy in Psoriatic Arthritis"],"author":[{"given":"Alexander","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Texas Southwestern Medical Center, Dallas"}]},{"given":"Arianna","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Yujia","family":"Guo","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Peter O’Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas"}]},{"given":"Jialiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Peter O’Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas"}]},{"given":"Donghan M.","family":"Yang","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Peter O’Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas"}]},{"given":"Lourdes Perez","family":"Chada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Alexis","family":"Ogdie","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia"}]},{"given":"Soumya M.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Medicine and Rheumatology, New York University Langone Health, New York"}]},{"given":"Alice B.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York"}]},{"given":"Jose U.","family":"Scher","sequence":"additional","affiliation":[{"name":"Department of Medicine and Rheumatology, New York University Langone Health, New York"}]},{"given":"Joseph F.","family":"Merola","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Texas Southwestern Medical Center, Dallas"},{"name":"Department of Medicine, Division of Rheumatology, University of Texas Southwestern Medical Center, Dallas"}]}],"issued":{"date-parts":[[2025,11,1]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":"161","created":{"date-time":"2025-08-20T15:00:22Z","timestamp":1755702022000,"date-parts":[[2025,8,20]]},"indexed":{"date-time":"2025-11-19T16:04:18Z","timestamp":1763568258911,"date-parts":[[2025,11,19]]},"subject":[],"abstract":"$34","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamadermatology/fullarticle/2837979"}},"subtitle":[],"deposited":{"date-time":"2025-11-19T16:00:36Z","timestamp":1763568036000,"date-parts":[[2025,11,19]]},"issn-type":[{"type":"print","value":"2168-6068"}],"published":{"date-parts":[[2025,11,1]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.1038/s41572-021-00293-y","key":"dbr250008r1","year":"2021","issue":"1","author":"FitzGerald","volume":"7","first-page":"59","unstructured":null,"article-title":"Psoriatic arthritis.","journal-title":"Nat Rev Dis Primers","doi-asserted-by":"publisher"},{"DOI":"10.1007/s11926-019-0876-z","key":"dbr250008r2","year":"2019","issue":"12","author":"Ritchlin","volume":"21","first-page":"72","unstructured":null,"article-title":"Strategies to improve outcomes in psoriatic arthritis.","journal-title":"Curr Rheumatol Rep","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.det.2024.02.014","key":"dbr250008r3","year":"2024","issue":"3","author":"Wu","volume":"42","first-page":"429","unstructured":null,"article-title":"Prevention of psoriatic arthritis: the need for prospective studies.","journal-title":"Dermatol Clin","doi-asserted-by":"publisher"},{"DOI":"10.1002/art.41765","key":"dbr250008r4","year":"2021","issue":"9","author":"Scher","volume":"73","first-page":"1574","unstructured":null,"article-title":"Moving the goalpost toward remission: the case for combination immunomodulatory therapies in psoriatic arthritis.","journal-title":"Arthritis Rheumatol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.semarthrit.2018.12.003","key":"dbr250008r5","year":"2019","issue":"1","author":"Boleto","volume":"49","first-page":"35","unstructured":null,"article-title":"Safety of combination therapy with two DMARDs in patients with rheumatoid arthritis: a systematic review and meta-analysis.","journal-title":"Semin Arthritis Rheum","doi-asserted-by":"publisher"},{"DOI":"10.1002/art.20221","key":"dbr250008r6","year":"2004","issue":"5","author":"Genovese","volume":"50","first-page":"1412","unstructured":null,"article-title":"Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate.","journal-title":"Arthritis Rheum","doi-asserted-by":"publisher"},{"DOI":"10.1016/S2468-1253(22)00427-7","key":"dbr250008r7","year":"2023","issue":"4","author":"Feagan","volume":"8","first-page":"307","unstructured":null,"article-title":"Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial.","journal-title":"Lancet Gastroenterol Hepatol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jdcr.2019.08.015","key":"dbr250008r8","year":"2019","issue":"10","author":"Thibodeaux","volume":"5","first-page":"928","unstructured":null,"article-title":"Dual biologic therapy for recalcitrant psoriasis and psoriatic arthritis.","journal-title":"JAAD Case Rep","doi-asserted-by":"publisher"},{"DOI":"10.1093/rheumatology/key199","key":"dbr250008r9","year":"2018","issue":"11","author":"De Marco","volume":"57","first-page":"2053","unstructured":null,"article-title":"Combined inhibition of tumour necrosis factor-alpha and interleukin-12/23 for long-standing, refractory psoriatic disease: a differential role for cytokine pathways?","journal-title":"Rheumatology (Oxford)","doi-asserted-by":"publisher"},{"DOI":"10.1111/bjd.14270","key":"dbr250008r10","year":"2016","issue":"5","author":"Gniadecki","volume":"174","first-page":"1145","unstructured":null,"article-title":"Combination of antitumour necrosis factor-a and anti-interleukin-12/23 antibodies in refractory psoriasis and psoriatic arthritis: a long-term case-series observational study.","journal-title":"Br J Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1002/pds.4950","key":"dbr250008r11","year":"2020","issue":"4","author":"Lee","volume":"29","first-page":"404","unstructured":null,"article-title":"Validation of claims-based algorithms for psoriatic arthritis.","journal-title":"Pharmacoepidemiol Drug Saf","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2019.02.014","key":"dbr250008r12","year":"2019","issue":"6","author":"Abignano","volume":"80","first-page":"1796","unstructured":null,"article-title":"A comparison of apremilast monotherapy and combination therapy for psoriatic arthritis in a real-life setting: data from the Leeds Combined Psoriatic Service.","journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2018.04.043","key":"dbr250008r13","year":"2018","issue":"5","author":"Ighani","volume":"79","first-page":"953","unstructured":null,"article-title":"Maintenance of therapeutic response after 1 year of apremilast combination therapy compared with monotherapy for the treatment of plaque psoriasis: a multicenter, retrospective study.","journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1007/s40257-022-00703-1","key":"dbr250008r14","year":"2022","issue":"5","author":"Gyldenløve","volume":"23","first-page":"605","unstructured":null,"article-title":"Combination therapy with apremilast and biologics for psoriasis: a systematic review.","journal-title":"Am J Clin Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.berh.2022.101809","key":"dbr250008r15","year":"2022","issue":"4","author":"Hutton","volume":"36","first-page":null,"unstructured":null,"article-title":"Horizon scan: state-of-the-art therapeutics for psoriatic arthritis.","journal-title":"Best Pract Res Clin Rheumatol","doi-asserted-by":"publisher"}],"short-title":[],"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,1]]}},"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Dermatology"],"published-print":{"date-parts":[[2025,11,1]]},"reference-count":15,"published-online":null,"references-count":15,"short-container-title":["JAMA Dermatol"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1001/jamadermatol.2025.2980","is_oa":false,"title":"Comparative Risk of Infection and Prevalence of Combination Targeted Therapy in Psoriatic Arthritis","updated":"2025-08-22T08:47:48+00:00","published_date":"2025-08-20","best_oa_location":null}},"created_at":"2025-11-23T07:03:49.856Z","updated_at":"2025-12-08T12:24:58.509Z","tags":[{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"condition","value":"Psoriatic Arthritis","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"modality","value":"IL-17 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"modality","value":"TNF Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"sample_size","value":"n=82,399","value_numeric":82399},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"study_design","value":"Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"warning","value":"Follow-up beyond the 3- and 6-month continuous-use windows was unclear.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"warning","value":"The 6-month opportunistic infection relative risk was not estimable, and numerators for incidence rates were not provided.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2025.2980","tag_type":"warning","value":"The exact size and characteristics of the matched control cohort were not reported.","value_numeric":null}],"summaries":{"what_studied":"A retrospective cohort of adults with psoriatic arthritis in MarketScan (2015-2024) evaluated use patterns of combination targeted therapy and compared serious and opportunistic infections requiring inpatient care versus standard therapy using propensity score matching over 3- and 6-month continuous-use windows.","key_result":"Of 82,399 individuals with psoriatic arthritis, 542 used combination therapy for 3 months and 200 for 6 months; most common pairs were a TNF inhibitor with apremilast (34%-37%) and an IL-17 inhibitor with apremilast (27%-29%). Serious infection incidence was 7.38–15.00 per 1000 patients and opportunistic infection 0–1.85 per 1000; no significant risk increase versus standard therapy (PS-matched serious infection RRs: 0.53 [95% CI, 0.17–1.63] at 3 months and 1.50 [0.34–6.65] at 6 months; opportunistic infection RR: 1.00 [0.09–11.02] at 3 months; 6-month RR not applicable).","limitations":"Findings are from commercially insured adults and rely on ICD-10 inpatient codes for infection outcomes. Combination-therapy users and infection events were few, yielding wide confidence intervals and a non-estimable 6-month opportunistic infection risk.","practice_takeaway":"In this claims cohort, combining targeted agents—often a biologic plus apremilast—was used in about 1% of adults with psoriatic arthritis and was not associated with higher hospitalization for serious or opportunistic infections over 3–6 months versus standard therapy. If considering such combinations, counsel that observed infection risk was not higher, but estimates are imprecise and larger studies are needed."}},{"doi":"10.1111/pde.15840","pmid":"39980188","title":"Efficacy and Safety of Once‐Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2–5 Years With Mild‐to‐Moderate Atopic Dermatitis (INTEGUMENT‐PED): A Phase 3 Randomized Controlled Trial","journal_title":"Pediatric Dermatology","journal_issn":"0736-8046","published_at":"2025-02-21T00:00:00.000Z","url":"https://escholarship.org/uc/item/1xh2214j","source_score":67,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-03-24","doi":"10.1111/pde.15840","days":"30","issn":"0736-8046","rank":"5","field":"Clinical Medicine","score":"67","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1111/pde.15840","title":"Efficacy and Safety of Once-Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2-5 Years With Mild-to-Moderate Atopic Dermatitis (INTEGUMENT-PED): A Phase 3 Randomized Controlled Trial.","journal":"Pediatric dermatology","methods":"","results":"Among 437 and 215 patients treated with roflumilast and vehicle, respectively, significantly greater proportions of the roflumilast group achieved Week-4 vIGA-AD Success (25.4% vs. 10.7%; p < 0.0001), EASI-75 (39.4% vs. 20.6%; p < 0.0001), and WI-NRS Success (35.3% vs. 18.0%; nominal p = 0.0002). Improvement in pruritus was observed within 24 h after the first application (nominal p = 0.0014). Treatment-emergent adverse event (TEAE) rates were low in both groups, and 98.9% were mild or moderate. At all timepoints, stinging/burning that caused definite discomfort was reported by ≤ 0.7% of caregivers of patients in the roflumilast group.","abstract":"$35","keywords":["atopic dermatitis","eczema","nonsteroidal topical","pediatrics","pruritus","roflumilast"],"pubmed_id":"39980188","conclusions":"","publication_date":"2025-02-21T00:00:00"},"crossref":{"DOI":"10.1111/pde.15840","URL":"https://doi.org/10.1111/pde.15840","ISSN":["0736-8046","1525-1470"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/pde.15840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"296-304","type":"journal-article","issue":"2","score":1,"title":["Efficacy and Safety of Once‐Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2–5 Years With Mild‐to‐Moderate Atopic Dermatitis (INTEGUMENT‐PED): A Phase 3 Randomized Controlled Trial"],"author":[{"given":"Lawrence F.","family":"Eichenfield","sequence":"first","affiliation":[{"name":"University of California San Diego, La Jolla, California, USA Rady Children's Hospital – San Diego San Diego California USA"}]},{"given":"Rocco","family":"Serrao","sequence":"additional","affiliation":[{"name":"DOCS Dermatology Mason Ohio USA"}]},{"given":"Vimal H.","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada; Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada; Dermatology Research Institute, Calgary, Alberta, Canada; Skin Health & Wellness Centre, Calgary, Alberta, Canada Probity Medical Research Calgary Alberta Canada"}]},{"given":"John C.","family":"Browning","sequence":"additional","affiliation":[{"name":"Texas Dermatology and Laser Specialists San Antonio Texas USA"}]},{"given":"Lisa","family":"Swanson","sequence":"additional","affiliation":[{"name":"Ada West Dermatology Meridian Idaho USA"}]},{"given":"Tracy","family":"Funk","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland Oregon USA"}]},{"given":"Mercedes E.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Pediatric Skin Research, LLC Coral Gables Florida USA"}]},{"given":"Adelaide A.","family":"Hebert","sequence":"additional","affiliation":[{"name":"UTHealth McGovern Medical School Houston Texas USA"}]},{"given":"Mark","family":"Lee","sequence":"additional","affiliation":[{"name":"Progressive Clinical Research San Antonio Texas USA"}]},{"given":"Mark","family":"Boguniewicz","sequence":"additional","affiliation":[{"name":"National Jewish Health Denver Colorado USA"}]},{"given":"Eric L.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland Oregon USA"}]},{"given":"Melissa S.","family":"Seal","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"David","family":"Krupa","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"Diane","family":"Hanna","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"Scott","family":"Snyder","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"Patrick","family":"Burnett","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"David H.","family":"Chu","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"Erin","family":"Almaraz","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"Robert C.","family":"Higham","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]},{"given":"David R.","family":"Berk","sequence":"additional","affiliation":[{"name":"Arcutis Biotherapeutics, Inc. Westlake Village California USA"}]}],"issued":{"date-parts":[[2025,2,20]]},"member":"311","prefix":"10.1111","source":"Crossref","volume":"42","archive":["Portico"],"created":{"date-time":"2025-02-21T06:30:14Z","timestamp":1740119414000,"date-parts":[[2025,2,21]]},"indexed":{"date-time":"2025-07-03T04:04:03Z","timestamp":1751515443868,"date-parts":[[2025,7,3]]},"license":[{"URL":"http://creativecommons.org/licenses/by-nc/4.0/","start":{"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000,"date-parts":[[2025,2,20]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$36","language":"en","relation":{},"resource":{"primary":{"URL":"https://onlinelibrary.wiley.com/doi/10.1111/pde.15840"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2024-10-01"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":2,"value":"2024-11-23"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":3,"value":"2025-02-20"}],"deposited":{"date-time":"2025-07-02T07:58:49Z","timestamp":1751443129000,"date-parts":[[2025,7,2]]},"issn-type":[{"type":"print","value":"0736-8046"},{"type":"electronic","value":"1525-1470"}],"published":{"date-parts":[[2025,2,20]]},"publisher":"Wiley","reference":[{"DOI":"10.1016/S0140-6736(06)69283-0","key":"e_1_2_11_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":"10.1093/bjd/ljad449","key":"e_1_2_11_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":"10.1111/pai.13996","key":"e_1_2_11_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":null,"key":"e_1_2_11_5_1","year":"2023","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1111/bjd.16046","key":"e_1_2_11_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":"10.2340/actadv.v103.6525","key":"e_1_2_11_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":null,"key":"e_1_2_11_8_1","year":"2024","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1124/jpet.116.232819","key":"e_1_2_11_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":"10.1016/j.jid.2024.10.597","key":"e_1_2_11_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":"10.1001/jama.2022.15632","key":"e_1_2_11_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":null,"key":"e_1_2_11_12_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"M.Gooderham J.Bagel J.DuBois et al. “Roflumilast Foam 0.3% for Scalp and Body Psoriasis: A Phase 3 Randomized Clinical Trial ”(2023) Presented at: 25th World Congress of Dermatology Singapore Singapore.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/j.jaad.2023.12.065","key":"e_1_2_11_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":"10.1001/jamadermatol.2024.3121","key":"e_1_2_11_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":"10.1111/bjd.21615","key":"e_1_2_11_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":"10.1034/j.1600-0625.2001.100102.x","key":"e_1_2_11_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":"10.1001/jama.2013.281053","key":"e_1_2_11_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":"10.1080/105294199277860","key":"e_1_2_11_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/ijd.12645","key":"e_1_2_11_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":null,"key":"e_1_2_11_20_1","year":"2024","issue":null,"author":"Simpson E. L.","volume":"191","first-page":null,"unstructured":null,"article-title":"Long‐Term Safety and Effectiveness With Roflumilast Cream 0.15% in Patients ≥ 6 Years of Age With Atopic Dermatitis: A Phase 3 Open‐Label Extension Trial","journal-title":"Dermatitis","doi-asserted-by":null},{"DOI":"10.1016/j.jpeds.2022.04.027","key":"e_1_2_11_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":"10.1024/1012-5302/a000968","key":"e_1_2_11_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":null,"key":"e_1_2_11_23_1","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":"e_1_2_11_24_1","year":"2020","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_11_25_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Open label extension trial of PDE4 inhibition with roflumilast for the management of atopic dermatitis (INTEGUMENT‐OLE) “Clinicaltrials.Gov Identifier: NCT04804605 ”(2024) https://clinicaltrials.gov/study/NCT04804605.","article-title":null,"journal-title":null,"doi-asserted-by":null}],"short-title":[],"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3]]}},"update-policy":"https://doi.org/10.1002/crossmark_policy","alternative-id":["10.1111/pde.15840"],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Pediatric Dermatology"],"published-print":{"date-parts":[[2025,3]]},"reference-count":24,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,2,20]]},"references-count":24,"short-container-title":["Pediatric Dermatology"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1111/pde.15840","is_oa":true,"title":"Efficacy and Safety of Once‐Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2–5 Years With Mild‐to‐Moderate Atopic Dermatitis (INTEGUMENT‐PED): A Phase 3 Randomized Controlled Trial","updated":"2025-09-06T02:51:56+00:00","published_date":"2025-02-20","best_oa_location":{"url":"https://escholarship.org/uc/item/1xh2214j","pmh_id":"oai:escholarship.org:ark:/13030/qt1xh2214j","url_for_pdf":null,"url_for_landing_page":"https://escholarship.org/uc/item/1xh2214j"}}},"created_at":"2025-09-19T22:40:11.496Z","updated_at":"2025-09-19T22:40:38.622Z","tags":[{"paper_doi":"10.1111/pde.15840","tag_type":"age_group","value":"child","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"condition","value":"Atopic Dermatitis","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"generic","value":"roflumilast","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"sample_size","value":"n=652","value_numeric":652},{"paper_doi":"10.1111/pde.15840","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"warning","value":"Minor discrepancy in roflumilast group size (436 vs 437) across sections; tables report n=437.","value_numeric":null},{"paper_doi":"10.1111/pde.15840","tag_type":"warning","value":"Some itch-related p-values are nominal and may not be multiplicity-adjusted.","value_numeric":null}],"summaries":{"what_studied":"A 4-week, Phase 3 double-blind, vehicle-controlled randomized trial compared once-daily roflumilast cream 0.05% with vehicle in children aged 2–5 years with mild-to-moderate atopic dermatitis (2:1 randomization across 109 sites).","key_result":"At Week 4, vIGA-AD Success occurred in 25.4% with roflumilast vs 10.7% with vehicle (p<0.0001); EASI-75 was 39.4% vs 20.6% (p<0.0001); WI-NRS Success among those with baseline ≥4 was 35.3% vs 18.0% (nominal p=0.0002), with pruritus improvement within 24 h (nominal p=0.0014). TEAEs were low and 98.9% were mild or moderate; application-site stinging/burning causing definite discomfort was reported by ≤0.7% with roflumilast.","limitations":"Short treatment duration (4 weeks); no active comparator; WI-NRS is not validated for ages 2–5 years.","practice_takeaway":"In toddlers with mild-to-moderate atopic dermatitis, once-daily roflumilast 0.05% improved signs and itch by Week 4—and as early as 24 hours—while showing low rates of mostly mild AEs and local tolerability comparable to vehicle over 4 weeks."}},{"doi":"10.1001/jamadermatol.2023.4990","pmid":"38117526","title":"Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2023-12-20T00:00:00.000Z","url":"https://doi.org/10.1001/jamadermatol.2023.4990","source_score":86,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2024-01-18","doi":"10.1001/jamadermatol.2023.4990","days":"30","issn":"2168-6068","rank":"5","field":"Clinical Medicine","score":"86","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1001/jamadermatol.2023.4990","title":"Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis: A Randomized Clinical Trial.","journal":"JAMA dermatology","methods":"","results":"$37","abstract":"$38","keywords":[],"pubmed_id":"38117526","conclusions":"","publication_date":"2023-12-20T00:00:00"},"crossref":{"DOI":"10.1001/jamadermatol.2023.4990","URL":"https://doi.org/10.1001/jamadermatol.2023.4990","ISSN":["2168-6068"],"link":[{"URL":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2812729/jamadermatology_eichenfield_2023_oi_230061_1707346940.68612.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"156","type":"journal-article","issue":"2","score":1,"title":["Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis"],"author":[{"given":"Lawrence F.","family":"Eichenfield","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of California, San Diego, School of Medicine"},{"name":"Department of Pediatrics, University of California, San Diego, School of Medicine"},{"name":"Division of Pediatric and Adolescent Dermatology, Rady Children’s Hospital–San Diego, San Diego, California"}]},{"given":"Sanela","family":"Tarabar","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Cambridge, Massachusetts"}]},{"given":"Seth","family":"Forman","sequence":"additional","affiliation":[{"name":"ForCare Clinical Research, Tampa, Florida"}]},{"given":"Alfonso","family":"García-Bello","sequence":"additional","affiliation":[{"name":"Renaissance Research and Medical Group, Cape Coral, Florida"}]},{"given":"Gang","family":"Feng","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Cambridge, Massachusetts"}]},{"given":"Gerald","family":"Fetterly","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Cambridge, Massachusetts"}]},{"given":"Ping","family":"Mahling","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Cambridge, Massachusetts"}]},{"given":"Elena","family":"Peeva","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Cambridge, Massachusetts"}]},{"given":"Michael S.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Cambridge, Massachusetts"}]},{"given":"Deepa E.","family":"Chandra","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Cambridge, Massachusetts"}]}],"issued":{"date-parts":[[2024,2,1]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":"160","created":{"date-time":"2023-12-20T16:02:49Z","timestamp":1703088169000,"date-parts":[[2023,12,20]]},"indexed":{"date-time":"2025-09-04T13:15:25Z","timestamp":1756991725355,"date-parts":[[2025,9,4]]},"subject":[],"abstract":"$39","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamadermatology/fullarticle/2812729"}},"subtitle":["A Randomized Clinical Trial"],"deposited":{"date-time":"2024-02-21T16:02:18Z","timestamp":1708531338000,"date-parts":[[2024,2,21]]},"issn-type":[{"type":"print","value":"2168-6068"}],"published":{"date-parts":[[2024,2,1]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.1136/bmj.m1590","key":"doi230061r1","year":"2020","issue":null,"author":"Parisi","volume":"369","first-page":"m1590","unstructured":null,"article-title":"National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study.","journal-title":"BMJ","doi-asserted-by":"publisher"},{"DOI":"10.1080/09546634.2019.1655137","key":"doi230061r2","year":"2020","issue":"8","author":"Cork","volume":"31","first-page":"801","unstructured":null,"article-title":"Atopic dermatitis epidemiology and unmet need in the United Kingdom.","journal-title":"J Dermatolog Treat","doi-asserted-by":"publisher"},{"DOI":"10.1007/s13555-019-0280-7","key":"doi230061r3","year":"2019","issue":"1","author":"Draelos","volume":"9","first-page":"71","unstructured":null,"article-title":"Tolerability of topical treatments for atopic dermatitis.","journal-title":"Dermatol Ther (Heidelb)","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2020.07.087","key":"doi230061r4","year":"2021","issue":"2","author":"Elmets","volume":"84","first-page":"432","unstructured":null,"article-title":"Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.","journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2014.03.023","key":"doi230061r5","year":"2014","issue":"1","author":"Eichenfield","volume":"71","first-page":"116","unstructured":null,"article-title":"Guidelines of care for the management of atopic dermatitis: section 2: management and treatment of atopic dermatitis with topical therapies.","journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.2340/00015555-2051","key":"doi230061r6","year":"2015","issue":"5","author":"Åkerström","volume":"95","first-page":"587","unstructured":null,"article-title":"Comparison of moisturizing creams for the prevention of atopic dermatitis relapse: a randomized double-blind controlled multicentre clinical trial.","journal-title":"Acta Derm Venereol","doi-asserted-by":"publisher"},{"DOI":"10.3390/diagnostics11112090","key":"doi230061r7","year":"2021","issue":"11","author":"Moniaga","volume":"11","first-page":"2090","unstructured":null,"article-title":"The pathology of type 2 inflammation–associated itch in atopic dermatitis.","journal-title":"Diagnostics (Basel)","doi-asserted-by":"publisher"},{"DOI":"10.3390/ijms222312793","key":"doi230061r8","year":"2021","issue":"23","author":"Singh","volume":"22","first-page":"12793","unstructured":null,"article-title":"The cytokine mediated molecular pathophysiology of psoriasis and its clinical implications.","journal-title":"Int J Mol Sci","doi-asserted-by":"publisher"},{"DOI":"10.3389/fphar.2018.01048","key":"doi230061r9","year":"2018","issue":null,"author":"Li","volume":"9","first-page":"1048","unstructured":null,"article-title":"Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases.","journal-title":"Front Pharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1001/jama.2022.15632","key":"doi230061r10","year":"2022","issue":"11","author":"Lebwohl","volume":"328","first-page":"1073","unstructured":null,"article-title":"Effect of roflumilast cream vs vehicle cream on chronic plaque psoriasis: the DERMIS-1 and DERMIS-2 randomized clinical trials.","journal-title":"JAMA","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2015.03.049","key":"doi230061r11","year":"2015","issue":"1","author":"Papp","volume":"73","first-page":"37","unstructured":null,"article-title":"Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1).","journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1038/s41573-021-00266-6","key":"doi230061r12","year":"2022","issue":"1","author":"Bieber","volume":"21","first-page":"21","unstructured":null,"article-title":"Atopic dermatitis: an expanding therapeutic pipeline for a complex disease.","journal-title":"Nat Rev Drug Discov","doi-asserted-by":"publisher"},{"DOI":"10.1001/jama.2013.281053","key":"doi230061r13","year":"2013","issue":"20","author":"World Medical Association","volume":"310","first-page":"2191","unstructured":null,"article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.","journal-title":"JAMA","doi-asserted-by":"publisher"},{"DOI":"10.1080/105294199277860","key":"doi230061r14","year":"1998","issue":"2","author":"Dixon","volume":"6","first-page":"65","unstructured":null,"article-title":"The International Conference on Harmonization Good Clinical Practice guideline.","journal-title":"Qual Assur","doi-asserted-by":"publisher"},{"DOI":"10.1111/biom.1999.55.issue-4","key":"doi230061r15","year":"1999","issue":"4","author":"Chan","volume":"55","first-page":"1202","unstructured":null,"article-title":"Test-based exact confidence intervals for the difference of two binomial proportions.","journal-title":"Biometrics","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaad.2016.05.046","key":"doi230061r16","year":"2016","issue":"3","author":"Paller","volume":"75","first-page":"494","unstructured":null,"article-title":"Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults.","journal-title":"J Am Acad Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.36849/JDD","key":"doi230061r17","year":"2023","issue":"2","author":"Gooderham","volume":"22","first-page":"139","unstructured":null,"article-title":"The safety and efficacy of roflumilast cream 0.15% and 0.05% in atopic dermatitis: phase 2 proof-of-concept study.","journal-title":"J Drugs Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1186/s12910-019-0395-5","key":"doi230061r18","year":"2019","issue":"1","author":"Strzebonska","volume":"20","first-page":"58","unstructured":null,"article-title":"Umbrella and basket trials in oncology: ethical challenges.","journal-title":"BMC Med Ethics","doi-asserted-by":"publisher"},{"DOI":null,"key":"doi230061r19","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"FDA approves Arcutis’ ZORYVE™ (Roflumilast) cream 0.3% for the treatment of plaque psoriasis in individuals age 12 and older. Press release. Arcutis Biotherapeutics. 2022. Accessed July 29, 2022. https://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-3-for-the-treatment-of-plaque-psoriasis-in-individuals-age-12-and-older/","article-title":null,"journal-title":null,"doi-asserted-by":null}],"short-title":[],"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Dermatology"],"published-print":{"date-parts":[[2024,2,1]]},"reference-count":19,"published-online":null,"references-count":19,"short-container-title":["JAMA Dermatol"],"is-referenced-by-count":10},"unpaywall":{"doi":"10.1001/jamadermatol.2023.4990","is_oa":true,"title":"Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis","updated":"2025-07-30T00:59:52+00:00","published_date":"2023-12-20","best_oa_location":{"url":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2812729/jamadermatology_eichenfield_2023_oi_230061_1707346940.68612.pdf","pmh_id":null,"url_for_pdf":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2812729/jamadermatology_eichenfield_2023_oi_230061_1707346940.68612.pdf","url_for_landing_page":"https://doi.org/10.1001/jamadermatol.2023.4990"}}},"created_at":"2025-09-20T09:19:29.896Z","updated_at":"2025-09-20T17:26:01.321Z","tags":[{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"condition","value":"Atopic Dermatitis","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"condition","value":"Plaque Psoriasis","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"sample_size","value":"n=104","value_numeric":104},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"warning","value":"Confidence intervals were reported at 90%, not 95%.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"warning","value":"The treatment period was only 6 weeks, limiting durability and safety conclusions.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2023.4990","tag_type":"warning","value":"Two conditions were studied within one trial; subgroup sizes were small, especially psoriasis (n=34).","value_numeric":null}],"summaries":{"limitations":"Short, 6-week phase 2a study with a total n=104 and a small psoriasis cohort (n=34). Only one concentration (0.01%) was tested, and results were reported with 90% CIs rather than 95% CIs.","what_studied":"A phase 2a randomized, double-blind trial at 34 sites in 4 countries tested once-daily PF-07038124 0.01% ointment vs vehicle for 6 weeks in adults (18–70 years) with mild to moderate atopic dermatitis (5%–20% BSA) or plaque psoriasis (5%–15% BSA). The primary outcome was percent change from baseline in EASI (AD) or PASI (psoriasis) at week 6.","key_result":"At week 6, PF-07038124 improved EASI in AD more than vehicle (LS mean CFB −74.9% vs −35.5%; difference −39.4% [90% CI −58.8% to −20.1%]; P<.001) and improved PASI in psoriasis more than vehicle (−4.8 vs 0.1; difference −4.9 [90% CI −7.0 to −2.8]; P<.001).","practice_takeaway":"Once-daily topical PF-07038124 0.01% outperformed vehicle at 6 weeks in mild to moderate AD and plaque psoriasis. TEAEs were similar to vehicle (AD: 25.0% vs 26.5%; psoriasis: 17.6% vs 35.3%), with no application site reactions on PF-07038124."}},{"doi":"10.1111/jdv.18818","pmid":"36527389","title":"Pharmacology of orismilast, a potent and selective PDE4 inhibitor","journal_title":"Journal of the European Academy of Dermatology and Venereology","journal_issn":"0926-9959","published_at":"2022-12-18T00:00:00.000Z","url":"https://doi.org/10.1111/jdv.18818","source_score":379,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2023-02-03","doi":"10.1111/jdv.18818","days":"30","issn":"0926-9959","rank":"2","field":"Clinical Medicine","score":"379","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1111/jdv.18818","title":"Pharmacology of orismilast, a potent and selective PDE4 inhibitor.","journal":"Journal of the European Academy of Dermatology and Venereology : JEADV","methods":"","results":"Orismilast selectively inhibited PDE4 and demonstrated potent inhibition of PDE4B and PDE4D subtype splice variants in vitro. Orismilast inhibited whole blood and PBMC production of tumour necrosis factor α (TNFα), and the secretion of T-helper (Th)1 (TNFα and IFNγ), Th17 (IL-22 and IL-23), and Th2 (IL-4, IL-5, and IL-13) related cytokines in PBMC. In vivo, 10 and 30 mg/kg doses of orismilast significantly reduced ear thickness and inflammation markers (p < 0.0001, respectively).","abstract":"$3a","keywords":[],"pubmed_id":"36527389","conclusions":"Orismilast displayed selective and potent PDE4 inhibition and broad-spectrum anti-inflammatory activity in several pre-clinical models. The results of the study support clinical development of oral orismilast as a novel treatment option for CISD including psoriasis, atopic dermatitis, and hidradenitis suppurativa.","publication_date":"2022-12-18T00:00:00"},"crossref":{"DOI":"10.1111/jdv.18818","URL":"https://doi.org/10.1111/jdv.18818","ISSN":["0926-9959","1468-3083"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.18818","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdv.18818","content-type":"application/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.18818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"721-729","type":"journal-article","issue":"4","score":1,"title":["Pharmacology of orismilast, a potent and selective PDE4 inhibitor"],"author":[{"given":"Jonathan I.","family":"Silverberg","sequence":"first","affiliation":[{"name":"George Washington University School of Medicine and Health Sciences District of Columbia Washington USA"}]},{"given":"Lars E.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University (LMU) Munich, Munich, Germany. Dr. Philip Frost, Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Florida Miami USA"}]},{"given":"Richard B.","family":"Warren","sequence":"additional","affiliation":[{"name":"Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre The University of Manchester Manchester UK"}]},{"given":"Bruce","family":"Strober","sequence":"additional","affiliation":[{"name":"Yale University and Central Connecticut Dermatology Connecticut Cromwell USA"}]},{"given":"Kim","family":"Kjøller","sequence":"additional","affiliation":[{"name":"UNION therapeutics, A/S Hellerup Denmark"}]},{"given":"Morten O. A.","family":"Sommer","sequence":"additional","affiliation":[{"name":"UNION therapeutics, A/S Hellerup Denmark"},{"name":"Novo Nordisk Foundation Center for Biosustainability Technical University of Denmark (DTU) Kongens Lyngby Denmark"}]},{"given":"Philippe","family":"Andres","sequence":"additional","affiliation":[{"name":"UNION therapeutics, A/S Hellerup Denmark"}]},{"given":"Jakob","family":"Felding","sequence":"additional","affiliation":[{"name":"UNION therapeutics, A/S Hellerup Denmark"}]},{"given":"Anne","family":"Weiss","sequence":"additional","affiliation":[{"name":"UNION therapeutics, A/S Hellerup Denmark"}]},{"given":"Deniz","family":"Tutkunkardas","sequence":"additional","affiliation":[{"name":"UNION therapeutics, A/S Hellerup Denmark"}]},{"given":"Tine","family":"Skak‐Nielsen","sequence":"additional","affiliation":[{"name":"LEO Pharma A/S Ballerup Denmark"}]},{"given":"Emma","family":"Guttman","sequence":"additional","affiliation":[{"name":"Department of Dermatology Icahn School of Medicine at Mount Sinai New York New York USA"}]}],"issued":{"date-parts":[[2023,1,18]]},"member":"311","prefix":"10.1111","source":"Crossref","volume":"37","archive":["Portico"],"created":{"date-time":"2022-12-17T13:18:25Z","timestamp":1671283105000,"date-parts":[[2022,12,17]]},"indexed":{"date-time":"2025-09-20T20:38:27Z","timestamp":1758400707015,"date-parts":[[2025,9,20]]},"license":[{"URL":"http://creativecommons.org/licenses/by-nc/4.0/","start":{"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000,"date-parts":[[2023,1,18]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$3b","language":"en","relation":{},"resource":{"primary":{"URL":"https://onlinelibrary.wiley.com/doi/10.1111/jdv.18818"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2022-08-18"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":1,"value":"2022-11-22"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":2,"value":"2023-01-18"}],"deposited":{"date-time":"2023-09-20T12:11:55Z","timestamp":1695211915000,"date-parts":[[2023,9,20]]},"issn-type":[{"type":"print","value":"0926-9959"},{"type":"electronic","value":"1468-3083"}],"published":{"date-parts":[[2023,1,18]]},"publisher":"Wiley","reference":[{"DOI":"10.1001/jamadermatol.2021.2007","key":"e_1_2_9_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.jid.2018.08.028","key":"e_1_2_9_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":"10.1177/2040622319830646","key":"e_1_2_9_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":null,"key":"e_1_2_9_5_1","year":"2019","issue":"12","author":"Psomadakis CE","volume":"12","first-page":"28","unstructured":null,"article-title":"New and emerging topical therapies for psoriasis and atopic dermatitis","journal-title":"J Clin Aesthet Dermatol","doi-asserted-by":null},{"DOI":"10.1080/09546634.2020.1729335","key":"e_1_2_9_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":null,"key":"e_1_2_9_7_1","year":"2018","issue":"4","author":"Aldredge LM","volume":"10","first-page":"189","unstructured":null,"article-title":"Manifestations and management of difficult‐to‐treat psoriasis","journal-title":"JDNA","doi-asserted-by":null},{"DOI":"10.1007/s13555-020-00409-4","key":"e_1_2_9_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":"10.1101/cshperspect.a005926","key":"e_1_2_9_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":null,"key":"e_1_2_9_10_1","year":"2016","issue":"1","author":"Levy J","volume":"7","first-page":"1000326","unstructured":null,"article-title":"Cyclic adenosine monophosphate signalling in inflammatory skin disease","journal-title":"J Clin Exp Dermatol Res","doi-asserted-by":null},{"DOI":"10.1371/journal.pone.0121725","key":"e_1_2_9_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":"10.4049/jimmunol.178.8.4820","key":"e_1_2_9_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":"10.1016/j.cellsig.2016.01.007","key":"e_1_2_9_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":"10.2174/1381612823666170214105651","key":"e_1_2_9_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":"10.1001/archdermatol.2012.812","key":"e_1_2_9_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.cyto.2014.12.014","key":"e_1_2_9_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":"10.3390/ijms19103086","key":"e_1_2_9_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":"10.1007/s40268-019-00284-1","key":"e_1_2_9_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":"10.1056/NEJMoa2000073","key":"e_1_2_9_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":"10.1016/j.jaad.2015.03.049","key":"e_1_2_9_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":"10.2147/COPD.S89849","key":"e_1_2_9_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":null,"key":"e_1_2_9_22_1","year":"2019","issue":"2","author":"Woo TE","volume":"24","first-page":"4","unstructured":null,"article-title":"Crisaborole 2% ointment (Eucrisa) for atopic dermatitis","journal-title":"Skin Therapy Lett","doi-asserted-by":null},{"DOI":null,"key":"e_1_2_9_23_1","year":"2021","issue":null,"author":"PR Newswire","volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_9_24_1","year":"2010","issue":null,"author":"Giembycz MA","volume":"4","first-page":"147","unstructured":null,"article-title":"Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD","journal-title":"Drug dDes Devel Ther","doi-asserted-by":null},{"DOI":null,"key":"e_1_2_9_25_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"GlobeNewswire.FDA Approves Arcutis' ZORYVE™ (Roflumilast) Cream 0.3% For the Treatment of Plaque Psoriasis in Individuals Age 12 and Older. Available from:https://www.globenewswire.com/news‐release/2022/07/29/2488966/0/en/FDA‐Approves‐Arcutis‐ZORYVE‐Roflumilast‐Cream‐0‐3‐For‐the‐Treatment‐of‐Plaque‐Psoriasis‐in‐Individuals‐Age‐12‐and‐Older.html","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.3389/fphar.2018.01048","key":"e_1_2_9_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":null,"key":"e_1_2_9_27_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"ClinicalTrials.gov. Identifier NCT02496546 An Explorative Trial Evaluating the Effect of LEO 32731 Cream in Adults With Mild to Moderate Atopic Dermatitis (AD).2017.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_9_28_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"ClinicalTrials.gov. Identifier: NCT04982432 Orismilast for the Treatment of Mild to Severe Hidradenitis Suppurativa (OSIRIS)2021.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_9_29_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"ClinicalTrials.gov. Study to Assess the Efficacy and Safety of Orismilast in Psoriasis (IASOS).2022.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1021/bi00778a018","key":"e_1_2_9_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":"10.1016/j.jaci.2019.06.047","key":"e_1_2_9_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.cellsig.2014.05.014","key":"e_1_2_9_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"},{"DOI":"10.1016/j.jdermsci.2019.09.003","key":"e_1_2_9_33_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":"10.1615/CritRevEukarGeneExpr.v20.i2.10","key":"e_1_2_9_34_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":null,"key":"e_1_2_9_35_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Otelza [package insert].Celgene Corporation summit (NJ): Celgene Corporation;2019.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1038/s41573-021-00266-6","key":"e_1_2_9_36_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/exd.14451","key":"e_1_2_9_37_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.2016.08.029","key":"e_1_2_9_38_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.2015.09.001","key":"e_1_2_9_39_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":"4","published-print":{"date-parts":[[2023,4]]}},"update-policy":"https://doi.org/10.1002/crossmark_policy","alternative-id":["10.1111/jdv.18818"],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"published-print":{"date-parts":[[2023,4]]},"reference-count":38,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2023,1,18]]},"references-count":38,"short-container-title":["Acad Dermatol Venereol"],"is-referenced-by-count":26},"unpaywall":{"doi":"10.1111/jdv.18818","is_oa":true,"title":"Pharmacology of orismilast, a potent and selective PDE4 inhibitor","updated":"2025-08-17T18:46:03+00:00","published_date":"2022-12-17","best_oa_location":{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.18818","pmh_id":null,"url_for_pdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.18818","url_for_landing_page":"https://doi.org/10.1111/jdv.18818"}}},"created_at":"2025-09-22T07:56:22.026Z","updated_at":"2025-09-22T14:20:55.574Z","tags":[{"paper_doi":"10.1111/jdv.18818","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"condition","value":"Atopic Dermatitis","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"condition","value":"Hidradenitis Suppurativa","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"condition","value":"Psoriasis","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"generic","value":"orismilast","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"study_design","value":"Preclinical Study","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"warning","value":"Apremilast was used as a comparator only in select in vitro/ex vivo assays, not in vivo.","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"warning","value":"Mixed in vitro, ex vivo, and murine experiments; not a clinical trial.","value_numeric":null},{"paper_doi":"10.1111/jdv.18818","tag_type":"warning","value":"Total sample size is unclear across experiments; the in vivo arm randomized 44 mice with 4 naïve controls.","value_numeric":null}],"summaries":{"what_studied":"Evaluated orismilast’s PDE selectivity/potency and anti-inflammatory effects across in vitro PDE1–11 and PDE4 splice-variant assays, ex vivo human whole blood/PBMC cytokine assays (with apremilast as comparator), and an in vivo murine chronic oxazolone ear inflammation model dosed orally at 10 or 30 mg/kg.","key_result":"Orismilast potently inhibited PDE4B/D variants (IC50 3–16 nmol/L) with lower potency for PDE4C2 (104 nmol/L), and more strongly suppressed TNFα than apremilast in PBMC (IC50 10 vs 52 nmol/L; n=3 donors) and whole blood (30 vs 432 nmol/L; n=8–9). In mice, 10 and 30 mg/kg reduced ear thickness over time (p<0.0001), with 30 mg/kg showing AUC 3.4 day×mm versus dexamethasone 2 mg/kg at 2.7 day×mm, and both doses lowered ear-tissue IL-1β, IL-4, IL-5, TNFα, IFNγ, and mKC; mean serum levels were 423 and 1009 ng/mL at 10 and 30 mg/kg.","limitations":"Findings are preclinical; the chronic oxazolone murine model may not mirror human psoriasis, atopic dermatitis, or hidradenitis suppurativa. Ex vivo assays used few human donors (PBMC n=3; whole blood n=8–9; broad cytokine panel n=4). Studies were industry-sponsored with multiple author conflicts of interest reported.","practice_takeaway":"No change in clinical practice. These preclinical data support continued clinical testing of oral orismilast as a selective PDE4 inhibitor with broad cytokine suppression; await results from patient trials."}},{"doi":"10.1111/jdv.18812","pmid":"36478476","title":"Oral orismilast: Efficacy and safety in moderate‐to‐severe psoriasis and development of modified release tablets","journal_title":"Journal of the European Academy of Dermatology and Venereology","journal_issn":"0926-9959","published_at":"2022-12-09T00:00:00.000Z","url":"https://doi.org/10.1111/jdv.18812","source_score":375,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2023-02-03","doi":"10.1111/jdv.18812","days":"30","issn":"0926-9959","rank":"3","field":"Clinical Medicine","score":"375","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1111/jdv.18812","title":"Oral orismilast: Efficacy and safety in moderate-to-severe psoriasis and development of modified release tablets.","journal":"Journal of the European Academy of Dermatology and Venereology : JEADV","methods":"","results":"In the phase 2a trial, treatment with orismilast IR significantly improved the mean Psoriasis Area Severity Index score at week 16 compared to placebo. The phase 1 trial revealed comparable PK properties of the orismilast MR and IR formulations, with participants in the orismilast MR group experiencing fewer GI-related AEs than those receiving orismilast IR (16.7% vs. 33.3%).","abstract":"$3c","keywords":[],"pubmed_id":"36478476","conclusions":"Orismilast IR displayed higher efficacy compared to placebo in patients with moderate-to-severe psoriasis at week 16. Orismilast MR had similar PK properties and fewer GI disorders compared to the IR formulation in healthy participants. Future development of orismilast will be based on the MR formulation.","publication_date":"2022-12-09T00:00:00"},"crossref":{"DOI":"10.1111/jdv.18812","URL":"https://doi.org/10.1111/jdv.18812","ISSN":["0926-9959","1468-3083"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.18812","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdv.18812","content-type":"application/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.18812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"711-720","type":"journal-article","issue":"4","score":1,"title":["Oral orismilast: Efficacy and safety in moderate‐to‐severe psoriasis and development of modified release tablets"],"author":[{"given":"Richard B.","family":"Warren","sequence":"first","affiliation":[{"name":"Dermatology Centre Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester Manchester UK"}]},{"given":"Bruce","family":"Strober","sequence":"additional","affiliation":[{"name":"Yale University and Central Connecticut Dermatology Connecticut New Haven USA"}]},{"given":"Jonathan I.","family":"Silverberg","sequence":"additional","affiliation":[{"name":"George Washington University School of Medicine and Health Sciences Washington District of Columbia USA"}]},{"given":"Emma","family":"Guttman","sequence":"additional","affiliation":[{"name":"Department of Dermatology Icahn School of Medicine at Mount Sinai New York New York USA"}]},{"given":"Philippe","family":"Andres","sequence":"additional","affiliation":[{"name":"UNION therapeutics A/S Hellerup Denmark"}]},{"given":"Jakob","family":"Felding","sequence":"additional","affiliation":[{"name":"UNION therapeutics A/S Hellerup Denmark"}]},{"given":"Deniz","family":"Tutkunkardas","sequence":"additional","affiliation":[{"name":"UNION therapeutics A/S Hellerup Denmark"}]},{"given":"Kim","family":"Kjøller","sequence":"additional","affiliation":[{"name":"UNION therapeutics A/S Hellerup Denmark"}]},{"given":"Morten O. A.","family":"Sommer","sequence":"additional","affiliation":[{"name":"UNION therapeutics A/S Hellerup Denmark"},{"name":"Novo Nordisk Foundation Center for Biosustainability Technical University of Denmark Kongens Lyngby Denmark"}]},{"given":"Lars E.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy University Hospital, Ludwig Maximilian University (LMU) Munich Munich Germany"},{"name":"Dr. Philip Frost, Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami Florida USA"}]}],"funder":[{"id":[{"id":"10.13039/501100009708","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100009708","name":"Novo Nordisk Fonden","award":["NNF20CC0035580"],"doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2023,1,18]]},"member":"311","prefix":"10.1111","source":"Crossref","volume":"37","archive":["Portico"],"created":{"date-time":"2022-12-07T21:44:08Z","timestamp":1670449448000,"date-parts":[[2022,12,7]]},"indexed":{"date-time":"2025-09-20T20:42:49Z","timestamp":1758400969188,"date-parts":[[2025,9,20]]},"license":[{"URL":"http://creativecommons.org/licenses/by-nc-nd/4.0/","start":{"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000,"date-parts":[[2023,1,18]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$3d","language":"en","relation":{},"resource":{"primary":{"URL":"https://onlinelibrary.wiley.com/doi/10.1111/jdv.18812"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2022-08-18"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":1,"value":"2022-11-21"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":2,"value":"2023-01-18"}],"deposited":{"date-time":"2023-09-20T12:11:36Z","timestamp":1695211896000,"date-parts":[[2023,9,20]]},"issn-type":[{"type":"print","value":"0926-9959"},{"type":"electronic","value":"1468-3083"}],"published":{"date-parts":[[2023,1,18]]},"publisher":"Wiley","reference":[{"DOI":"10.1016/S0140-6736(07)61128-3","key":"e_1_2_10_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":"10.1146/annurev.immunol.021908.132710","key":"e_1_2_10_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":"10.1084/jem.20041257","key":"e_1_2_10_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/j.cellsig.2016.01.007","key":"e_1_2_10_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":"10.1038/sj.bjp.0702387","key":"e_1_2_10_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":"10.1038/sj.bjp.0702911","key":"e_1_2_10_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":"10.1001/archdermatol.2012.812","key":"e_1_2_10_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":"10.1007/s40257-022-00712-0","key":"e_1_2_10_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":"10.1056/NEJMoa2000073","key":"e_1_2_10_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":"10.3389/fphar.2021.740803","key":"e_1_2_10_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":null,"key":"e_1_2_10_12_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"ClinicalTrials.gov.Identifier NCT02496546 an explorative trial evaluating the effect of LEO 32731 cream in adults with mild to moderate atopic dermatitis (AD).2017.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_10_13_1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"ClinicalTrials.gov.Identifier: NCT04982432 Orismilast for the treatment of mild to severe hidradenitis suppurativa (OSIRIS). Available from:https://clinicaltrials.gov/ct2/show/NCT04982432?id=NCT04982432&draw=2&rank=1&load=cart","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1111/bjd.18979","key":"e_1_2_10_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":null,"key":"e_1_2_10_15_1","year":"2010","issue":"8","author":"Kurd SK","volume":"146","first-page":"891","unstructured":null,"article-title":"The risk of depression, anxiety, and suicidality in patients with psoriasis: a population‐based cohort study","journal-title":"Arch Dermatol","doi-asserted-by":null},{"DOI":"10.5114/ada.2018.75810","key":"e_1_2_10_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":"10.1159/000365390","key":"e_1_2_10_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":"10.1111/bjd.14164","key":"e_1_2_10_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":"10.1016/j.jaad.2015.03.049","key":"e_1_2_10_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":"10.1096/fj.202001016RR","key":"e_1_2_10_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":"10.2147/CCID.S266036","key":"e_1_2_10_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":"10.1378/chest.12-2332","key":"e_1_2_10_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":"10.1016/j.jaad.2018.06.056","key":"e_1_2_10_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"}],"short-title":[],"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"update-policy":"https://doi.org/10.1002/crossmark_policy","alternative-id":["10.1111/jdv.18812"],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"published-print":{"date-parts":[[2023,4]]},"reference-count":22,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2023,1,18]]},"references-count":22,"short-container-title":["Acad Dermatol Venereol"],"is-referenced-by-count":21},"unpaywall":{"doi":"10.1111/jdv.18812","is_oa":true,"title":"Oral orismilast: Efficacy and safety in moderate‐to‐severe psoriasis and development of modified release tablets","updated":"2025-09-06T02:51:56+00:00","published_date":"2022-12-07","best_oa_location":{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.18812","pmh_id":null,"url_for_pdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.18812","url_for_landing_page":"https://doi.org/10.1111/jdv.18812"}}},"created_at":"2025-09-22T07:56:22.026Z","updated_at":"2025-09-22T14:20:55.574Z","tags":[{"paper_doi":"10.1111/jdv.18812","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"condition","value":"Plaque Psoriasis","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"generic","value":"orismilast","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"modality","value":"PDE4 Inhibitor","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"sample_size","value":"n=36","value_numeric":36},{"paper_doi":"10.1111/jdv.18812","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"warning","value":"Placebo denominator for PGA success was 17 due to missing data.","value_numeric":null},{"paper_doi":"10.1111/jdv.18812","tag_type":"warning","value":"This article reports both a phase 2a RCT and a separate phase 1 trial; design classification reflects the RCT but includes open-label PK components.","value_numeric":null}],"summaries":{"what_studied":"A phase 2a randomized, double-blind, placebo-controlled trial tested oral orismilast immediate-release 30 mg twice daily for 16 weeks in adults with moderate-to-severe plaque psoriasis (n=36). A single-site phase 1 study in healthy adults compared modified-release (MR) vs immediate-release (IR) pharmacokinetics, food effects, and short-term safety (single-dose parts; multiple-dose MR up to 60 mg twice daily for 17 days vs placebo).","key_result":"At week 16, mean PASI was 7.1 with orismilast vs 13.1 with placebo (LS mean difference −6.0; p=0.005); PASI-75 occurred in 8/18 (44.4%) vs 1/18 (5.6%), PGA success 7/18 (38.9%) vs 1/17 (5.6%), and DLQI improved by −9.1 vs placebo (3.8 vs 12.9; p=0.008). GI adverse events were frequent with IR (16/18, 88.9%; nausea 11/18, 61.1%; diarrhoea 9/18, 50.0%), leading to withdrawals in 9/18 (50.0%); in phase 1, MR and IR had similar PK, and GI AEs were lower with MR vs IR after single 30 mg doses (16.7% vs 33.3%; nausea 0% vs 27.8%).","limitations":"Small, single-centre phase 2a trial with high discontinuation (55.6% in orismilast IR; 50.0% in placebo) and LOCF imputation may bias efficacy estimates. Phase 1 findings were in healthy volunteers with small cohorts and included open-label parts; multiple-dose MR safety was short (17 days).","practice_takeaway":"Orismilast IR improved psoriasis signs but caused frequent GI AEs and high dropout; further development shifts to an MR tablet that kept similar exposure with fewer GI AEs after single dosing. Until larger patient trials with MR are complete, use remains investigational."}}],"initialOffset":10,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"PDE4 Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"PDE4 Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"PDE4 Inhibitor"}}}]]

Papers