Journal of the European Academy of Dermatology and Venereology

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>There are limited data on the impact of the route of administration of methotrexate (MTX) on drug survival in psoriasis.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate the impact of the initial route of administration of MTX (monotherapy) on drug survival in patients with moderate to severe skin psoriasis.</jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p>A prospective cohort study based on the Psobioteq registry, included from July 2012 to January 2023, patients with plaque, erythrodermic or guttate psoriasis, naive to MTX, biologics and apremilast, who initiated MTX monotherapy. Factors associated with drug survival were identified using Kaplan–Meier curves and Cox regression analyses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, 406 patients were included, 58.1% received MTX per os (MTX‐PO) and 41.9% subcutaneously (MTX‐SC). At MTX initiation, the median PASI score was 11, and 67.3% had DLQI ≥6. Adjusted drug survival did not statistically differ according to the route of administration (<jats:italic>p</jats:italic> = 0.15).</jats:p></jats:sec><jats:sec><jats:title>Limitations</jats:title><jats:p>Limited number of patients leading to a potential lack of power. Residual confounding cannot be waived due to the observational nature of the data.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Overall MTX survival did not significantly differ according to the route of administration. However, with MTX‐SC, the hazard of discontinuation for ineffectiveness was lower and of discontinuation for intolerance was higher than with MTX‐PO.</jats:p></jats:sec>

publication_history

received

accepted

published

Agence Nationale de Sécurité du Médicament et des Produits de Santé

AbbVie

Pfizer

Ministère de la Santé

Janssen Pharmaceutica

Amgen

Novartis

Celgene

LEO Pharma Research Foundation

Eli Lilly and Company

Merck

Psoriasis

Lancet

French guidelines on the use of systemic treatments for moderate‐to‐severe psoriasis in adults

J Eur Acad Dermatol Venereol

Effectiveness of subcutaneous methotrexate in chronic plaque psoriasis

J Drugs Dermatol

The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis

Ann Rheum Dis

Drug survival and predictor factors for discontinuation of methotrexate in psoriasis: a real‐life multicenter study

Int J Dermatol

Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six‐month, multicenter, randomized, double‐blind, controlled, phase IV trial

Arthritis Rheum

Comparison of overall efficacy and safety of oral versus subcutaneous methotrexate in severe psoriasis

Dermatol Ther

Comparison of the clinical efficacy of subcutaneous vs. oral administration of methotrexate in patients with psoriasis vulgaris: a randomized controlled trial

Clin Exp Dermatol

Systemic methotrexate therapy for psoriasis: past, present and future

There are limited data on the impact of the route of administration of methotrexate (MTX) on drug survival in psoriasis.
To evaluate the impact of the initial route of administration of MTX (monotherapy) on drug survival in patients with moderate to severe skin psoriasis.
A prospective cohort study based on the Psobioteq registry, included from July 2012 to January 2023, patients with plaque, erythrodermic or guttate psoriasis, naive to MTX, biologics and apremilast, who initiated MTX monotherapy. Factors associated with drug survival were identified using Kaplan-Meier curves and Cox regression analyses.
In total, 406 patients were included, 58.1% received MTX per os (MTX-PO) and 41.9% subcutaneously (MTX-SC). At MTX initiation, the median PASI score was 11, and 67.3% had DLQI ≥6. Adjusted drug survival did not statistically differ according to the route of administration (p = 0.15).
Limited number of patients leading to a potential lack of power. Residual confounding cannot be waived due to the observational nature of the data.
Overall MTX survival did not significantly differ according to the route of administration. However, with MTX-SC, the hazard of discontinuation for ineffectiveness was lower and of discontinuation for intolerance was higher than with MTX-PO.

Impact of methotrexate administration route on drug survival in psoriasis: Results from PSOBIOTEQ.

Impact of methotrexate administration route on drug survival in psoriasis: Results from <scp>PSOBIOTEQ</scp>

Photodermatology, Photoimmunology &amp; Photomedicine

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Several widely used drugs have photosensitizing properties, and much research has been conducted to find associations between their use and the risk of developing cutaneous malignant melanoma (cM), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC), often with conflicting results.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess whether the use of commonly prescribed photosensitizing drugs increases skin cancer risk.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Analyses were performed using a large cohort of women, with prospectively collected information on phenotypic traits and sun exposure. Comprehensive information on pharmaceutical treatments and skin cancer occurrence was obtained through national registries. Drugs with photosensitizing properties were grouped according to the Anatomical Therapeutic Chemical system in nine groups, and associations between the use of such drugs were investigated using multivariable Cox regression analysis. The number of retrieved daily doses was analyzed to test the dose–response relationship.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Hormone replacement therapy significantly increased the risk of BCC (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 1.11–1.39), cSCC (HR 1.23; 95% CI: 1.03–1.47) and cM (HR 1.31; 95% CI: 1.01–1.69), with estrogen driving this risk. There was a trend of increased risk of BCC and cM with higher doses of estrogen treatment. Subgroup analysis among those using diuretics showed that loop diuretics were associated with increased cSCC risk (HR 1.6; 95% CI: 1.3–2.0), including a positive association between risk and dose. Furthermore, increased risks of BCC (HR 1.25; 95% CI: 1.09–1.44) and cM (HR 1.41; 95% CI: 1.03–1.93) were associated with thiazide use. NSAIDs showed a possible curvilinear association to BCC and cSCC.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Estrogen treatment increased the risk of all investigated skin cancers. Among those using diuretics, loop diuretics increased the risk of cSCC, and thiazide use increased the risk of BCC. We suggest that physicians should advise female patients prescribed estrogen, thiazides, or loop diuretics to limit their sun exposure.</jats:p></jats:sec>

Cancerfonden

HudFonden

Participation in a Prospective Cohort Study on Melanoma Did Not Affect the Incidence and Mortality of the Studied Disease

Acta Dermato‐Venereologica

Hormonal and Reproductive Factors and Incidence of Basal Cell Carcinoma and Squamous Cell Carcinoma in a Large, Prospective Cohort

Journal of the American Academy of Dermatology

Several widely used drugs have photosensitizing properties, and much research has been conducted to find associations between their use and the risk of developing cutaneous malignant melanoma (cM), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC), often with conflicting results.
To assess whether the use of commonly prescribed photosensitizing drugs increases skin cancer risk.
Analyses were performed using a large cohort of women, with prospectively collected information on phenotypic traits and sun exposure. Comprehensive information on pharmaceutical treatments and skin cancer occurrence was obtained through national registries. Drugs with photosensitizing properties were grouped according to the Anatomical Therapeutic Chemical system in nine groups, and associations between the use of such drugs were investigated using multivariable Cox regression analysis. The number of retrieved daily doses was analyzed to test the dose-response relationship.
Hormone replacement therapy significantly increased the risk of BCC (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 1.11-1.39), cSCC (HR 1.23; 95% CI: 1.03-1.47) and cM (HR 1.31; 95% CI: 1.01-1.69), with estrogen driving this risk. There was a trend of increased risk of BCC and cM with higher doses of estrogen treatment. Subgroup analysis among those using diuretics showed that loop diuretics were associated with increased cSCC risk (HR 1.6; 95% CI: 1.3-2.0), including a positive association between risk and dose. Furthermore, increased risks of BCC (HR 1.25; 95% CI: 1.09-1.44) and cM (HR 1.41; 95% CI: 1.03-1.93) were associated with thiazide use. NSAIDs showed a possible curvilinear association to BCC and cSCC.
Estrogen treatment increased the risk of all investigated skin cancers. Among those using diuretics, loop diuretics increased the risk of cSCC, and thiazide use increased the risk of BCC. We suggest that physicians should advise female patients prescribed estrogen, thiazides, or loop diuretics to limit their sun exposure.

Photosensitizing Drugs and Risk of Skin Cancer in Women-A Prospective Population-Based Study.

Photosensitizing Drugs and Risk of Skin Cancer in Women—A Prospective Population‐Based Study

JAMA Dermatology

<jats:sec id="ab-doi240027-4"><jats:title>Importance</jats:title><jats:p>Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice.</jats:p></jats:sec><jats:sec id="ab-doi240027-5"><jats:title>Objective</jats:title><jats:p>To evaluate clinical effectiveness and reasons for discontinuation of dupilumab treatment in children, adults, and older adults with AD with up to 5 years of treatment in daily practice.</jats:p></jats:sec><jats:sec id="ab-doi240027-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This prospective multicenter cohort study was conducted using the BioDay registry (4 academic and 10 nonacademic hospitals in the Netherlands) to identify patients with AD of all ages who were treated with dupilumab between October 2017 and December 2022.</jats:p></jats:sec><jats:sec id="ab-doi240027-7"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numeric rating scale (NRS) for pruritus, stratified by children (&amp;amp;lt;18 years), adults (18-64 years), and older adults (≥65 years). In addition, time to response, treatment responders, EASI subscores, second treatment episodes, and thymus- and activation-related chemokine and eosinophil levels were assessed. For patients who discontinued dupilumab, the reason for discontinuation was evaluated.</jats:p></jats:sec><jats:sec id="ab-doi240027-8"><jats:title>Results</jats:title><jats:p>In total, 1286 patients with AD (median [IQR] age, 38 [26-54] years; 726 [56.6%] male) were treated with dupilumab,  including 130 children, 1025 adults, and 131 older adults. The median (IQR) follow-up time was 87.5 (32.0-157.0) weeks. Most patients maintained controlled AD, with EASI of 7 or lower and NRS for pruritus of 4 or lower varying between 78.6% and 92.3% and 72.2% and 88.2% for up to 5 years of treatment, respectively, while up to 70.5% of all patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks. Mean EASI and NRS for pruritus were 2.7 (95% CI, 1.2-4.2) and 3.5 (95% CI, 2.7-4.3), respectively, after 5 years of treatment. Statistically significant differences between age groups were found over time for EASI and IGA; however, differences were rather small (week 52: EASI, 0.3-1.6; IGA, 0.12-0.26). No statistically significant differences between age groups were found for NRS for pruritus. Median thymus- and activation-related chemokine levels considerably decreased from 1751 pg/mL (95% CI, 1614-1900 pg/mL) to 390 pg/mL (95% CI, 368-413 pg/mL) after 6 months of treatment and remained low. Median eosinophil levels temporarily increased up to week 16, with a subsequently statistically significant decrease over time. In total, 306 patients (23.8%) discontinued dupilumab after a median (IQR) of 54.0 (29.0-110.00) weeks, with adverse events among 98 patients (7.6%) and ineffectiveness among 85 patients (6.6%) as the most frequently reported reasons. Forty-one patients (3.2%) restarted dupilumab, and most of these patients recaptured response.</jats:p></jats:sec><jats:sec id="ab-doi240027-9"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this cohort study with up to 5 years of follow-up, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered to a dosing interval of every 3 or 4 weeks. Treatment was discontinued in 23.8% of patients mainly due to adverse events and/or ineffectiveness.</jats:p></jats:sec>

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-week results from the Dutch BioDay registry.

J Am Acad Dermatol

Dupilumab maintains long-term disease control in adults with moderate-to-severe atopic dermatitis as measured by well-controlled weeks: results from the LIBERTY AD CHRONOS clinical trial.

Dermatol Ther (Heidelb)

Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study.

A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: ineffectiveness in head-and-neck dermatitis.

Longer dupilumab dosing intervals in adult patients with atopic dermatitis: experience from a French multicentre retrospective cohort study.

Br J Dermatol

Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis.

Allergy

Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: a retrospective analysis.

Successful tapering of dupilumab in patients with atopic dermatitis with low disease activity: a large pragmatic daily practice study from the BioDay registry.

Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial.

JAMA Dermatol

Two-year efficacy, safety, and drug survival of dupilumab for atopic dermatitis: a real-world Canadian multicenter retrospective study.

JAAD Int

104-week safety and effectiveness of dupilumab in the treatment of severe atopic dermatitis: the experience of 5 reference dermatology units in Spain.

An Bras Dermatol

Dupilumab for the treatment of atopic dermatitis: real-world data from the Czech Republic BIOREP registry.

J Dermatolog Treat

Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an open-label study of adults with moderate-to-severe atopic dermatitis.

Am J Clin Dermatol

What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study.

A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: many options, no standards.

Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus.

Acta Derm Venereol

Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies.

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management.

Expert Rev Respir Med

Biomarkers for atopic dermatitis: a systematic review and meta-analysis.

Curr Opin Allergy Clin Immunol

Real-life effectiveness and safety of dupilumab in adolescents with atopic dermatitis: a 52-week single-center retrospective study.

Dupilumab improves clinical scores in children and adolescents with moderate to severe atopic dermatitis: a real-world, single-center study.

J Allergy Clin Immunol Pract

A 52-week update of a multicentre Italian real-world experience on effectiveness and safety of dupilumab in adolescents with moderate-to-severe atopic dermatitis.

Effect of dupilumab on blood eosinophil counts in patients with asthma, chronic rhinosinusitis with nasal polyps, atopic dermatitis, or eosinophilic esophagitis.

Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study.

Dupilumab with topical corticosteroids provides rapid and sustained improvement in adults with moderate-to-severe atopic dermatitis across anatomic regions over 52 weeks.

Dupilumab demonstrates rapid and consistent improvement in extent and signs of atopic dermatitis across all anatomical regions in pediatric patients 6 years of age and older.

Facial and neck erythema associated with dupilumab treatment: a systematic review.

Reasons for discontinuation of dupilumab in adult atopic dermatitis in clinical practice.

Evaluation of long-term efficacy, safety, and reasons for discontinuation of dupilumab for moderate to severe atopic dermatitis in clinical practice: a retrospective cohort study.

Long-term drug survival of dupilumab and associated predictors in moderate-to-severe atopic dermatitis: a real-world prospective cohort study.

Global, regional, and national cancer incidence and death for 29 cancer groups in 2019 and trends analysis of the global cancer burden, 1990-2019.

J Hematol Oncol

Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice.
To evaluate clinical effectiveness and reasons for discontinuation of dupilumab treatment in children, adults, and older adults with AD with up to 5 years of treatment in daily practice.
This prospective multicenter cohort study was conducted using the BioDay registry (4 academic and 10 nonacademic hospitals in the Netherlands) to identify patients with AD of all ages who were treated with dupilumab between October 2017 and December 2022.
Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numeric rating scale (NRS) for pruritus, stratified by children (<18 years), adults (18-64 years), and older adults (≥65 years). In addition, time to response, treatment responders, EASI subscores, second treatment episodes, and thymus- and activation-related chemokine and eosinophil levels were assessed. For patients who discontinued dupilumab, the reason for discontinuation was evaluated.
In total, 1286 patients with AD (median [IQR] age, 38 [26-54] years; 726 [56.6%] male) were treated with dupilumab, including 130 children, 1025 adults, and 131 older adults. The median (IQR) follow-up time was 87.5 (32.0-157.0) weeks. Most patients maintained controlled AD, with EASI of 7 or lower and NRS for pruritus of 4 or lower varying between 78.6% and 92.3% and 72.2% and 88.2% for up to 5 years of treatment, respectively, while up to 70.5% of all patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks. Mean EASI and NRS for pruritus were 2.7 (95% CI, 1.2-4.2) and 3.5 (95% CI, 2.7-4.3), respectively, after 5 years of treatment. Statistically significant differences between age groups were found over time for EASI and IGA; however, differences were rather small (week 52: EASI, 0.3-1.6; IGA, 0.12-0.26). No statistically significant differences between age groups were found for NRS for pruritus. Median thymus- and activation-related chemokine levels considerably decreased from 1751 pg/mL (95% CI, 1614-1900 pg/mL) to 390 pg/mL (95% CI, 368-413 pg/mL) after 6 months of treatment and remained low. Median eosinophil levels temporarily increased up to week 16, with a subsequently statistically significant decrease over time. In total, 306 patients (23.8%) discontinued dupilumab after a median (IQR) of 54.0 (29.0-110.00) weeks, with adverse events among 98 patients (7.6%) and ineffectiveness among 85 patients (6.6%) as the most frequently reported reasons. Forty-one patients (3.2%) restarted dupilumab, and most of these patients recaptured response.
In this cohort study with up to 5 years of follow-up, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered to a dosing interval of every 3 or 4 weeks. Treatment was discontinued in 23.8% of patients mainly due to adverse events and/or ineffectiveness.

Long-Term Effectiveness and Reasons for Discontinuation of Dupilumab in Patients With Atopic Dermatitis.

Long-Term Effectiveness and Reasons for Discontinuation of Dupilumab in Patients With Atopic Dermatitis

<jats:sec id="ab-doi230059-4"><jats:title>Importance</jats:title><jats:p>Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.</jats:p></jats:sec><jats:sec id="ab-doi230059-5"><jats:title>Objective</jats:title><jats:p>To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.</jats:p></jats:sec><jats:sec id="ab-doi230059-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.</jats:p></jats:sec><jats:sec id="ab-doi230059-7"><jats:title>Exposures</jats:title><jats:p>Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.</jats:p></jats:sec><jats:sec id="ab-doi230059-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score–weighted Cox proportional hazards regression models.</jats:p></jats:sec><jats:sec id="ab-doi230059-9"><jats:title>Results</jats:title><jats:p>Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).</jats:p></jats:sec><jats:sec id="ab-doi230059-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.</jats:p></jats:sec>

Psoriasis: classical vs. paradoxical: the yin-yang of TNF and type I interferon.

Front Immunol

Biologic agent–associated cutaneous adverse events: a single center experience.

Clin Med Res

Eczematous eruption during anti-interleukin 17 treatment of psoriasis: an emerging condition.

Disease concomitance in psoriasis.

Mutual antagonism of T cells causing psoriasis and atopic eczema.

N Engl J Med

Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.

Am J Hum Genet

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

Nat Genet

Can atopic eczema and psoriasis coexist? a systematic review and meta-analysis.

Skin Health Dis

Psoriasiform dermatitis during dupilumab treatment for moderate-to-severe atopic dermatitis in children.

Pediatr Dermatol

Review of dupilumab-associated inflammatory arthritis: an approach to clinical analysis and management.

JAAD Case Rep

The British Association of Dermatologists’ Biologic Interventions Register (BADBIR): design, methodology and objectives.

Risk of serious infection in patients with psoriasis receiving biologic therapies: a prospective cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

J Invest Dermatol

Regression models and life-tables.

J R Stat Soc B

An introduction to propensity score methods for reducing the effects of confounding in observational studies.

Multivariate Behav Res

The central role of the propensity score in observational studies for causal effects.

Biometrika

Variable selection for propensity score models.

Am J Epidemiol

Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls.

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: results from a 52-week, open-label, phase 3 study (UNCOVER-J).

J Dermatol

Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis.

Efficacy and safety of secukinumab in elderly subjects with moderate to severe plaque psoriasis: a pooled analysis of phase III studies.

Drugs Aging

Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study.

Eczema as an adverse effect of anti-TNFa therapy in psoriasis and other Th1-mediated diseases: a review.

Concurrence of psoriasis vulgaris and atopic eczema in a single patient exhibiting different expression patterns of psoriatic autoantigens in the lesional skin.

Mixed profile of cytokines in paradoxical eczematous eruptions associated with anti-IL-17 therapy.

Integrated safety analysis of treatment-emergent eczematous reactions in patients with moderate-to-severe psoriasis treated with ixekizumab, etanercept and ustekinumab.

Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy.

Clin Gastroenterol Hepatol

Predictive factors of eczema-like eruptions among patients without cutaneous psoriasis receiving infliximab: a cohort study of 92 patients.

Dermatology

Atopic polygenic risk score is associated with paradoxical eczema developing in psoriasis patients treated with biologics.

Filaggrin mutations, atopic eczema, hay fever, and asthma in children.

J Allergy Clin Immunol

Prevalence and characteristics of atopic dermatitis among young adult females and males—report from the Swedish population-based study BAMSE.

Effects of cyclosporine A on T cell development and clonal deletion.

Science

Inhibitory effects of cyclosporine on human regulatory T cells in vitro.

Transplant Proc

Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.
To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.
This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.
Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.
Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models.
Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).
In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis.

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis

Papers