Effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate for patients with moderate-to-severe psoriasis: a cohort study from BADBIR
Authors: Alabas Oras A , Mason Kayleigh J , Yiu Zenas Z N , Hampton Philip J , Reynolds Nick J , Owen Caroline M , Bewley Anthony , Laws Philip M , Warren Richard B , Lunt Mark , Smith Catherine H , Grifﬁths Christopher E M ,   BADBIR Study Group, Barker Jonathan , Morrison Simon , Bewley Anthony , Evans Ian , Griffiths Christopher , Ahmed Shehnaz , Kirby Brian , Kleyn Elise , Laws Philip , Hampton Philip , Alabas Oras , McElhone Kathleen , Yiu Zenas , Mackenzie Teena , McPherson Tess , Murphy Ruth , Ormerod Anthony , Walton Shernaz , Reynolds Nick , Smith Catherine , Warren Richard , Weller Richard , Gupta Girish , Zietemann Vera 
Published: January 2023

Abstract

Background
Real-world data evaluating effectiveness and persistence of systemic therapies for patients with psoriasis are limited.
Objectives To determine the effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters (FAEs) and methotrexate in patients with moderate-to-severe psoriasis.

Methods
Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective, multicentre pharmacovigilance register of patients with moderate-to-severe psoriasis receiving biologic and/or conventional systemic therapies, were analysed. Eligible patients were ≥ 16 years of age receiving a first course of acitretin, ciclosporin, FAEs or methotrexate between 2007 and 2021 with ≥ 6 months’ follow-up. Effectiveness was defined as achieving absolute Psoriasis Area and Severity Index (aPASI) ≤ 2 reported ≥ 4 weeks after treatment start date until date of cessation. To identify baseline clinical variables associated with treatment effectiveness, we used multivariable logistic regression models estimating the adjusted odds ratio (aOR) of achieving aPASI ≤ 2. To describe drug persistence associated with ineffectiveness, occurrence of adverse events or other reasons for discontinuation, survival estimates with 95% confidence intervals (CIs) were obtained using a flexible parametric model. Results were obtained using multiple imputed data.

Results
In total, 5430 patients were included in the analysis. Overall, 1023 (19%) patients were receiving acitretin, 1401 (26%) patients were on ciclosporin, 347 (6%) patients were on FAEs, and 2659 (49%) patients were receiving methotrexate at registration. The proportion of patients who achieved aPASI ≤ 2 was lower for those treated with acitretin [n = 118 (21%)] compared with those receiving ciclosporin [n = 233 (34%)], FAEs [n = 43 (29%)] and methotrexate [n = 372 (32%)]. Factors associated with ineffectiveness included prior experience to previous nonbiologic systemic therapies (acitretin) (aOR 0.64, 95% CI 0.42–0.96), male sex (methotrexate) (aOR 0.58, 95% CI 0.46–0.74), comorbidities (aOR 0.70, 95% CI 0.51–0.97) and alcohol consumption (≤ 14 units per week) (ciclosporin) (aOR 0.70, 95% CI 0.50–0.98). Persistence associated with all reasons for discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [survival estimate 46.1 (95% CI 44.0–48.3), 31.9 (95% CI 29.4–34.7), 30.0 (95% CI 27.5–32.4) and 35.0 (95% CI 29.9–40.9), respectively].

Conclusions
The real-world effectiveness and persistence of acitretin, ciclosporin, FAEs and methotrexate were generally low. Previous nonbiologic systemic therapies, male sex, comorbidities and alcohol consumption were risk factors associated with treatment ineffectiveness.