Effectiveness and survival of methotrexate versus adalimumab in patients with moderate-to-severe psoriasis: a cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)
Authors: Alabas Oras A , Mason Kayleigh J , Yiu Zenas Z N , Warren Richard B , Lunt Mark , Smith Catherine H , Grifﬁths Christopher E M ,   the 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: May 2023

Abstract

Background
Most information on the comparative effectiveness and survival of methotrexate (MTX) and adalimumab (ADA) in the treatment of psoriasis is from randomized control trials and may not translate to the everyday clinical setting.

Objectives
To determine the real-world effectiveness and survival of MTX and ADA in patients with moderate-to-severe psoriasis registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).

Methods
Eligible patients were registered in BADBIR, ≥ 16 years of age and receiving a first course of MTX or ADA between September 2007 and December 2021, with ≥ 6 months of follow-up. Effectiveness was defined as achieving an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 reported ≥ 13 weeks after the treatment start date until the stop date. The average treatment effect (ATE) was estimated using inverse probability of treatment weighting with propensity score, including baseline covariates. ATE results were presented as risk ratios (RR). A flexible parametric model was used to estimate adjusted standardized average survival, defined as treatment discontinuation associated with ineffectiveness or the occurrence of adverse events (AEs) at 6, 12 and 24 months. Restricted mean survival time (RMST) at 2 years of treatment exposure was calculated.

Results
In total, 6575 patients (median age 44 years; 44% female) were analysed; 2659 (40.4%) were prescribed MTX and 3916 (59.5%) ADA. The proportion of patients achieving PASI ≤ 2 was higher in the ADA cohort (77.4%) than in the MTX cohort (37.4%). ADA was more effective than MTX [RR 2.20, 95% confidence interval (CI) 1.98–2.45]. Overall survival associated with ineffectiveness or AEs was lower in the MTX cohort than in the ADA cohort at 6 months [survival estimate 69.7 (95% CI 67.9–71.5) vs. 90.6 (95% CI 89.8–91.4)], 1 year [survival estimate 52.5 (95% CI 50.4–54.8) vs. 80.6 (95% CI 79.5–81.8)] and 2 years [survival estimate 34.8 (95% CI 32.5–37.2) vs. 68.6 (95% CI 67.2–70.0)]. The difference in RMST (years) overall, or when stratified by ineffectiveness and AEs, was 0.53 (95% CI 0.49–0.58), 0.37 (95% CI 0.33–0.42) and 0.29 (95% CI 0.25–0.33), respectively.

Conclusions
Patients on ADA were twice as likely to be clear or nearly clear of psoriasis and were less likely to discontinue their medication than patients on MTX. Findings from this real-world cohort provide important information to aid clinicians managing patients with psoriasis.