004 Does methotrexate affect treatment persistence or effectiveness of adalimumab for psoriasis? A trial emulation cohort study

Abstract It is unclear whether concomitant methotrexate enhances the effectiveness and/or persistence of adalimumab in treating psoriasis. The OPTIMAP study (Optimizing Adalimumab Treatment in Psoriasis with Concomitant Methotrexate), a randomized controlled trial testing adalimumab against adalimumab + methotrexate, could not adequately answer this question due to under-recruitment. The aim of the current study is to replicate key aspects of the OPTIMAP trial design in a cohort study to provide a more precise estimate for the effect of concomitant methotrexate on adalimumab persistence and effectiveness. We conducted a cohort study using the British Association of Dermatologists Biologics and Immunomodulators Register, a national pharmacovigilance registry for people on systemic treatments for psoriasis, between 2007 and 2021. We included participants ≥ 18 years old who had at least one record of a Psoriasis Area and Severity Index (PASI) ≥ 8 and were naïve to adalimumab. We used the same exclusion criteria as in the OPTIMAP study. Participants received either adalimumab (Humira®) in the comparison arm or adalimumab (Humira) in addition to methotrexate and folic acid, with dosage as determined by the clinician in the intervention arm from initiation at cohort entry, and were censored if they deviated from the treatment strategy. The primary outcome is in the difference in the survival function for adalimumab at 1 year. The secondary outcome was the difference in the proportion of patients achieving a 75% reduction in PASI (PASI 75) at 1 year. We used inverse probability treatment weighting to correct for known differences in participant characteristics precomparison. Missing outcomes were accounted for using inverse probability of censoring weighting. We fitted a flexible parametric survival model and a generalized linear model with an identity link for the primary and secondary outcomes, respectively. There were 219 and 1376 participants in the intervention and comparison arms, respectively. Drug survival for the monotherapy arm at 1 year was 77.5% [95% confidence interval (CI) 75.3–79.8], and for the intervention arm, it was 75.3% (95% CI 66.9–84.7), with a difference of −2.3% (95% CI −11.4 to 6.9). The risk difference for PASI 75 at 1 year was −10.7% (95% CI −29.3 to 8.0), with a PASI 75 rate of 43.5% for the intervention arm (95% CI 25.4–61.9) and 54.2% for the comparison arm (95% CI 49.6–58.7). We did not find any significant difference for the persistence and effectiveness of adalimumab in people with psoriasis on methotrexate vs. those who were not on methotrexate in this study. This result is in keeping with the reported first-year outcomes of OPTIMAP. Clinicians and patients should consider alternative strategies to improve treatment outcomes in people with severe psoriasis.