Effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate for patients with moderate-to-severe psoriasis: a cohort study from BADBIR

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, multi-centre 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 stop date. 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 of discontinuation, survival estimates with 95% confidence interval (CI) were obtained using a flexible parametric model. Results were obtained using multiple imputed data. Results In total, 5430 patients were included in the analysis: 1023 (19%) on acitretin, 1401 (26%) ciclosporin, 347 (6%) FAEs and 2659 (49%) methotrexate at registration. The proportion of patients who achieved aPASI ≤ 2 was lower with acitretin 118 (21%) compared with those on ciclosporin 233 (34%), FAEs 43 (30%) and methotrexate 372 (32%). Factors associated with ineffectiveness included prior experience to previous non-biologic systemic therapies (acitretin) [(aOR, (95% CI) 0.64 (0.42, 0.96)], male sex (methotrexate) 0.58 (0.46, 0.74), co-morbidities 0.70 (0.51, 0.97) and alcohol consumption (≤14 units per week) (ciclosporin) 0.70 (0.50, 0.98). Persistence associated with all reasons of discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [(Survival estimate (95% CI), 46.1 (44.0, 48.3), 31.9 (29.4, 34.7), 30.0 (27.5, 32.4) and 35.0 (29.9, 40.9)], respectively. Conclusions The real-world effectiveness and persistence of acitretin, ciclosporin, FAEs and methotrexate were generally low. Previous non-biologic systemic therapies, male sex, comorbidities and alcohol consumption were risk factors associated with treatment ineffectiveness

Efficacy and safety of emerging immunotherapies in psoriasis.

Psoriasis is a common chronic inflammatory disease of the skin. Current biologic therapies are highly effective in the treatment of psoriasis, transforming the lives of patients with this significantly disabling disease. Advances in the understanding of the immunological pathogenesis of psoriasis have led to the development of new biologic therapies, targeting specific inflammatory cytokines upregulated in psoriasis. These include the IL-17 antagonists, secukinumab, brodalumab and ixekizumab; the IL-23 antagonists, guselkumab and tildrakizumab; and the oral small molecule therapies, tofacitinib and apremilast. Here, we review evidence for the efficacy and safety of these novel psoriasis therapies, providing clinicians with an overview of the next era in immunotherapy for psoriasis. </jats:p