Comparative Durability of Biologics for Patients With Moderate-to-Severe Psoriasis Adjusted for Drug Switching Over Time: 24-Month Outcomes From the International Observational Psoriasis Study of Health Outcomes (PSoHO)

Abstract

Introduction & Objectives Numerous biological therapies have become available in recent years for treating moderate-to-severe psoriasis (PsO). Studies providing real-world data directly comparing the effectiveness of these biologics are relatively scarce or limited by short observation periods. The Psoriasis Study of Health Outcomes (PSoHO) is a 36-month, non-interventional, international cohort study of patients (pts) with moderate-to-severe PsO, which enrolled 1981 pts ≥ 18 years of age from 23 countries, providing long-term data from a real-world setting needed for evidence-based care.

Materials & Methods The outcomes presented are the most contemporaneous prespecified endpoints: PASI100/90 durability, defined as individual pts achieving PASI100/90 at Week 12, and maintaining PASI100/90 at months 6, 12, 18, and 24. Adjusted odds ratios with 95% confidence intervals were generated using marginal structural models (MSM), which accounted for key confounders as well as treatment switching and discontinuation. Odds ratios are presented with non-responder imputation (NRI) and as observed (non-imputed) for ixekizumab (IXE) versus secukinumab (SEC), tildrakizumab (TILD), guselkumab (GUS), risankizumab (RIS), adalimumab (ADA), and ustekinumab (UST) for the overall population and a European Medicines Agency (EMA) on-label sub-population.

Results The adjusted analysis showed greater odds of durability response for IXE versus SEC, TILD, GUS, ADA, and UST, and similar odds to RIS for both the PASI90 and PASI100 durability outcomes in the overall population. The results of the EMA on-label sub-population analysis were similar, with the exception of the PASI100 durability outcome, where pts treated with IXE had significantly greater odds than those treated with RIS and were similar to those treated with SEC. Conclusion: Durability in the PSoHO study is based on rapid skin clearance and sustained therapeutic response, the primary treatment goals of many patients with PsO. It has previously been demonstrated that patients who achieve PASI100 earlier experience more days under a DLQI score of 0 or 1, emphasizing the correlation between the time taken to achieve total skin clearance and patients' quality of life. A limitation of long-term observational studies is potential bias caused by treatment switching, which can be impacted by study length, higher skin involvement, treatment costs, and access, but also by comorbid PsA, which approximately one-third of pts with PsO also suffer from. The MSM analysis was used to control for this bias. PSoHO provides real-world evidence that ixekizumab-treated pts show better PASI100/90 durability outcomes than those treated with adalimumab, ustekinumab, secukinumab, guselkumab, and tildrakizumab, while being similar to risankizumab in the overall population.