Assessing the 5-year persistence in positive clinical response with innovative psoriasis treatments: a network meta-analysis of pasi score.

Abstract

Psoriasis is a chronic skin condition, for which the approval of several biologics has made a dramatic impact. Despite their initial treatment effectiveness, the challenge lies in understanding the long-term responses, as they may diminish over time. Limitations of the drug survival analysis warrant the application of additional outcomes to fully capture the performance of a biologic. We aimed to provide a broader perspective on the global landscape of biologic agents' persistence in positive clinical response by comparing innovative therapies over a 5-year period through a systematic review and network meta-analysis (NMA). We comprehensively identified studies in Pubmed, EMBASE, Scopus and clinicaltrial.gov. We defined two outcomes: 1) "persistence at optimal response" (POR) or "clinical remission", and 2) "persistence at suboptimal response" (PSR) or "low disease activity" as the proportion of patients with continuous exposition to a biologic who achieved a PASI 100 or PASI 90 responses, respectively, at the end of the predefined 5-year follow-up period. Eleven publications, comprising 18 RCTs and 11,202 patients met inclusion criteria and were included in the NMA. In the ranking analysis, guselkumab exhibited the highest cumulative (0.8397250), followed by ixekizumab (0.8185545), and risankizumab (0.7643864). Conversely, etanercept (0.4152295), brodalumab (0.3633977), apremilast (0.2452136), and placebo (0.0263) showed the lowest cumulative probability of POR. For PSR, guselkumab (0.86083636), ixekizumab (0.74931136), and risankizumab (0.71293182) also held the top ranks, while brodalumab (0.41740227), secukinumab (0.231575), etanercept (0.192775), and placebo (0.01934545) presented the lowest PSR probabilities. The highest rates of persistence with clear or almost clear skin can be expected with guselkumab, ixekizumab and risankizumab compared to other biologics. The proposed proxy definitions of long-term persistence (POR and PSR) are reliable measures of patients being successfully treated that warrant further exploration and validation.