Background: 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 drug survival analysis warrant the application of additional outcomes to fully capture the performance of a biologic.
Objectives: 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.
Methods: We comprehensively identified studies in PubMed, Embase, Scopus and ClinicalTrials.gov. We defined two outcomes: (i) 'persistence at optimal response' (POR) or 'clinical remission', and (ii) 'persistence at suboptimal response' (PSR) or 'low disease activity'. Outcomes were measured as the proportions of patients with continuous exposure to a biologic who achieved ≥ 90% or 100% improvement in Psoriasis Area and Severity Index at the end of the predefined 5-year follow-up period.
Results: Eleven publications, comprising 18 randomized controlled trials and 11 202 patients, met the inclusion criteria and were included in the network meta-analysis. In the ranking analysis, guselkumab exhibited the highest cumulative probability of POR (0.84), followed by ixekizumab (0.82) and risankizumab (0.76). Conversely, etanercept (0.42), brodalumab (0.36), apremilast (0.25) and placebo (0.026) showed the lowest cumulative probabilities of POR. For PSR, guselkumab (0.86), ixekizumab (0.75) and risankizumab (0.71) also ranked highest, while brodalumab (0.42), secukinumab (0.23), etanercept (0.19) and placebo (0.019) presented the lowest PSR probabilities.
Conclusions: The highest rates of persistence with clear or almost clear skin can be expected with guselkumab, ixekizumab and risankizumab compared with 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.
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