Abstract

To evaluate the comparative effectiveness of anti-interleukin (IL)-23 agents (guselkumab, tildrakizumab, risankizumab) compared with other approved biologic therapies and apremilast in adults with moderate-to-severe plaque psoriasis. We systematically identified and reviewed data from Phase III randomized controlled trials (RCTs) of the three anti-IL-23 agents, anti-tumor necrosis factor-alpha (anti-TNF-α) agents (adalimumab, etanercept, infliximab, certolizumab pegol), anti-IL-17 agents (secukinumab, ixekizumab, brodalumab), ustekinumab, and apremilast in adults with moderate-to-severe plaque psoriasis. We performed a Bayesian network meta-analysis (NMA) adjusting for placebo response. Our outcome of interest was treatment response based on 50%, 75%, and 90% reduction in the Psoriasis Area and Severity Index (PASI 50/75/90). Forty-eight RCTs with a total of 25,260 patients were included in the NMA. Sixteen of the included trials examined head-to-head comparisons, five of which compared anti-IL-23 agents to anti-TNF-α agents or ustekinumab. NMA showed no statistical difference in achieving PASI 75 when two of the anti-IL-23 agents (guselkumab and risankizumab) were compared. However, both guselkumab and risankizumab were shown to be more effective in achieving PASI 75 than tildrakizumab (relative risk, RR=1.40, 95% credible interval, CrI: 1.24-1.64; RR=1.42, 95% CrI: 1.26-1.66, respectively). In addition, guselkumab and risankizumab were more effective than each anti-TNF-α agent (ranging from RRs of 1.10 for infliximab to 1.74 for etanercept), ustekinumab (RR=1.24, 95% CrI: 1.16-1.35; RR=1.26, 95% CrI: 1.18-1.37, respectively), and apremilast (RR=2.40, 95% CrI: 1.95-3.03; RR=2.44, 95% CrI: 1.98-3.12, respectively). Response based on PASI 75 did not statistically differ between either guselkumab or risankizumab and the anti-IL-17 agents. Similar findings were observed for PASI 50 and 90 outcomes. Based on clinical trial findings, guselkumab and risankizumab provide clinical benefit similar to that of anti-IL-17 agents and may provide incremental benefits in comparison to tildrakizumab, anti-TNF-α agents, ustekinumab, and apremilast.

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