Comparative Effectiveness of Targeted Immunomodulators for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis.

BACKGROUND The comparative effectiveness of available targeted immunomodulators for moderate-to-severe psoriasis has not been evaluated. OBJECTIVE To evaluate the comparative effectiveness of targeted immunomodulators for adults with moderate-to-severe plaque psoriasis. METHODS Systematic literature review of placebo-controlled and head-to-head randomized trials of eight targeted immunomodulators that evaluated clinical benefits or harms. The primary outcome was a 75% improvement on the Psoriasis Area and Severity Index ("PASI 75"). We also conducted a network meta-analysis (NMA) adjusted for placebo response to perform indirect comparisons between agents. RESULTS In the NMA, the targeted immunomodulators ordered by an increasing relative risk (demonstrating greater likelihood) of achieving PASI 75 relative to placebo were: apremilast (6.2), etanercept (9.6), adalimumab (13.0), ustekinumab (14.0), secukinumab (15.4), infliximab (16.2), brodalumab (17.3), and ixekizumab (17.9). Ixekizumab, brodalumab, and infliximab were all statistically superior to ustekinumab, adalimumab, etanercept, and apremilast; results were similar to head-to-head studies where data were available. LIMITATIONS Much of the evidence is short-term (10-16 weeks); limited direct comparisons. CONCLUSIONS The Interleukin-17A inhibitors are more effective in achieving clearance than ustekinumab, which are, in turn, generally more effective than etanercept, adalimumab, and apremilast.