Background: The efficacy of guselkumab (GUS), an interleukin (IL)-23 p19-subunit inhibitor, has been demonstrated for psoriatic arthritis (PsA) in two pivotal phase 3 trials (DISCOVER‑1&2). A third phase 3b trial (COSMOS) evaluated GUS in patients with PsA who had an inadequate response (IR) to tumor necrosis factor inhibitors (TNFi). GUS has previously been compared to targeted PsA therapies through network meta-analysis (NMA).

Objectives: This NMA update was to include data for GUS in TNFi-IR patients from COSMOS, as well as two additional key comparators, risankizumab (RIS), an IL-23 inhibitor, and upadacitinib (UPA), a Janus kinase inhibitor (JAKi).

Methods: A systematic literature review identified PsA randomized controlled trials up to February 2021. A subsequent hand-search identified data for newer agents, including congresses up to July 2021. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs). Analyses used fixed or random effects models and adjusted for placebo response via meta-regression on baseline risk when feasible. Multinomial models were used for ACR and PASI. Results were summarized by ranking treatments in league tables according to results derived from NMAs. Conclusions (ie, comparable or better/worse) for GUS 100 mg every 8/4 weeks (Q8W/Q4W) versus comparators were based on overlap of pairwise 95% credible intervals (CrIs) (ie, treatments are comparable if CrIs overlap 1 [dichotomous outcomes] or 0 [continuous outcomes]).

Results: Thirty-three phase 3 studies were included in the NMAs. Studies were placebo-controlled up to 24 weeks except for 2 head-to-head studies, and evaluated 15 targeted PsA therapies in TNFi naïve, IR, or mixed populations. For ACR 20 response, GUS Q8W and Q4W ranked 14th and 12th among 23 treatments and were comparable to most other active agents, including RIS and UPA, subcutaneous (SC) TNFi, and most IL-17A inhibitors (IL-17Ai), as demonstrated by overlap in pairwise 95% CrIs with unity. Results were similar for ACR 50 and 70 responses. For PASI 90, GUS Q8W and Q4W ranked 2nd and 1st among 23 treatments and were better than multiple agents, including all SC TNFi, JAKi, including UPA, and other small molecules, as demonstrated by nonoverlap in pairwise 95% Crls with unity. GUS Q8W and Q4W were similar to RIS and most IL-17Ai for PASI 90, but point estimates consistently favored GUS. For vdH-S score, GUS Q8W and Q4W ranked 8th and 3rd among 18 treatments; GUS Q4W was better than RIS, and both GUS Q8W and Q4W were comparable to most other agents, including UPA. SAEs were comparable across most agents.

Conclusion: GUS demonstrated better skin efficacy than most other targeted PsA therapies, including UPA. For vdH-S, both GUS dose regimens were comparable to most treatments, with both GUS dose regimens ranking higher than most, including UPA and RIS. Both GUS dose regimens demonstrated ACR responses that were comparable to most other agents, including UPA and RIS, and ranked favorably in the network for SAEs.

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Disclosure of Interests: Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB Pharma, Lai-Shan Tam Grant/research support from: Novartis and Pfizer, Raji Rajalingam Employee of: EVERSANA, Steve Peterson Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Global Services, LLC, Fareen Hassan Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen EMEA, Soumya D Chakravarty Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Christine CONTRE Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, France, Alison Armstrong Employee of: EVERSANA, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Leo, Novartis, and UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Leo, Novartis, and UCB Pharma, Grant/research support from: Pfizer, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen and UCB Pharma