Background: RZB, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits the p19 subunit of the human cytokine IL-23, is being investigated as a treatment for PsA.

Objectives: To compare efficacy and safety of RZB vs. placebo (PBO) in patients with PsA who had an inadequate response or intolerance to conventional synthetic disease modifying antirheumatic drug (csDMARD-IR).

Methods: KEEPsAKE 1 (NCT03675308) is an ongoing, phase 3 study that includes a screening period; a 24-week double-blinded, placebo-controlled, parallel-group period (period 1); and an open-label extension period (period 2). Eligible patients aged ≥18 years with active PsA (symptom onset ≥6 months prior to screening, meeting the Classification Criteria for PsA [CASPAR], and ≥5 swollen and ≥5 tender joints) and who had an inadequate response or intolerance to ≥1 csDMARD-IR, were randomized 1:1 to receive RZB 150 mg or placebo (PBO) at weeks 0, 4, and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology (ACR20) response at week 24. Period 2 started at week 24, and patients were switched to receive open-label RZB 150 mg every 12 weeks through week 208. Mixed-effect model repeated measures and nonresponder imputation methods were used to assess continuous and binary variables, respectively. Efficacy and safety were analyzed in all patients who received ≥1 dose of study drug through week 52. Treatment-emergent adverse events (TEAE) were summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [PY]).

Results: At week 24, a greater proportion of RZB-treated (N=483) vs PBO-treated (N=481) patients achieved ACR20 (55.3% and 32.8%, respectively). At week 52, 70% of patients who were randomized to receive RZB and 63% of patients who were randomized to receive PBO and switch to RZB at week 24 achieved ACR20. In patients with ≥3% of body surface area affected at baseline, 52.7% of RZB-treated patients (N=273) and 9.9% of PBO-treated patients (N=272) achieved ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at week 24; 67.8% who were randomized to receive RZB and 59.9% who were randomized to receive PBO and switch to RZB at week 24 achieved PASI 90 at week 52. Similar results were observed for other efficacy measures. RZB was well tolerated through 52 weeks of treatment. EAERs of adverse events were stable between weeks 24 and 52. At the week 52 data cut-off (19 April 2021), the total EAER of any TEAE in patients receiving RZB was 143.1/100 PY.

Conclusion: Continuous RZB treatment provided durable efficacy and a consistent safety profile through 52 weeks of treatment in patients with active PsA who were csDMARD-IR.

Acknowledgements: AbbVie, Inc. participated in the study design; study research; collection, analysis, and interpretation of data. AbbVie funded the research for this study. Medical writing assistance, funded by AbbVie, was provided by Jay Parekh, PharmD, of JB Ashtin.

Disclosure of Interests: Lars Erik Kristensen Speakers bureau: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Biogen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, and UCB, Kim Papp Speakers bureau: AbbVie, Amgen, Arcutis, Astellas, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Incyte, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sandoz, Sanofi Genzyme, and UCB, Consultant of: AbbVie, Amgen, Arcutis, Astellas, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermavant, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, Gilead, Incyte, Janssen, LEO Pharma, Lilly, Meiji Seika Pharma, Merck, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB, Grant/research support from: AbbVie, Amgen, Arcutis, Astellas, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermavant, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, Gilead, Incyte, Janssen, LEO Pharma, Lilly, Merck, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Leslie McCasland Consultant of: Lilly, Douglas White Speakers bureau: AbbVie and Novartis, Consultant of: AbbVie and Novartis, Wenjing Lu Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ahmed M. Soliman Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ann Eldred Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Lisa Barcomb Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Frank Behrens Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and Sanofi, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and Sanofi, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and Sanofi