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

Objectives: Evaluate longer-term safety and efficacy of RZB in patients with active PsA who experienced inadequate response or intolerance to 1 or 2 biologic therapies and/or to at least 1 csDMARD therapy.

Methods: KEEPsAKE 2 (NCT03671148) is an ongoing, phase 3, multicenter study that includes a screening period; a 24-week double-blinded, randomized, placebo-controlled, parallel-group period (period 1); and an open-label extension period (period 2). Eligible patients were ≥18 years of age with active PsA (symptom onset ≥6 months before screening, meeting Classification Criteria for PsA [CASPAR], and ≥5 tender and ≥5 swollen joints) and had inadequate response or intolerance to 1 or 2 biologic therapies (Bio-IR) and/or ≥1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR). Patients received RZB 150 mg or placebo (PBO) at weeks 0, 4, and 16 (1:1). The primary endpoint was the proportion of patients achieving 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. Efficacy and safety were analyzed in patients who received ≥1 dose of study drug through week 52. Mixed-effect model with repeated measures and nonresponder imputation methods were used to assess continuous and binary variables, respectively. Treatment-emergent adverse events (TEAEs) were summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [PY]).

Results: At week 24, 51,3% of RZB-treated (N=224) and 26.5% of PBO-treated (N=219) patients achieved ACR20. At week 52, 58.5% of patients who were randomized to RZB and 55.7% of patients who were randomized to PBO and then switched to RZB at week 24 achieved ACR20. In patients with ≥3% of body surface area affected at baseline, 55.0% of RZB-treated patients (N=123) and 10.2% of PBO-treated patients (N=119) achieved PASI 90 at week 24. At week 52, 64.2% of patients randomized to RZB and 59.7% of patients who were randomized to PBO and then switched to RZB at week 24 achieved PASI 90. For other efficacy measures, similar trends were observed. RZB was well tolerated through 52 weeks of treatment, and EAERs of adverse events were stable between weeks 24 and 52. At the week 52 data cutoff (19 April 2021), the total EAER of any TEAE in patients receiving RZB was 184.2/100 PY.

Conclusion: Continuous RZB treatment resulted in maintained efficacy responses with a consistent safety profile through 52 weeks of treatment in patients with active PsA who were Bio-IR and/or 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 and provided writing support for this abstract. Medical writing assistance, funded by AbbVie, was provided by Jay Parekh, PharmD, of JB Ashtin.

Disclosure of Interests: Andrew Ostor Speakers bureau: AbbVie, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Filip van den Bosch Speakers bureau: AbbVie, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Kim Papp Speakers bureau: AbbVie, Amgen, Astellas, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, Lilly, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB, Consultant of: AbbVie, Amgen, Astellas, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, Lilly, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB, Grant/research support from: AbbVie, Amgen, Astellas, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, Lilly, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB, CECILIA ASNAL Speakers bureau: AbbVie, Amgen, Genentech, Janssen, Lilly, Pfizer, Roche, and R-Pharm., Consultant of: AbbVie, Amgen, Genentech, Janssen, Lilly, Pfizer, Roche, and R-Pharm., Grant/research support from: AbbVie, Amgen, Genentech, Janssen, Lilly, Pfizer, Roche, and R-Pharm., Ricardo Blanco Speakers bureau: AbbVie, Bristol Myers Squibb, Janssen, Lilly, Merck, Pfizer, and Roche., Consultant of: AbbVie, Bristol Myers Squibb, Janssen, Lilly, Merck, Pfizer, and Roche., Grant/research support from: AbbVie, Merck, and Roche, Jacob Aelion Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Galapagos/Gilead, Genentech, GlaxoSmithKline, Lilly, Mallinckrodt, Nektar Therapeutics, Nichi-Iko, Novartis, Pfizer, Regeneron, Roche, Sanofi, Selecta Biosciences, and UCB., Wenjing Lu Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Zailong Wang 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., Byron Padilla Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Alan Kivitz Shareholder of: AbbVie, Boehringer Ingelheim, Celgene, Flexion, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB., Speakers bureau: AbbVie, Boehringer Ingelheim, Celgene, Flexion, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB., Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Flexion, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB.