OP0307 Efficacy and safety of risankizumab, a selective il-23p19 inhibitor, in patients with active psoriatic arthritis over 24 weeks: results from a phase 2 trial

Background Interleukin-23 (IL-23), a key regulator of multiple effector cytokines, has been implicated in the pathogenesis of psoriatic lesions, synovitis, enthesitis, and bone erosion. Risankizumab (RZB) is a humanised IgG1 monoclonal antibody that binds to p19 subunit of IL-23, selectively inhibiting this critical cytokine. Objectives To report the efficacy and safety of different doses of RZB in patients (pts) with active psoriatic arthritis (PsA) over 24 weeks. Methods In this double-blind, parallel-design, dose-ranging Phase 2 study, pts with active PsA (stratified by prior TNFi use and concurrent MTX use) were randomised in a 2:2:2:1:2 ratio to receive RZB (150 mg at weeks [Wks] 0, 4, 8, 12, and 16 [Arm 1], 150 mg at Wks 0, 4, and 16 [Arm 2], 150 mg at Wks 0 and 12 [Arm 3], 75 mg single dose at Wk 0 [Arm 4]) or matching placebo (PBO, Arm 5). Pts completing Wk 24 visit had an option to enter a separate open-label extension (OLE) study; pts not entering the OLE were followed until Wk 32. Efficacy assessments included ACR20/50/70, PASI, minimal disease activity (MDA), DAS28(CRP), dactylitis count, SPARCC enthesitis index, pain-VAS, HAQ-DI, and mTSS scores. Results Of the 185 pts who received the study drug, 173 (93.5%) completed 16 Wks of treatment and 145 (78.4%) entered OLE at Wk 24. The primary endpoint of ACR20 response at Wk 16 was achieved by pts in each of the RZB arms. 1 At Wk 24, ACR20/50/70 responses were significantly higher in pts receiving RZB (pooled across all RZB arms) compared with PBO (table 1). PASI75/90/100 responses at Wk 24 were significantly higher in RZB-treated pts compared with PBO. At Wk 24, RZB-treated pts achieved significantly higher MDA responses as well as greater improvements in DAS28(CRP) and Pain–VAS. Improvements in HAQ-DI and enthesitis from BL were numerically greater in RZB arms. At Wk 24, RZB-treated pts (pooled across all RZB arms) showed significant improvement from BL in mTSS compared with PBO. Treatment-emergent adverse events (TEAEs), collected up to Wk 32, were comparable across treatment arms (table 2); the most common TEAE was infection. There were no deaths or cases of tuberculosis in RZB-treated pts; 2 adjudicated major adverse cardiovascular events were reported in RZB arms. Conclusions Pts with active PsA treated with RZB maintained improvement in joint and skin symptoms through 24 wks. RZB-treated pts (pooled across all RZB arms) showed evidence for inhibition of radiographic progression. RZB was well-tolerated with no new or unexpected safety findings. Reference [1] Mease PJ, et al. Arthritis Rheumatol 2017;69(suppl 10). Acknowledgements AbbVie and Boehringer Ingelheim (BI) funded the study (NCT02719171); BI contributed to its design and participated in data collection and both participated in data analysis and interpretation of the data, and in writing, review, and approval of the publication. AbbVie, BI, and the authors thank all study investigators for their contributions and the patients who participated in this study. Statistical support: Andrew Topp; medical writing: Deepa Venkitaramani, PhD, both of Abbvie. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol Myers, Celgene, Genentech, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB, Consultant for: AbbVie, Amgen, Bristol Myers, Celgene, Genentech, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB, Speakers bureau: AbbVie, Amgen, Bristol Myers, Celgene, Genentech, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB, H. Kellner Grant/research support from: AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB, A. Morita Grant/research support from: AbbVie, Eli Lilly Japan K.K., Janssen Pharmaceutical K. K., Kyowa Hakko Kirin Co., Ltd, Leo Pharma, Maruho Co, Ltd, Mitsubishi-Tanabe Pharma, and Novartis, Consultant for: AbbVie, Eli Lilly Japan K.K., Janssen Pharmaceutical K. K., Kyowa Hakko Kirin Co., Ltd, Leo Pharma, Maruho Co, Ltd, Mitsubishi-Tanabe Pharma, and Novartis, Speakers bureau: AbbVie, Eli Lilly Japan K.K., Janssen Pharmaceutical K. K., Kyowa Hakko Kirin Co., Ltd, Leo Pharma, Maruho Co, Ltd, Mitsubishi-Tanabe Pharma, and Novartis, A. Kivitz Grant/research support from: AbbVie, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Horizon, Janssen, Merck, Novartis, Pfizer, Sanofi, Sun Pharma Advanced Research, Regeneron, and UCB, Consultant for: AbbVie, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Horizon, Janssen, Merck, Novartis, Pfizer, Sanofi, Sun Pharma Advanced Research, Regeneron, and UCB, Speakers bureau: AbbVie, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Horizon, Janssen, Merck, Novartis, Pfizer, Sanofi, Sun Pharma Advanced Research, Regeneron, and UCB, K. Papp Grant/research support from: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp and Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Consultant for: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp and Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Speakers bureau: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp and Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, S. Aslanyan Employee of: Boehringer Ingelheim, B. Berner Employee of: Boehringer Ingelheim, S. Chen Shareholder of: AbbVie, Employee of: AbbVie, A. Eldred Shareholder of: AbbVie, Employee of: AbbVie, F. Behrens Grant/research support from: AbbVie, Amgen, Celgene, Chugai, Eli Lilly, Genzyme Janssen, Novartis, Pfizer, Roche, Sandoz, and Sanofi, Consultant for: AbbVie, Amgen, Celgene, Chugai, Eli Lilly, Genzyme Janssen, Novartis, Pfizer, Roche, Sandoz, and Sanofi, Speakers bureau: AbbVie, Amgen, Celgene, Chugai, Eli Lilly, Genzyme Janssen, Novartis, Pfizer, Roche, Sandoz, and Sanofi