SAT0166 An Analysis of Laboratory Results from 2 Randomized, Double-Blind Studies of Sirukumab in Patients with Active Rheumatoid Arthritis Refractory To Disease-Modifying Anti-Rheumatic Drug Treatment: Table 1

Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese studies. In these 2 Phase 3 studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC