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FRI0252 Summary of neutropenia in patients with rheumatoid arthritis treated with sirukumab in the sirround phase 3 clinical trials
  1. T Takeuchi1,
  2. Y Tanaka2,
  3. M Schiff3,
  4. M Harigai4,
  5. K Brown5,
  6. R Rao6,
  7. K Fei7,
  8. S Popik7,
  9. K Yoshizawa8,
  10. Q Wang7,
  11. B Hsu7
  1. 1Division of Rheumatology, Keio University School of Medicine, Tokyo
  2. 2University of Occupational and Environmental Health, Kitakyushu, Japan
  3. 3University of Colorado School of Medicine, Denver, CO, United States
  4. 4Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
  5. 5GlaxoSmithKline, Collegeville, PA, United States
  6. 6GSK Medicines Research Centre, Hertfordshire, United Kingdom
  7. 7Janssen Research & Development, LLC, Spring House, PA, United States
  8. 8Janssen Pharm KK Japan, Chiyoda-ku, Tokyo, Japan

Abstract

Background Neutropenia has been reported with interleukin-6 (IL-6) pathway inhibitors and could potentially be associated with increased rates of infection. The reduced neutrophil counts seen with IL-6 inhibitors may be due to effects on margination of circulating neutrophils as opposed to a decrease in bone marrow production or reduced survival. Efficacy of sirukumab (SIR), a human anti-IL-6 cytokine monoclonal antibody, has recently been shown in several phase 3 trials.

Objectives To assess incidence of neutropenia from completed and ongoing SIRROUND clinical studies.

Methods Neutrophil counts were compared for SIR 50mg q4w and 100mg q2w doses vs placebo (pbo) in the pbo-controlled period (Wks 0–18) of 2 phase 3 trials and in long-term analysis for the 5-trial, phase 3 program.

Results 2926 pts received SIR for up to 3.4y with a median duration of 1.46y. For the 18-wk pbo-controlled period, neutropenia was more frequent in both SIR groups compared with pbo. Across all groups, the majority of the decreases in neutrophil counts were National Cancer Institute Common Terminology Criteria for Adverse Events grade 0/1, within the normal range, and the incidence of grade 3/4 decreases was low across groups (Table). Neutropenia began at Wk 2 and persisted through the study period. In long-term analysis, the proportions of pts with grade 1, 2, or 3 neutropenia were slightly higher than in the 18-wk pbo-controlled period, suggesting the majority of events occurred early. No dose relationship was observed in the grade or frequency of neutropenia. Grade 3/4 neutropenia was mostly transient and resolved after interrupting the dose or resolved within the dosing interval such that no change in dose schedule was required. The majority of grade 4 decreases in neutrophils were not correlated with infections; 2 cases of serious infections occurred with grade 4 neutropenia. The distribution of neutropenia by grade was similar in pts who did or did not use disease-modifying antirheumatic drugs (DMARDs) at baseline.

Table 1.

Neutropenia by Maximum Toxicity Grade Across Phase 3 Trials (n, %)

Conclusions Across phase 3 studies, there was no dose effect of SIR on neutropenia, and the use of DMARDs did not have an apparent effect on neutropenia. The majority of grade 4 neutropenia with SIR was not associated with infections.

Disclosure of Interest 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, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., and SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol-Myers K.K., and 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., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Daiichi Sankyo Co., Ltd., Celtrion, and Nipponkayaku Co. Ltd., Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, and Eisai, Speakers bureau: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, and GlaxoSmithKline, M. Schiff Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, UCB, Speakers bureau: AbbVie, M. Harigai Grant/research support from: AbbVie Japan, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Ono Pharmaceuticals, Santen Pharmaceutical, Takeda Pharmaceutical, UCB Japan, Teijin Pharma, Consultant for: AbbVie Japan, Janssen Pharma, Chugai Pharmaceutical, Teijin Pharma, Eli Lilly Japan, and Zenyaku Kogyo, K. Brown Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, R. Rao Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, S. Popik Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, K. Yoshizawa Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Q. Wang 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

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