Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheumatic drugs in active rheumatoid arthritis: A Japan phase 3 trial (HARUKA)

Abstract

Objectives: To determine long-term safety and efficacy of sarilumab as monotherapy or with non-methotrexate (MTX) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in Japanese patients with active rheumatoid arthritis (RA).

Methods: In this double-blind, randomized study (NCT02373202), patients received subcutaneous sarilumab 150 mg q2w (S150) or 200 mg q2w (S200) as monotherapy or with non-MTX csDMARDs for 52 weeks. The primary endpoint was safety.

Results: Sixty-one patients received monotherapy (S150, n = 30; S200, n = 31) and 30 received combination therapy (S150 + csDMARDs, n = 15; S200 + csDMARDs, n = 15). Rates of treatment-emergent adverse events (TEAEs) were 83.3%/90.3%/93.3%/86.7% for S150/S200/S150 + csDMARDs/S200 + csDMARDs, respectively. Nasopharyngitis and neutropenia were the most frequently reported TEAEs. One serious infection was reported in each monotherapy group and in the S200 + csDMARDs group. There were no cases of grade 4 neutropenia; no patients with grade 3 neutropenia experienced associated serious infection. Improvements in ACR20/50/70 response rates were generally similar between the two monotherapy groups and between the two combination groups; improvements in physical function (Health Assessment Questionnaire-Disability Index, HAQ-DI) and DAS28-CRP were observed at weeks 24 and 52 (all groups).

Conclusion: The safety profile of sarilumab was consistent with known class effects of interleukin-6 signaling blockade therapeutics. Sarilumab as mono- or combination therapy improved clinical signs/symptoms and physical function in Japanese RA patients.

Keywords:

• Rheumatoid arthritis
• sarilumab
• Japan
• phase III
• anti-IL-6 receptor

Acknowledgements

The authors would like to thank the study participants and study investigators. The authors thank Ms Mariko Sumi’s contribution as a biological statistician on this study. Medical writing assistance, under the direction of the authors, was provided by Annette Smith, PhD, of CMC AFFINITY, a division of Complete Medical Communications Ltd, Macclesfield, UK, and Claire Lavin, PhD, on behalf of CMC AFFINITY, funded by Sanofi and Asahi Kasei Pharma Corporation.

Conflict of interest

Hideto Kameda has received consulting fees, speaking fees, and/or honoraria from AbbVie G.K.; Asahi Kasei Pharma Corporation; Bristol-Myers Squibb; Chugai Pharmaceutical Co., Ltd.; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; Mitsubishi Tanabe Pharma; Novartis Pharma K.K.; and Sanofi K.K.; and has received research grants from AbbVie G.K.; Asahi Kasei Pharma Corporation; Astellas Pharma Inc.; Bristol-Myers Squibb; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd.; Mitsubishi Tanabe Pharma; Novartis Pharma K.K. and Sanofi K.K.

Kazuteru Wada, Yoshinori Takahashi, Owen Hagino, and Hubert van Hoogstraten are employees of Sanofi and may hold stock and/or stock options in the company.

Neil M. H. Graham is an employee of Regeneron and may hold stock and/or stock options in the company.

Yoshiya Tanaka has received speaking fees from Daiichi Sankyo, Inc.; Astellas Pharma Inc.; Pfizer Inc; Mitsubishi Tanabe Pharma; Bristol-Myers Squibb; Chugai Pharmaceutical Co., Ltd.; YL Biologics Ltd.; Eli Lilly and Company; Sanofi K.K.; Janssen Pharmaceutical K.K.; UCB Japan Co. Ltd.; and has received research grants from Mitsubishi Tanabe Pharma; Takeda Pharmaceutical Company; Bristol-Myers Squibb; Chugai Pharmaceutical Co., Ltd.; Astellas Pharma Inc.; AbbVie G.K.; MSD K.K.; Daiichi Sankyo, Inc.; Pfizer Inc; Kyowa Kirin, Inc.; Eisai Co., Ltd.; and Ono Pharmaceutical Co., Ltd.

Additional information

Funding

This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.