Efficacy and safety of mavrilimumab in Japanese subjects with rheumatoid arthritis: Findings from a Phase IIa study

Abstract

Objective. A phase IIa study investigated efficacy and safety/tolerability of ascending doses of mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor [GM-CSFR]α monoclonal antibody) in adult subjects with moderate to severe rheumatoid arthritis from Japan and Europe. Findings from the Japanese population are presented.

Methods. Fifty-one subjects received mavrilimumab (10–100 mg) or placebo subcutaneously every other week for 12 weeks, followed by a 12-week follow-up period. The primary endpoint was the proportion of subjects achieving a Disease Activity Score using 28 joints (DAS28)-C-reactive protein (CRP) response (decrease > 1.2 from baseline). Secondary endpoints included DAS28-CRP remission, Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR) response.

Results. By Week 12, more mavrilimumab- versus placebo-treated subjects achieved a DAS28-CRP response (50.0% vs. 23.5%, p = 0.081); a significant response was seen in the 30 mg and 100 mg dose groups (both 75.0% vs. 23.5%, p = 0.028). The 100 mg group also demonstrated statistically significant HAQ-DI and ACR20 responses at Week 12. Results were generally consistent between Japanese and European populations. Overall, adverse events (AEs) were mild to moderate in intensity with one serious AE of pneumonia, considered possibly treatment-related.

Conclusions. A rapid and clinically meaningful response was seen in subjects treated with GM-CSFRα blockade with mavrilimumab, supporting further investigation of mavrilimumab for the treatment of RA in Japanese subjects.

Keywords:

• Granulocyte-macrophage colony-stimulating factor
• Mavrilimumab
• Phase II
• Rheumatoid arthritis

Acknowledgements

This study was sponsored by MedImmune and in part by AstraZeneca K.K. Medical writing services were provided by Sarah Reynolds (BSc) from QXV Communications, Macclesfield, UK, funded by MedImmune.

The authors thank Ruth Pereira (PhD) for her critical review and valuable comments during the manuscript preparation.

The following EARTH study investigators participated in this study: Tsutomu Takeuchi, Ryutaro Matsumura, Hisaaki Miyahara, Eiichi Suematsu, Yoshiya Tanaka, Toshiaki Miyamoto, Toshihisa Kanamono, Kiyoshi Migita, Yukitaka Ueki, Kanjiro Yamanaka, Yoshinobu Koyama, Shigeto Touma, Kazunori Sugimoto, Takemasa Matsuda, Daisuke Goto, Yoshinobu Koyama, Yukitomo Urata, Hisato Ishikawa.

Conflict of interest

Tsutomu Takeuchi is an investigator on the EARTH study and has received service honoraria from Abbott Japan Co. Ltd, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Eisai Co. Ltd, Mitsubishi Tanabe Pharma Co. and Pfizer Japan Inc, and research grants from Abbott Japan Co. Ltd, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nippon Shinyaku Co. Ltd, Novo Nordisk Pharma Ltd, Otsuka Pharmaceutical Co. Ltd, Pfizer Japan Inc., Sanofi K.K., Santen Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd and Teijin Pharma Ltd. Yoshiya Tanaka is an investigator on the EARTH study and has received consulting and speaking fees, and/or honoraria from Mitsubishi-Tanabe Pharma Co, Abbott Japan Co. Ltd., Eisai Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., Santen Pharmaceutical Co. Ltd., Pfizer Japan Inc, Astellas Pharma Inc, Daiichi-Sankyo Co. Ltd, GlaxoSmithKline K.K., AstraZeneca, Otsuka Pharmaceutical Co. Ltd., Actelion Pharmaceuticals Japan Ltd, Eli Lilly Japan K.K., Nippon Kayaku Co. Ltd, UCB Japan Co. Ltd, Quintiles Transnational Japan Co. Ltd, Ono Pharmaceutical Co. Ltd., and Novartis Pharma K.K., and has received research grants from Bristol-Myers Squibb, MSD K.K., Chugai Pharmaceutical Co. Ltd, Mitsubishi-Tanabe Pharma Corporation, Astellas Pharma Inc, Abbott Japan Co. Ltd., Eisai Co. Ltd. and Janssen Pharmaceutical K.K. David Close, Alex Godwood, Chi-Yuan Wu, and Didier Saurigny are employees of MedImmune and own stocks/stock options in AstraZeneca.