Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials

Abstract

Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.

Keywords:

• Clinical trial
• Etanercept
• Monotherapy
• Review
• Rheumatoid arthritis

Acknowledgments

The studies described herein were designed and funded by Wyeth which was acquired by Pfizer Inc in October 2009. The authors would like to thank the investigators and participants in these studies. Medical writing was provided by Patricia McChesney, PhD, CMPP, and Samantha Forester, PhD, CMPP, of the Engage Scientific Solutions (part of the Envision Pharma Group) and was funded by Pfizer Inc.

Conflict of interest

Tsutomu Takeuchi, MD, has received research grants to the affiliated institution from AbbVie G.K., Abbott Japan Co. Ltd., Asahi Kasei Pharma Corp., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corp., Pfizer Japan Inc., Sanofi K.K., Santen Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd.; consulting fees from AbbVie G.K., Asahi Kasei Pharma Corp., AstraZeneca K.K., Daiichi Sankyo Co. Ltd., Eli-Lilly Japan K.K., Mitsubishi Tanabe Pharma Corp., Novartis Pharma K.K.; has served on the speakers’ bureau of 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 Corp., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd.

Nobuyuki Miyasaka, MD, has received research grants from Abbott, Astellas Pharmaceutical, Banyu Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai Pharmaceutical, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical, and Teijin Pharmaceutical.

Shinichi Kawai, MD, has received research grants from Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi-Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co Ltd.; and speaking fees from Abbott Japan Co., Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi-Tanabe Pharma Co., Pfizer Japan Inc., and UCB Japan Co., Ltd.

Naonobu Sugiyama, MD, PhD, Hirotoshi Yuasa, Noriaki Yamashita, PhD, and Noriko Sugiyama are employees of Pfizer Japan, Inc.

Lorin Craig Wagerle, PhD, Bonnie Vlahos, MBA, BSN, RN, and Joseph Wajdula, PhD, are employees of Pfizer Inc.

Supplementary material available online

Supplementary Figures 1–6 and Tables 1–7.