Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

Abstract

Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate.

Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate.

Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules.

Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules.

Keywords:

• Certolizumab pegol
• Clinical study
• Rheumatoid arthritis
• TNFα
• TNF inhibitor

Acknowledgements

This manuscript was funded by UCB. The authors acknowledge Tadao Okamoto, PhD, UCB, Tokyo, Japan, for publication management and Taku Kambayashi, MD, PhD, for editorial services. The authors also acknowledge all investigators from the J-RAPID OLE study: Hokkaido University Hospital (T. Atsumi), Hokkaido Medical Center for Rheumatic Diseases (K. Tanimura), Tomakomai City Hospital (A. Fujisaku), Oki Medical Clinic (I. Oki), Tohoku Kosei Nenkin Hospital (T. Kodera), East-Sendai Rheumatism and Internal Medicine Clinic (T. Izumiyama), Taga General Hospital (S. Ota), Inoue Hospital (H. Inoue), Saitama Medical Center (K. Amano), Jichi Medical University Hospital (T. Yoshio), Tsukuba University Hospital (T. Sumida), Chiba University Hospital (N. Watanabe), Yonemoto Orthopedic Clinic (K. Yonemoto), The University of Tokyo Hospital (K. Kawahata), Tokyo Medical and Dental University Hospital Faculty of Medicine (H. Kohsaka), Institute of Rheumatology Tokyo Women's Medical University (H. Yamanaka), Keio University Hospital (M. Kuwana), Jikei University Hospital (D. Kurosaka), Juntendo University Hospital (Y. Takasaki), Showa University Hospital (T. Kasama), Toho University Ohashi Medical Center (T. Ogawa), Kyorin University Hospital (Y. Arimura), Fukuhara Hospital (A. Yamaguchi), Tokyo Metropolitan Bokutoh Hospital (M. Nagashima), Tokyo Metropolitan Ohtsuka Hospital (T. Yamada), Yokohama Rosai Hospital (Y. Kita), Tokai University Hospital (Y. Suzuki), Kitasato University Hospital (S. Hirohata), Sagamihara Hospital (T. Matsui), Gunma University Hospital (Y. Nojima), Nagano Red Cross Hospital (T. Kanamono), Nagoya University Hospital (T. Kojima), Nagoya Medical Center (A. Kaneko), Kondo Orthopedic and Rheumatology Clinic (K. Kondo), Ito Orthopedic Clinic (T. Ito), Nagoya City University Hospital (Y. Hayami), Niigata University Medical and Dental Hospital (M. Nakano), Niigata Rheumatic Center (A. Murasawa), Saiseikai Takaoka Hospital (S. Honjo), Osaka Minami Medical Center (Y. Saeki), Matsubara Mayflower Hospital (T. Matsubara), Okayama University Hospital (H. Wakabayashi), Higashi-Hiroshima Memorial Hospital (S. Yamana), Kurashiki Medical Clinic (Y. Yoshinaga), Hiroshima Clinic (K. Amano), Sanin Rosai Hospital (H. Kishimoto), Kagawa University Hospital (H. Dobashi), Tokushima University Hospital (J. Kishi), Matsuyama Red Cross Hospital (S. Mizuki), University of Occupational and Environmental Health, Hospital (Y. Tanaka), Kitakyushu Municipal Medical Center (H. Nishizaka), Kyushu Medical Center (H. Miyahara), Shono Rheumatism Clinic (E. Shono), Kondo Rheumatology and Orthopedic Clinic (M. Kondo), Kurume University Medical Center (T. Fukuda), St. Mary's Hospital (T. Nakano), Nagasaki University Hospital of Medicine and Dentistry (A. Kawakami), Nagasaki Medical Center (K. Migita), Sasebo Chuo Hospital (Y. Ueki), Nagasaki Medical Hospital of Rheumatology (M. Tsuboi), Nagasaki Atomic Bomb Hospital (M. Nakashima), Oribe Clinic of Rheumatism and Medicine (M. Oribe), Kumamoto Saishunso National Hospital (S. Mori), Kumamoto Orthopaedic Hospital (M. Sakaguchi), Shimin-No-Mori Hospital (T. Hidaka) and Kagoshima Red Cross Hospital (T. Matsuda).

Conflict of interest

The competing interests of all authors are provided below.

• Y. Tanaka has received research funding from BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbvie and Daiichi- Sankyo and has served on speaker bureaus for UCB, Mitsubishi- Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD and Asahi Kasei.

• K. Yamamoto has served as a consultant for UCB, Pfizer, Abbott, BMS, Roche, Chugai, Mitsubishi-Tanabe and Eisai and has received research funding from UCB, Pfizer, Abbott, Santen, Mitsubishi-Tanabe and Eisai.

• T. Takeuchi has served as a consultant for AstraZeneca, Eli Lilly, Novartis, Mitsubishi-Tanabe and Asahi Kasei; has received research support from Abbott, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi-Aventis, Santen, Takeda and Teijin; and has served on speaker bureaus for Abbott, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda.

• H. Yamanaka has served as a consultant for, and received research funding from, UCB, Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda.

• N. Ishiguro has received research funding from Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken and Pfizer and has served on speaker bureaus for Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken, Pfizer, Taisho-Toyama and Otsuka.

• K. Eguchi has served as a consultant for UCB.

• A. Watanabe has received research support from Daiichi- Sankyo, Kyorin, Shionogi, Taisho, Dainippon-Sumitomo, Taiho, Toyama Chemical and Meiji Seika and has served on speaker bureaus for MSD, GSK, Shionogi, Daiichi-Sankyo, Taisho-Toyama, Dainippon-Sumitomo, Mitsubishi-Tanabe and Pfizer.

• H. Origasa has served as a consultant for UCB and Astellas.

• T. Shoji is an employee of UCB.

• N. Miyasaka has received research support from Pfizer, Takeda, Mitsubishi-Tanabe, Chugai, Abbott, Eisai and Astellas.

• T. Koike has served on speaker bureaus for UCB, Pfizer, Chugai, Abbott, Mitsubishi-Tanabe, Takeda, Eisai, Santen, Astellas, Taisho-Toyama, BMS, Teijin and Daiichi-Sankyo.