Trend of patient characteristics and its impact on the response to adalimumab in patients with rheumatoid arthritis: post hoc time-course analysis of an all-case PMS in Japan

Abstract

Objectives. To investigate the relationship between changes in patient characteristics over time and the effectiveness and safety of adalimumab in the treatment of rheumatoid arthritis (RA) in clinical practice.

Methods. Patients enrolled in the post-marketing registry study in Japan were divided into 5 subgroups based on the time adalimumab treatment was initiated. Demographic and baseline characteristics and responses to adalimumab were compared among the 5 subgroups to detect any time-course trend. Multiple logistic regression analysis was performed to identify characteristics that were significantly associated with the effectiveness or safety of adalimumab and to estimate response rates and the incidence of adverse drug reactions in individual subgroups.

Results. During the study period, patient characteristics changed significantly over time, in particular with regard to prior biologic use and concomitant methotrexate therapy. There was a significant trend toward higher response rates and lower incidence of infections and injection-site reactions in patients initiating adalimumab later in the study. Patient characteristics, such as concomitant methotrexate therapy and early stage RA, were significant predictors of the effectiveness and safety of adalimumab.

Conclusions. Patient characteristics have changed since adalimumab became available for the treatment of RA; several of these characteristics were significant predictors of adalimumab effectiveness and safety.

Keywords:

• Adalimumab
• Effectiveness
• Post-marketing surveillance
• Rheumatoid arthritis
• Safety

Acknowledgments

We would like to express sincere thanks to the practicing rheumatologists in Japan for their cooperation in the post-marketing registry study of adalimumab. Simone Boniface of inScience Communications, Springer Healthcare, provided assistance with English language editing and preparation of the manuscript for submission. This assistance was funded by AbbVie GK (Japan). Abbott Laboratories separated proprietary pharmaceutical business into AbbVie in January 2013. The design, study conduct, and financial support for this study were provided by AbbVie under the guidance of the Postmarketing Surveillance (PMS) Committee of the Japan College of Rheumatology (JCR). AbbVie participated in the interpretation of data, review, and approval of the manuscript.

Funding

The design, study conduct and financial support for this study were provided by AbbVie under the guidance of the JCR postmarketing surveillance sub-committee. AbbVie participated in the interpretation of data, review, and approval of the manuscript.

Conflicts of interest

Doctors H. Yamanaka, M. Harigai, N. Ishiguro, S. Inokuma, S. Takei, T. Takeuchi, Y. Tanaka, and T. Koike are members of the Postmarketing Surveillance (PMS) Committee of the Japan College of Rheumatology. It is the belief of the authors that this does not constitute a conflict of interest. The doctors participated in the review and analysis of the PMS data in their capacity as committee members. The financial relationships of the authors with manufacturers of biological products used in the management of RA are listed. H. Yamanaka has received speaking fees from AbbVie GK, AstraZeneca K.K., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Company Ltd., Teijin Pharma Limited, and UCB Japan Co. Ltd. M. Harigai has received research grants, speaking fees, or honoraria from AbbVie GK, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Santen Pharmaceutical, Takeda Pharmaceutical, UCB Japan, and Pfizer and has received consultant fees from AbbVie GK, Bristol-Myers Squibb, Chugai Pharmaceutical, and Janssen Pharmaceutical. N. Ishiguro has received speaking fees from Takeda Pharma, Mitsubishi Tanabe Pharma, Astellas Pharma, Chugai Pharma, AbbVie GK, Bristol-Myers Squibb, Eisai, Janssen Pharma, and Pfizer Japan. S. Inokuma, None. S. Takei has received research grants, consulting fees, and/or speaker's fees from Eisai, Chugai, Takeda, Bristol-Myers K.K., Teijin, Pfizer, Mylan, Mitsubishi Tanebe, Asahi Kasei, and Astellas. T. Takeuchi has received grants from AbbVie GK, Astellas Pharma, Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nippon Shinyaku Co., Ltd., Otsuka Pharmaceutical, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., speaking fees from AbbVie GK, Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., and consultant fees from AstraZeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K. Y. Tanaka has received consulting fees, speaking fees, and/or honoraria from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, 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., AbbVie GK, Eisai Co., Ltd., and Janssen Pharmaceutical K.K. H. Suzuki is a full-time employee of AbbVie GK. Y. Shinmura is a full-time employee of AbbVie GK. T. Koike has received consultancies, speaking fees, and honoraria from AbbVie GK, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Santen Pharmaceutical, Takeda Pharmaceutical, Teijin Pharmaceutical, and Pfizer.