Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: Postmarketing surveillance report of 7740 patients

Abstract

Objectives. To confirm the safety and effectiveness of adalimumab and to evaluate the influence of the concomitant use of methotrexate (MTX).

Methods. Postmarketing surveillance of 7740 Japanese rheumatoid arthritis (RA) patients was performed. All patients who received adalimumab in the registration period were followed for 28 weeks after starting treatment for safety and 24 weeks for effectiveness. Effectiveness was measured by duration of morning stiffness, swollen and tender joint counts (28 joints), patient global assessment of disease activity, erythrocyte sedimentation rate and serum C-reactive protein.

Results. Comparable rates of adverse drug reactions (ADRs) were reported in this study and in the interim analysis. Age, pulmonary disease history or comorbidity, co-existing diabetes mellitus, concomitant MTX at doses of > 8 mg/week and concomitant glucocorticoids at doses of > 5 mg/day were risk factors for infections. All mean values of effectiveness measurements improved. Relatively lower disease activity at baseline, biologic-naïve, concomitant MTX use and early RA stage/low functional class were background factors contributing to the effectiveness. The combination of adalimumab with MTX improved the response to adalimumab treatment.

Conclusion. Adalimumab, especially with concomitant use of MTX, provided significant improvement in disease activity, without any unexpected ADRs in Japanese RA patients.

Keywords:

• Adalimumab
• Effectiveness
• Postmarketing surveillance
• Rheumatoid arthritis
• Safety

Acknowledgement

We thank Noriko Takahashi of Springer Japan K.K., Springer Healthcare Business Unit, who provided medical writing support. Abbott Laboratories separated proprietary pharmaceutical business into AbbVie in January 2013.

Funding

The design, study conduct and financial support for this study was 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.

Conflict of interest

Doctors T. Koike, M. Harigai, N. Ishiguro, S. Inokuma, S. Takei, T. Takeuchi, H. Yamanaka and Y. Tanaka 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 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. T. Koike has received consultancies, speaking fees and honoraria from Abbott, Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Santen Pharmaceutical, Takeda Pharmaceutical, Teijin Pharmaceutical and Pfizer. M. Harigai has received research grants, speaking fees and honoraria from Abbott Japan, 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 received consultant fees from Abbott Japan, Bristol Myers Squibb, Chugai Pharmaceutical and Janssen Pharmaceutical. N. Ishiguro has received speaking fees from Takeda Pharma, Mitsubishi Tanabe Pharma, Astellas Pharma, Chugai Pharma, Abbott Japan, 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 KK, Teijin, Pfizer, Mylan, Mitsubishi Tanebe, Asahi Kasei and Astellas. T. Takeuchi has received grants from Abbott Japan Co., Ltd., 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 Abbott Japan Co., Ltd., 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 Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co. and Asahi Kasei Medical K.K. H. Yamanaka has received speaking fees from Abbott Japan Co., Ltd, 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. S. Haruna is a full-time employee of AbbVie GK. N. Ushida is a full-time employee of AbbVie GK. K. Kawana is a full-time employee of AbbVie GK. Y. Tanaka, has received consulting fees, speaking fees and/or honoraria from Mitsubishi-Tanabe Pharma Corporation, 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., Astra-Zeneca, 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.

Notice of correction

The original Early Online version of this article contained a typographical error in Table 3. The row opposite Pneumonia should have aligned with “n” This has been corrected in the current article.