Higher risk of hospitalized infection, cardiovascular disease, and fracture in patients with rheumatoid arthritis determined using the Japanese health insurance database

Abstract

Objective: To evaluate the risk of hospitalized infection (HI), cardiovascular disease (CVD), stroke, and fracture in rheumatoid arthritis (RA) patients compared with non-RA patients using the Japanese health insurance database.

Method: Among individuals aged ≥18 years, RA cases were defined to have one RA diagnostic code and receiving ≥1 disease-modifying antirheumatic drug between 2005 and 2013 (n = 6,712). Age-, sex-, calendar year of the observation start-, and observation length-matched non-RA cases were selected at 1:5 (n = 33,560). Hazard ratios (HRs) were calculated using the time-dependent Cox regression analysis.

Results: Median age of the patients was 52.0 years. The incidence rates of HI, CVD, and fracture in the RA group were 2.42/100 person-years (PY), 4.94/1,000 PY, and 10.59/1,000 PY. The crude incidence rate ratios (95% CI) (RA vs. non-RA) for HI, CVD, and fracture were 2.47 (2.20–2.77), 1.89 (1.49–2.41), and 3.35 (2.80–4.02). The adjusted HR (95% CI) (RA vs. non-RA) was significantly elevated (HI, 1.74 [1.52–1.99], CVD, 1.38 [1.04–1.85], and fracture, 1.88 (1.54–2.31)].

Conclusion: The relatively young RA population had significantly higher risks of these complications than the non-RA, indicating importance of prevention of them even at young ages in clinical settings.

Key Words:

• Cardiovascular disease
• epidemiology
• fracture
• infection
• rheumatoid arthritis
• stroke

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Acknowledgments

We appreciate Shigeo Kamitsuji (Stagen Co., Ltd.) for his contribution of the statistical analyses of JMDC claims data, Rie Nishikino, and Makiko Kaneko (JMDC) for providing the JMDC claims database.

Conflict of interests

Tokyo Women’s Medical University (TWMU), particularly the Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases, has received unrestricted research grants from Ayumi Pharmaceutical Co.; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd., Nippon Kayaku Co., Ltd.; Taisho Toyama Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Co.; and Teijin Pharma Ltd., with which TWMU paid the salaries of RS and MH. HK received research grants/support from Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Actelion Pharmaceuticals Japan Ltd., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie Inc., Japan Blood Products Organization, Eisai Co., Ltd., Pfizer Inc., Novartis Pharma K.K., Ayumi Pharmaceutical Co., and received honoraria (lecture fee) from Ono Pharmaceuticals Co., Ltd., Teijin Pharma Ltd., Bristol Myers Squibb. SK, RK, and NM have nothing to declare.

Additional information

Funding

This work was supported by a grant-in-aid from the Ministry of Health, Labour, and Welfare, Japan for the Study Group on the Standardization of Clinical Practice of Rheumatoid Arthritis in Japan, the Ministry of Health, Labour, and Welfare of Japan (H26-meneki-shitei-021 to NM, MH, and RS).