Biologic Disease-Modifying Anti-Rheumatic Drug Use and the Risk of Non-Vertebral Osteoporotic Fractures in Japanese Patients with Rheumatoid Arthritis: Results from the IORRA Cohort Study

Takefumi Furuya¹, Eisuke Inoue^1,2, Masanori Nakayama¹, Eiichi Tanaka¹, Katsunori Ikari¹, Ayako Nakajima³, Atsuo Taniguchi¹ and Hisashi Yamanaka¹, ¹Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, ²Center for Clinical Research and Development, National Center for Child Health and Development, Tokyo, Japan, ³Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Biologics, Fracture risk, Japanese, Osteoporosis and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 13, 2016

Title: Osteoporosis and Metabolic Bone Disease – Clinical Aspects and Pathogenesis - Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Previous U.S. and Canadian studies [1-3] have suggested that no significant associations exist between use of biologic disease-modifying anti-rheumatic drugs (DMARDs) and risk of non-vertebral fractures in patients with rheumatoid arthritis (RA), although previous small studies reported that biologic DMARDs preserve bone mineral density. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in Japanese patients with RA.

Methods:

The Institute of Rheumatology Rheumatoid Arthritis (IORRA) study, which began in 2000, was a prospective cohort study of Japanese patients with RA conducted at the Institute of Rheumatology, Tokyo Women’s Medical University (Tokyo, Japan). More than 116 publications have described various characteristics including fracture rate [4], fracture site, and risk factors for fractures [5] in Japanese patients with RA using this cohort. A nested case-control study was conducted using the IORRA cohort. RA subjects were followed from cohort entry until the earliest non-vertebral osteoporotic fracture at elbow, forearm, hip, humerus, pelvis, shoulder, and wrist. Controls were matched to cases (4:1 ratio) by age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥ 180 days pre-fracture (index). Conditional logistic regression was used to assess the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures.

Results:

Over the study period, 565 cases were identified (2,822 controls). The most common fracture sites were hip (25.3%), wrist (21.1%), and shoulder (15.2%). In total, 230 subjects (51 cases and 179 controls) were exposed to biologic DMARDs. The median duration of exposure was 2.5 (interquartile range [IQR], 1.0-4.0) and 2.5 (IQR, 1.0-4.5) years in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARD use and fracture risk (hazard ratio [HR] 1.11; 95% confidence interval [CI], 0.75-1.65) (Table). Baseline Japanese health assessment questionnaire disability index (JHAQ-DI), daily prednisone (PSL) dose, and bisphosphonate use were significantly (P < 0.001) associated with fracture risk.

Conclusion: Despite the positive impact of biologic DMARDs on bone remodeling observed in small studies, we were unable to demonstrate a reduction in the risk of non-vertebral osteoporotic fractures in Japanese patients with RA as reported in U.S. and Canadian patients with RA.

Table. Hazard ratios (95% confidence interval) of non-vertebral osteoporotic fractures in Japanese patients with RA: Multivariate analyses.

Factor

HR (95% CI)

RA disease duration

1.00 (0.99-1.01)

0.49

Body mass index

1.02 (0.99-1.05)

0.17

JHAQ-DI

1.59 (1.39-1.81)

< 0.001

NSAIDs use

1.06 (0.86-1.31)

0.56

Daily PSL dose, mg/day

1.06 (1.03-1.10)

< 0.001

Bisphosphonate use

1.51 (1.21-1.88)

< 0.001

Active vitamin D3 use

1.20 (0.92-1.58)

0.18

Proton pomp inhibitor use

0.76 (0.57-1.01)

0.059

Biologic DMARD use

1.11 (0.75-1.65)

0.59

References 1) Kawai VK, et al. Arthritis Care Res (Hoboken). 2013;65:1085-94; 2) Kim SY, et al. J Bone Miner Res. 2012;27:789-96; 3) Roussy JP, et al. Osteoporos Int. 2013;24:2483-92; 4) Ochi K, et al. Osteoporos Int. 2015;26:961-8; 5) Furuya T, et al. Osteoporos Int. 2013;24:1257-65.

Disclosure: T. Furuya, None; E. Inoue, None; M. Nakayama, None; E. Tanaka, Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Pfizer, Takeda Pharmaceutical, Daiichi Sankyo Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Nippon Kayaku, and Santen Pharmaceutical., 5; K. Ikari, AbbVie, Inc., Asahi Kasei Pharma Corp., Astellas Pharma Inc., Bristol-Myers Squibb Co., Chugai Pharmaceutical Co., Eisai Co., Ltd. Hisamitsu Pharmaceutical Co. Inc., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co.,, 2; A. Nakajima, None; A. Taniguchi, None; H. Yamanaka, Abbott, AbbVie, Asahikasei, Astellas, AstraZeneca, Bristol-Myers Squib, Chugai, Daiichi Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taishotoyama, Takeda, and Teijin; has received consulting fees from Abb, 2,Abbott, AbbVie, Astellas, Bristol-Myers Squib, Chugai, Eisai, Mitsubishi Tanabe, Pfizer, Takeda, and Teijin, 8.

To cite this abstract in AMA style:

Furuya T, Inoue E, Nakayama M, Tanaka E, Ikari K, Nakajima A, Taniguchi A, Yamanaka H. Biologic Disease-Modifying Anti-Rheumatic Drug Use and the Risk of Non-Vertebral Osteoporotic Fractures in Japanese Patients with Rheumatoid Arthritis: Results from the IORRA Cohort Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/biologic-disease-modifying-anti-rheumatic-drug-use-and-the-risk-of-non-vertebral-osteoporotic-fractures-in-japanese-patients-with-rheumatoid-arthritis-results-from-the-iorra-cohort-study/. Accessed .

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