Hydroxychloroquine and Risk of Diabetes in Patients With Rheumatoid Arthritis

Wasko, Mary Chester M. MD, MSc
Hubert, Helen B. MPH, PhD
Lingala, Vijaya Bharathi PhD
Elliott, Jennifer R. MD
Luggen, Michael E. MD
Fries, James F. MD
Ward, Michael M. MD, MPH

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania (Drs Wasko and Elliott); Stanford University Medical Center, Palo Alto, California (Drs Hubert, Lingala, and Fries); Division of Immunology, University of Cincinnati, Cincinnati, Ohio (Dr Luggen); and Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland (Dr Ward).

Corresponding Author: Mary Chester M. Wasko, MD, MSc, University of Pittsburgh, 3500 Terrace St, BST 704 S, Pittsburgh, PA 15261 ([email protected]).

Author Contributions: Dr Wasko had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Wasko, Hubert, Elliott, Fries, Ward.

Acquisition of data: Wasko, Hubert, Lingala, Luggen, Fries.

Analysis and interpretation of data: Wasko, Hubert, Lingala, Fries, Ward.

Drafting of the manuscript: Wasko, Hubert, Elliott.

Critical revision of the manuscript for important intellectual content: Wasko, Hubert, Lingala, Elliott, Luggen, Fries, Ward.

Statistical analysis: Hubert, Lingala, Ward.

Obtained funding: Wasko, Fries, Ward.

Administrative, technical, or material support: Elliott, Fries.

Study supervision: Wasko, Hubert, Fries, Ward.

Financial Disclosures: Dr Wasko reported being a consultant to Centocor in cardiovascular outcomes in ongoing rheumatoid arthritis clinical trials and has been a coinvestigator in a Merck-sponsored study of thromboembolic markers in rheumatoid arthritis and osteoarthritis. Dr Wasko reported receiving contractual reimbursement as site principal investigator for an Aventis-sponsored clinical trial of leflunomide in rheumatoid arthritis, ending in November 2002. Dr Wasko reported receiving contractual reimbursement as site principal investigator for rheumatoid arthritis clinical trials sponsored by Centocor, Roche, Human Genome Sciences, and Novartis. No other authors reported disclosures.

Funding/Support: This study was conducted with support from the Arthritis Foundation of Western Pennsylvania, the National Arthritis Foundation, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health.

Role of the Sponsor: Neither the Arthritis Foundation nor the National Institutes of Health was involved in the design and conduct of the study or in the collection, management, analysis, or interpretation of the data, or the preparation, review, or approval of the manuscript.

Additional Contributions: The authors dedicate this article to the memory of John Sibley, MD, professor of medicine, Royal University Hospital, Saskatoon, Saskatchewan, whose contributions over his 15 years as an ARAMIS investigator were essential to numerous publications based on the ARAMIS cohort prior to his untimely death in 2007. Janice Sabatine, PhD, paid consultant, provided administrative and editorial contributions to the preparation of the manuscript.

JAMA: The Journal of the American Medical Association 298(2):p 187-193, July 11, 2007.

Context

Hydroxychloroquine, a commonly used antirheumatic medication, has hypoglycemic effects and may reduce the risk of diabetes mellitus.

Objective

To determine the association between hydroxychloroquine use and the incidence of self-reported diabetes in a cohort of patients with rheumatoid arthritis.

Design, Setting, and Patients

A prospective, multicenter observational study of 4905 adults with rheumatoid arthritis (1808 had taken hydroxychloroquine and 3097 had never taken hydroxychloroquine) and no diagnosis or treatment for diabetes in outpatient university-based and community-based rheumatology practices with 21.5 years of follow-up (January 1983 through July 2004).

Main Outcome Measures

Diabetes by self-report of diagnosis or hypoglycemic medication use.

Results

During the observation period, incident diabetes was reported by 54 patients who had taken hydroxychloroquine and by 171 patients who had never taken hydroxychloroquine, with incidence rates of 5.2 per 1000 patient-years of observation compared with 8.9 per 1000 patient-years of observation, respectively (P < .001). In time-varying multivariable analysis with adjustments for possible confounding factors, the hazard ratio for incident diabetes among patients who had taken hydroxychloroquine was 0.62 (95% confidence interval, 0.42–0.92) compared with those who had not taken hydroxychloroquine. In Poisson regression, the risk of incident diabetes was significantly reduced with increased duration of hydroxychloroquine use (P < .001 for trend); among those taking hydroxychloroquine for more than 4 years (n = 384), the adjusted relative risk of developing diabetes was 0.23 (95% confidence interval, 0.11–0.50; P < .001), compared with those who had not taken hydroxychloroquine.

Conclusion

Among patients with rheumatoid arthritis, use of hydroxychloroquine is associated with a reduced risk of diabetes.