BERLIN – Prescribing hydroxychloroquine for the treatment of rheumatoid arthritis may reduce a patient’s risk of developing type 2 diabetes by more than 40%.
That’s the provocative implication of a longitudinal prospective observational study of 10,583 American patients with rheumatologist-diagnosed rheumatoid arthritis (RA) followed from 2000 through 2010. It’s a clinically important observation in light of the impact of diabetes on cardiovascular risk, Dr. Marie Holmqvist said at the annual European Congress of Rheumatology.
Findings from other, smaller studies also have shown the potential benefit of hydroxychloroquine in lowering the risk of diabetes in RA patients, but none was as large as this one (J. Clin. Rheumatol. 2011;17:115-20; JAMA 2007;298:187-93). The association has led some investigators to dub hydroxychloroquine "a diabetes drug in disguise" (BMJ Case Rep. 2009;2009. pii: bcr08.2008.0654).
At baseline, the patients with RA had an average age of 60 years and a mean 13.6-year disease duration. One-quarter of them were on hydroxychloroquine as mono- or combination therapy, 30% were on methotrexate with or without a tumor necrosis factor (TNF) inhibitor, and 42% were on other or no disease-modifying antirheumatic drugs (DMARDs).
During follow-up, 6.4% of subjects were diagnosed with new-onset type 2 diabetes. The incidence was 1.34 cases per 100 person-years. In a multivariate analysis adjusted for RA duration, ethnicity, body mass index, employment status, income, age, gender, comorbidity, and Health Assessment Questionnaire score, hydroxychloroquine use was independently associated with a 41% reduction in the likelihood of developing diabetes compared with Centers for Disease Control and Prevention–generated figures for the matched U.S. population.
Methotrexate with or without a TNF inhibitor was associated with a 20% decrease in the risk of diabetes as long as a patient wasn’t also on prednisone. If the methotrexate regimen included prednisone, the protective effect was lost. In contrast, hydroxychloroquine with prednisone remained protective, with an associated 40% risk reduction.
Prednisone by itself was associated with a 30% increased risk of developing diabetes. Most strikingly, golimumab (Simponi) was associated with a 12.3-fold increased risk. None of the other medications prescribed for RA showed a significant relationship with diabetes risk, reported Dr. Holmqvist of Karolinska University, Stockholm.
Her study was funded by the Karolinska Institute and the U.S. National Data Bank for Rheumatic Diseases. Dr. Holmqvist reported having no financial conflicts.