DMARDs May Modify Diabetes Risk in RA or Psoriasis Patients

Laurie Barclay, MD

June 22, 2011

June 22, 2011 — Use of disease-modifying antirheumatic drugs (DMARDs) may modify diabetes (DM) risk in patients with rheumatoid arthritis (RA) or psoriasis, according to the results of a retrospective cohort study reported in the June 21 issue of the Journal of the American Medical Association.

"...RA and psoriasis have been linked with insulin resistance and ...DM," write Daniel H. Solomon, MD, MPH, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues. "Prior investigations suggest that systemic immunosuppressive drugs may improve insulin resistance and reduce the risk of DM."

The goal of the study was to compare the risk for newly recorded DM associated with use of a variety of DMARDs among 121,280 participants with a diagnosis of either RA or psoriasis documented on at least 2 visits. During a mean follow-up period of 5.8 months, administrative data were analyzed from patients enrolled in 2 large health insurance programs: 1 in Canada and 1 in the United States.

Four mutually exclusive drug regimens were defined: (1) tumor necrosis factor (TNF) inhibitors with or without other DMARDs; (2) methotrexate without TNF inhibitors or hydroxychloroquine; (3) hydroxychloroquine without TNF inhibitors or methotrexate; and (4) other nonbiologic DMARDs without TNF inhibitors, methotrexate, or hydroxychloroquine (reference exposure). The primary study endpoint was newly recorded DM, defined as a new diagnosis of DM and use of a DM-specific medication.

Between January 1996 and June 2008, a total of 13,905 participants having a total of 22,493 treatment episodes began 1 of the 4 categories of DMARD regimens.

Incidence rates of new diabetes cases per 1000 person-years were 50.2 for other nonbiologic DMARDs (95% confidence interval [CI], 47.3 - 53.2), 19.7 for TNF inhibitors (95% CI, 19.1 - 20.3), 23.8 for methotrexate (95% CI, 23.0 - 24.6), and 22.2 for hydroxychloroquine (95% CI, 21.3 - 23.1).

Compared with other nonbiologic DMARDs, TNF inhibitors had a multivariate adjusted hazard ratio (HR) for DM of 0.62 (95% CI, 0.42 - 0.91). For methotrexate, the HR was 0.77 (95% CI, 0.53 - 1.13), and it was 0.54 (95% CI, 0.36 - 0.80) for hydroxychloroquine.

"Among patients with RA or psoriasis, the adjusted risk of DM was lower for individuals starting a TNF inhibitor or hydroxychloroquine compared with initiation of other nonbiologic DMARDs," the study authors write.

Limitations of this study include observational design without randomization, likely misclassification of outcome of DM in some participants, and lack of differentiation between type 1 vs type 2 DM.

"The findings from this epidemiologic study should be considered hypothesis-generating," the study authors conclude. "However, considering these results in light of prior findings regarding improved insulin and glucose metabolism and reduced DM risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in DM prevention. A randomized controlled trial testing the ability of these agents to prevent DM among participants with systemic inflammatory disorders should be considered."

Editorial: Prospective Trials Needed

In an accompanying editorial, Tim Bongartz, MD, MS, and Yogish Kudva, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, discuss whether treatment of chronic inflammatory diseases can lower the risk for DM.

"Prospective trials are needed to confirm the observational data and clarify which patients may benefit from these possible [multiple] effects of specific anti-inflammatories," Drs. Bongartz and Kudva write. "If hydroxychloroquine and anti-TNF agents should truly enable 2 complex disease processes to be addressed with a single intervention, it will be crucial to investigate how much of their potential antidiabetic effects would add to good disease control, the durability of these effects, and the timing of treatment. Because even if treatment of chronic inflammatory disease can reduce the risk of diabetes, clinicians still will have to learn how to use specific anti-inflammatory agents to achieve optimal outcomes for both conditions."

The study was supported by an investigator-initiated research grant to Dr. Solomon from Amgen. Some of the other study authors have disclosed various financial relationships with Abbott, Bristol-Myers Squibb, EMD Serono, the National Institutes of Health, UCB, Human Genome Sciences, Pfizer, Ampimmune, Policy Analysis Inc, sanofi-aventis, Novartis, Biogen Idec, Teva, the Agency for Healthcare Research and Quality, the US Food and Drug Administration, HealthCore, and/or WHISCON.

Dr. Bongartz has received grant support from Wyeth and payment for development of educational presentations from Abbott. Dr. Kudva has disclosed no relevant financial relationships.

JAMA. 2011;305:2525-2531, 2573-2574. Full text, Editorial Extract

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