Hydroxychloroquine use and decreased risk of diabetes in rheumatoid arthritis patients.

BACKGROUND/OBJECTIVES: Several studies have associated hydroxychloroquine use with decreased risk of diabetes mellitus (diabetes) or improved glycemic control in rheumatoid arthritis patients, but the studies were small or used data from self-report. The present study sought to replicate this protective relationship in a health system using electronic health records with laboratory data and physician diagnoses. METHODS: This study is a retrospective cohort of 1127 adults with newly diagnosed rheumatoid arthritis and no diabetes within the Geisinger Health System between January 1, 2003, and March 31, 2008. Patients were classified as ever users (n = 333) or never users (n = 794) of hydroxychloroquine. Incident diabetes cases were defined using 2010 American Diabetes Association criteria. RESULTS: The median follow-up times for the ever and never hydroxychloroquine users were 26.0 and 23.0 months, respectively (P = 0.28). The median duration of hydroxychloroquine exposure was 14.0 months. Of the 48 cases developing diabetes during observation, 3 were exposed to hydroxychloroquine at time of development and 45 were nonexposed, yielding incidence rates of 6.2 and 22.0 per 1000 per year (P = 0.03), respectively. In time-varying Cox proportional hazards regression models adjusting for sex, age, body mass index, positive rheumatoid factor and anti-cyclic citrullinated peptide antibodies, erythrocyte sedimentation rate, and nonsteroidal anti-inflammatory drug, glucocorticoid, methotrexate, and tumor necrosis factor α inhibitor use, the hazard ratio for incident diabetes among hydroxychloroquine users was 0.29 (95% confidence interval, 0.09-0.95; P = 0.04) compared with nonusers. CONCLUSIONS: Our findings support the potential benefit of hydroxychloroquine in attenuating the risk of diabetes in rheumatoid arthritis patients. Further work is needed to determine its potential preventive role in other groups at high risk for diabetes.

Diabetes mellitus risk in rheumatoid arthritis: reduced incidence with anti-tumor necrosis factor α therapy.

OBJECTIVE: To examine the association of tumor necrosis factor α (TNFα) inhibitor use and the risk of developing diabetes mellitus in a rheumatoid arthritis (RA) inception cohort. METHODS: Adults diagnosed with RA between January 1, 2001, and December 31, 2009, were identified (n = 1,881). Prevalent cases of diabetes mellitus (n = 294) were excluded. Information on sociodemographic data, medical history, body mass index (BMI), laboratory measures, and medications was collected from the electronic health record. Incident diabetes mellitus was defined using the 2010 American Diabetes Association criteria or physician-established diagnosis. Time-varying Cox proportional hazards regression models were used to adjust for age, sex, race, BMI, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), and use of nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, hydroxychloroquine, and methotrexate. RESULTS: A total of 1,587 incident RA patients without diabetes mellitus were included. The anti-TNFα users (n = 522) had a lower median age but greater baseline BMI; maximum ESR, RF, and anti-CCP positivity; and NSAID, glucocorticoid, or methotrexate use. The median followup time for the ever and never TNFα inhibitor users was 44.9 months (interquartile range [IQR] 23.7-73.0 months) and 37.1 months (IQR 16.3-65.1 months), respectively (P < 0.001). Of the 91 patients developing diabetes mellitus, 16 were ever and 75 were never TNFα inhibitor users, yielding incidence rates of 8.6 and 17.2 per 1,000 person-years (P = 0.048), respectively. Adjusting for covariates, the hazard ratio for incident diabetes mellitus in TNFα inhibitor users was 0.49 (95% confidence interval 0.24-0.99, P = 0.049) compared to the never users. CONCLUSION: In this inception RA cohort, anti-TNFα use was associated with a 51% reduction in risk of developing diabetes mellitus.

Tumor necrosis factor-α inhibitor use is not associated with lipid changes in rheumatoid arthritis.

OBJECTIVE: To determine the association of use of tumor necrosis factor-α (TNF-α) inhibitors with differences in lipid levels in patients with rheumatoid arthritis (RA). METHODS: We studied 807 patients with incident RA to compare differences in lipid levels in TNF-α inhibitor users versus nonusers, with adjustment for relevant covariables. RESULTS: TNF-α inhibitor use was not associated with differences in levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides, LDL:HDL, or TC:HDL compared to nonusers. CONCLUSION: Use of TNF-α inhibitor was not associated with differences in lipid levels in patients with RA.

Hydroxychloroquine use associated with improvement in lipid profiles in rheumatoid arthritis patients.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in patients with rheumatoid arthritis (RA). Disease-modifying therapies that improve risk factors for CVD, such as dyslipidemia, are desired. This study used an electronic health record to determine if hydroxychloroquine (HCQ) use was associated with an improvement in lipid levels in an inception RA cohort. METHODS: All adult individuals with the initial diagnosis of RA between January 1, 2001, and March 31, 2008, were identified (n=1,539). Only patients with at least one lipid level post-RA diagnosis were included (n=706). Information on demographics, medical history, body mass index (BMI), laboratory measures, and medications were collected at office visits. Potential risk and protective factors for dyslipidemia were controlled for in linear mixed-effects regression models for low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, triglycerides, LDL/HDL, and total cholesterol/HDL. RESULTS: Patients were 69% women and 98% white, with a median age of 65 years and a median BMI of 29.8 kg/m2. In the adjusted regression models, HCQ use was associated with the following average differences in lipids: LDL decrease of 7.55 mg/dl (P<0.001), HDL increase of 1.02 mg/dl (P=0.20), total cholesterol decrease of 7.70 mg/dl (P=0.002), triglycerides decrease of 10.91 mg/dl (P=0.06), LDL/HDL decrease of 0.136 (P=0.008), and total cholesterol/HDL decrease of 0.191 (P=0.006), which were stable over time. CONCLUSION: Use of HCQ in this RA cohort was independently associated with a significant decrease in LDL, total cholesterol, LDL/HDL, and total cholesterol/HDL. Considering these results, its safety profile, and low cost, HCQ remains a valuable initial or adjunct therapy in this patient population at high risk for CVD.