Adalimumab May Increase HbA1c Levels in Patients with RA without Diabetes

SAN DIEGO, CA—Do tumor necrosis factor inhibitors (TNFi) improve HbA1c in patients with rheumatoid arthritis? The answer depends on the agent and on whether patients have diabetes mellitus, according to a study presented at the 2013 ACR/ARHP Annual Meeting.

Paola de Pablo, MD, MPH, PhD, of the University of Birmingham, College of Medical & Dental Sciences, Queen Elizabeth Hospital, UHB NHS FTr Trust, Birmingham, UK, and colleagues noted that some disease-modifying anti-rheumatic drugs (DMARDs)—including TNFis—may improve insulin resistance and risk of diabetes mellitus. “However, it is unknown whether TNFis improve HbA1c in patients with rheumatoid arthritis with or without diabetes mellitus,” they stated.

Using data on HbA1C collected in a randomized trial that compared drug continuation rates for etanercept and adalimumab, they estimated the incidence of diabetes mellitus and studied the impact of therapy on HbA1c. The trial participants had active rheumatoid arthritis and had previously failed to respond to two non-biologic DMARDs (including methotrexate). They were randomized to etanercept or adalimumab and followed every 3 months for 1 year. Primary end point was newly recorded diabetes, defined as HbA1c ≥48mmol/mol (≥6.5%) on two separate visits.

Of 125 patients with active rheumatoid arthritis randomized to etanercept or adalimumab, 6 (4.8%) had diabetes mellitus and 88% were rheumatoid factor/anti-citrullinated protein antibody (RF/ACPA) positive. Of 119 patients without diabetes mellitus, 7 (5.9%) were diagnosed at baseline. A total of 73 patients (73% female) completed 1 year of treatment with TNFi therapy. Mean age was 54 years; mean BMI, 27.8kg/m2; and mean HbA1c 37.1mmol/mol. Of these, 4 patients (5%) had diabetes mellitus at baseline.

The majority of patients (67%) were on methotrexate; 33% were on prednisolone. Baseline characteristics were similar for patients who were allocated to adalimumab (52%) or etanercept (48%); however, more patients on etanercept were on prednisolone (49% vs. 18%; P=0.006) and more patients on adalimumab were on hydroxychloroquine (24% vs. 3%; P=0.01).

After adjusting for baseline HbA1c, age, sex, BMI, prednisolone dose and TNFi among patients without diabetes, those taking adalimumab had a significant increase in HbA1c levels between baseline and 12 months (P≤0.01), they reported. In contrast, etanercept therapy did not influence HbA1c levels over time. High risk of diabetes (HbA1c 42—47mmol/mol) was significant for adalimumab at Month 6 (P=0.02). A total of 3% of patients had an HbA1c ≥6.5% on at least two occasions.

“The incidence of diabetes (defined by HbA1c) in patients entering a randomized trial of etanercept and adalimumab was considerably higher than other recent data, with 29 new cases per 1000-person years,” Dr. de Pablo noted. “Treatment with a TNFi did not improve HbA1c levels with either agent in diabetics and non-diabetics after 1 year. After excluding those with diabetes and allowing for other factors, patients on adalimumab had higher HbA1c.”

After 1 year of TNFi treatment, age was associated with HbA1c independent of baseline HbA1c, sex, BMI, and prednisolone dose.