Patients with rheumatoid arthritis (RA) are at increased risk for diabetes compared with the general population, and may exhibit both reduced insulin sensitivity and impaired beta-cell function. Interleukin (IL)-6 signaling has pleotropic effects, including on glucose metabolism, and is an independent risk factor for type 2 diabetes. Therefore, this study explored the effects of sarilumab, an anti–IL-6Rɑ human monoclonal antibody, or placebo in combination with disease-modifying antirheumatic drugs (DMARDs) on fasting glucose and glycosylated hemoglobin (HbA1c) in diabetic and nondiabetic patients with RA. Sarilumab is currently approved for the treatment of RA based on its efficacy and safety demonstrated in several trials, including the MOBILITY (parts A and B; n = 1436) and TARGET (n = 546) studies of sarilumab (150 mg and 200 mg every 2 weeks) plus DMARDs.
Fasting glucose and HbA1c data from eligible patients were collected during the placebo-controlled period of the MOBILITY and TARGET studies of sarilumab plus DMARDs; data from the open-label sarilumab treatment part of the study were not included. Based on medical history of diabetes or prior use of antidiabetic medication, patients with baseline and ≥1 postbaseline samples were classified into diabetic and nondiabetic subgroups; patients with HbA1c ≥9 were excluded from the analysis. A linear regression model was used to analyze changes from baseline in fasting glucose, HbA1c, and weight; these were stratified by clinical response. A determination of “clinical meaningfulness” was based on comparison with results of clinical trials with effective antidiabetic medications.
The current analysis included 179 diabetic and 1803 nondiabetic patients with RA. At baseline, the diabetic group had a higher body weight compared with the nondiabetic group, with a larger proportion of patients with body mass index ≥30 kg/m2. As expected, the mean fasting glucose and HbA1c at baseline were higher in the diabetic group than in the nondiabetic group across the 3 treatment groups (sarilumab 150 mg, sarilumab 200 mg, and placebo).
Following sarilumab treatment (both doses), patients in both the diabetic and nondiabetic groups achieved reductions in HbA1c at week 24 compared with those in the nondiabetic group, with the largest treatment effect seen in the diabetic group; such reductions did not occur with placebo in both groups.
Sarilumab-treated patients in the diabetic group also showed decreased mean fasting glucose levels; the nondiabetic group did not show decreases in fasting glucose levels. Moreover, an increase in body weight of <2% was observed and was similar in diabetic and nondiabetic patients. All changes in HbA1c and fasting glucose at week 25 were independent of glucocorticoid use or clinical response.
Based on these results of the post-hoc analyses, the authors concluded that sarilumab plus DMARD treatment resulted in significant reductions in HbA1c in both diabetic and nondiabetic patients with RA. Significant lowering of fasting glucose levels was only achieved in diabetic patients with RA.
Genovese MC, et al. ACR 2017. Abstract 1822.