medwireNews: Treatment with the interleukin (IL)-6 receptor inhibitor sarilumab is associated with a greater improvement in glycemic control than conventional DMARDs or adalimumab among patients with comorbid rheumatoid arthritis (RA) and diabetes, indicate findings from a post-hoc analysis.
Mark Genovese (Stanford University Medical Center, Palo Alto, California, USA) and co-investigators analyzed data from three phase 3 randomized controlled trials of sarilumab in RA patients. Two of the trials were placebo controlled; MOBILITY investigated sarilumab versus placebo on a background of methotrexate, while TARGET compared sarilumab with placebo on a background of conventional DMARDs. MONARCH was a monotherapy study comparing sarilumab with the tumor necrosis factor (TNF) inhibitor adalimumab.
Across the three trials, 8.7% of the 2112 participants had concomitant diabetes, defined as a medical history of the disease or baseline use of diabetes drugs.
Overall, participants treated with sarilumab every 2 weeks experienced a greater reduction in glycated hemoglobin (HbA1c) levels from baseline to week 24 than those given placebo, with a least squares mean (LSM) difference of 0.28% and 0.42% for the 150 mg and 200 mg doses, respectively. When participants with diabetes were analyzed separately, the LSM between-group differences were a corresponding 0.47% and 0.67%.
Similarly, patients given sarilumab monotherapy 200 mg achieved a greater reduction in HbA1c levels than those given adalimumab, with a LSM difference of 0.13% for the overall study population, and 0.43% for those with diabetes.
Genovese and team note that reductions in HbA1c levels “were more prominent” with sarilumab versus comparator agents among patients with elevated HbA1c (≥7%) at baseline, “supporting the possibility of improving, as well as maintaining, glucose homeostasis.”
In all three studies, sarilumab was associated with reductions in HbA1c irrespective of whether or not patients achieved RA remission (DAS28-CRP <2.6 points) or low disease activity (DAS28-CRP <3.2 points), and the team did not observe substantial correlations between changes in HbA1c and measures of change in RA disease activity and inflammation, including CRP, CDAI, DAS28-CRP, and tender and swollen joint counts.
“These results support an effect of sarilumab in reducing HbA1c that is independent of anti-inflammatory effects, although some degree of association between general effects on inflammation and changes in glycaemia cannot be ruled out,” write the researchers in Arthritis Research & Therapy.
The team concludes: “Prospective randomised clinical trials are needed to evaluate the effects of IL-6 [receptor] inhibition on glycaemic indices, insulin sensitivity and pancreatic β cell function in patients with comorbid RA and diabetes and determine the clinical relevance of differences in IL-6 [receptor], IL-1β and TNF inhibition.”
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