Sarilumab linked to greater reduction of HbA1c in patients with RA
Sarilumab is associated with a greater reduction in glycosylated hemoglobin among patients with rheumatoid arthritis, with or without diabetes, compared with DMARDs or adalimumab, according to findings in Arthritis Research & Therapy.
“The incidence of type 2 diabetes (T2D) is higher in patients with RA (17–20%) than in the general population (8%), independent of glucocorticoid use,” Mark C. Genovese, MD, of the Stanford University Medical Center, and colleagues wrote. “Patients with RA also have increased insulin resistance compared with individuals without RA. RA disease outcomes are poorer in patients with comorbid diabetes, who are also at increased risk for cardiovascular disease relative to patients who have either RA or diabetes only.”
“Medical management of T2D and RA can be complicated by the potential effects of RA treatments on glucose levels,” they added. “Oral glucocorticoids increase the risk for diabetes in patients with RA because of the adverse metabolic actions of these drugs, with higher dose and longer treatment duration increasing the risk. By contrast, the anti-inflammatory drug hydroxychloroquine reduced the risk of incident diabetes in patients with RA and was also associated with a favorable effect on glycaemia in patients with RA in the absence of diabetes.”
To compare the effects of the IL-6 inhibitor sarilumab (Kevzara; Regeneron, Sanofi) to TNF inhibitors on glycosylated hemoglobin (HbA1c) among patients with RA, with or without diabetes, Genovese and colleagues conducted a post hoc analysis of three phase 3 studies. According to the researchers, two of the studies were placebo-controlled trials of subcutaneous sarilumab administered in doses of 150 or 200mg once every 2 weeks, plus methotrexate, or conventional synthetic DMARDs. The third study was a monotherapy trial of sarilumab in doses of 200 mg every 2 weeks, compared with 40 mg of adalimumab (Humira, AbbVie).
The presence of diabetes was identified through participants’ medical history or the use of anti-diabetic medication. Patients with an HbA1c of 9% or greater were excluded from all three trials. In those trials, HbA1c was assessed at baseline and at weeks 12 and 24. In all, the researchers analyzed data from 184 patients with diabetes and 1,928 without diabetes.
According to the researchers, participants with diabetes were older, weighed more and demonstrated higher RA disease activity, compared with those without diabetes. However, regardless of diabetes status, participants on background conventional synthetic DMARDs demonstrated a least-squares mean-difference change in HbA1c of –0.28 (95% CI, –0.4 to –0.16) from baseline to week 24 with 150-mg doses of sarilumab, compared with the placebo group. Among those who received 200 mg of sarilumab the least-squares mean-difference change was –0.42 (95% CI, –0.54 to –0.31).
Without conventional synthetic DMARDs, the least-squares mean-difference for 200 mg of sarilumab, compared with adalimumab, was –0.13 (95% CI, –0.22 to –0.04) at week 24.
Patients with diabetes and/or a baseline HbA1c of 7% or more demonstrated a greater reduction in HbA1c at week 24 with sarilumab than with placebo or adalimumab. Genovese and colleagues found no correlation between baseline — or change from baseline — HbA1c and baseline — or change from baseline — C-reactive protein, 28-joint Disease Activity Score, or hemoglobin, nor between HbA1c change from baseline and baseline glucocorticoid use. A history of diabetes, or use of diabetes treatments, had a limited effect on safety and efficacy with sarilumab.
“IL-6R inhibition with sarilumab was associated with a reduction in HbA1c in patients with RA with and without comorbid diabetes that were greater than with placebo or adalimumab and could not be attributed solely to changes in CRP, disease activity or hemoglobin,” Genovese and colleagues wrote.
“The safety and efficacy of sarilumab in patients with diabetes were consistent with the results for prespecified patient populations in the individual studies,” they added. “Prospective randomized clinical trials are needed to evaluate the effects of IL-6R inhibition on glycemic indices, insulin sensitivity and pancreatic cell function in patients with comorbid RA and diabetes and determine the clinical relevance of differences in IL-6R, IL-1 and TNF inhibition.”