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Sarilumab plus DMARDs reduces fasting glucose, HbA1c in RA patients with diabetes

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Mark C. Genovese

SAN DIEGO — Use of the IL-6 inhibitor sarilumab with disease-modifying antirheumatic drugs appears to reduce fasting glucose and HbA1c in RA patients with diabetes, and reduce HbA1c in those without diabetes, according to findings presented at the 2017 American College of Rheumatology Meeting.

In the study, researchers analyzed data from two placebo-controlled studies: MOBILITY and TARGET. These studies assessed the effects of sarilumab vs. placebo plus DMARDs on fasting glucose and glycosylated HbA1c_.  Both studies excluded patients with HbA1c of 9% or higher.

Patients from MOBILITY and TARGET with an available baseline sample and at least one postbaseline sample were included in post hoc pooled analyses.

“Based on the post hoc as-observed analysis of the patients who had these tests confirmed at baseline and 24 weeks, we specifically looked at what sorts of trends we saw in terms of hemoglobin, A1C and fasting blood glucose,” Mark C. Genovese. MD, of Stanford University Medical Center and a lead author of the study, said in an interview with Healio Rheumatology. “We broke it into two groups and looked at the group that had diabetes vs. the group that didn’t have diabetes.”

The study included patients with diabetes (n=179) and without diabetes (n=1,803). The researchers calculated changes from baseline in fasting glucose, HbA1c and weight. Changes in these measures were stratified by clinical response.

Patients with diabetes had higher baseline body weight (mean 84.8 kg vs. 74.6 kg) compared with patients without diabetes, and the diabetes group had a higher percentage of patients with BMI of 30 kg/m² or higher (56.7% vs. 31.9%). The treatment groups — placebo, 150 mg sarilumab and 200 mg sarilumab — had similar baseline mean fasting glucose and HbA1c, but these measures were higher in patients with diabetes.

The researchers found that at week 24, patients with diabetes had a greater decrease in fasting glucose vs. those without diabetes. Those with and without diabetes who were treated with sarilumab showed reductions in HbA1c, while placebo-treated patients showed no decrease. The diabetes group showed the largest treatment effect.

Patients with diabetes who were treated with 200 mg of sarilumab showed an HbA1c   change of –0.43% at week 24, and the patients with diabetes who received placebo demonstrated a mean HbA1c increase of 0.17% (–0.69% mean difference; P = .001). The sarilumab-treated subgroups showed decreases in fasting glucose and HbA1c regardless of high-sensitivity–CRP changes, ACR50 or DAS28-CRP remission, or mean body weight increases.

“We looked at whether or not the likelihood of response played a role, suggesting that just a decrease in inflammation might have been the trigger, but whether or not a patient had achieved an ACR-response was not correlated with whether or not they had a reduction in hemoglobin A1C or fasting blood glucose measurement,” Genovese said.

Sarilumab displayed similar overall safety in both patients with and without diabetes.

“I think this post-hoc data creates just another point of information that interleukin-6, and the blockade of interleukin-6, can be involved in both glucose and stability of a diabetic patient,” Genovese said. “Whether or not this has true therapeutic ramifications, I have no idea. There are a lot of things that you do in a true, proactive, prospective study to assess diabetic control, and insulin reactivity and resistance were not assessed here.”

Genovese voiced support for further investigation of these “intriguing” data.

“I think that additional studies could and should be done to better understand whether interleukin-6 blockade might have a role in different patients with rheumatoid arthritis and various comorbidities,” he told Healio Rheumatology. “I also recognize that these are expensive studies to do, and it’s unclear to me whether any sponsor would want to go in that direction.” – by Jennifer Byrne

Reference:

Genovese MC, et al. Abstract 1822; Presented at: American College of Rheumatology Annual Meeting; Nov. 4-8, 2017; San Diego.

Disclosure: Please see the full study for a list of relevant disclosures.