The new anti-interleukin-1beta monoclonal antibody, gevokizumab, reduces hs-crp in subjects with type 2 diabetes mellitus

Abstract

The new anti-interleukin-1β (IL-1β) monoclonal antibody, gevokizumab, was evaluated in patients with type 2 diabetes mellitus (T2DM) not adequately controlled on stable metformin treatment. In a parallel-group, double-blind, placebocontrolled phase II trial, 421 patients were randomized to monthly subcutaneous injections of placebo or gevokizumab at doses of 0.01, 0.03, 0.1, or 0.3 mg/kg for 6 months. The principal objective in terms of reduction of hemoglobin A1c was not reached. By contrast 6 months' treatment with gevokizumab was associated with a significant decrease in high-sensitivity C-reactive protein (hs-CRP) in all groups versus placebo (all p<0.02). The proportion of patients with more than 60% reduction in hs-CRP increased in a dose-dependent manner to 39% and 40% of patients treated with 0.1 and 0.3 mg/kg, respectively (both p<0.0001). Gevokizumab was well tolerated. There were no drug-related serious adverse events or injection site reactions. Incidences of infection in the gevokizumab and placebo groups were comparable (26% vs 23%); nasopharyngitis was the most frequent (5% vs 4%). Gevokizumab, a humanized monoclonal antibody that modulates IL-1β, has been demonstrated to have a marked anti-inflammatory effect, reflected by a substantial reduction in hs-CRP in patients with T2DM. A dose-response effect was found in terms of proportion of patients with reduced hs-CRP. The decrease observed in the inflammatory status of such patients indicates potential cardiovascular beneficial effects, which merits further exploration. ∗p<0.0001 and ∗∗p<0.003 Chi-Square test.