Two trials provide new insights on fixed-dose subcutaneous reslizumab for severe asthma

A fixed dose of 110 mg subcutaneous reslizumab was ineffective in reducing exacerbation frequency and daily maintenance oral corticosteroid dose in patients with severe eosinophilic asthma, according to data from two trials.

“Reslizumab given as a fixed-dose (110 mg) subcutaneous injection was not effective in reducing exacerbation rates in patients with uncontrolled asthma and an increased blood eosinophil count or in reducing the daily maintenance oral corticosteroid dose in patients with oral corticosteroid-dependent severe eosinophilic asthma,” Jonathan A. Bernstein, MD, professor in the department of internal medicine in the division of immunology/allergy section at the University of Cincinnati College of Medicine and Bernstein Clinical Research Center in Cincinnati, and colleagues wrote in The Lancet Respiratory Medicine.

Researchers conducted two randomized, double-blind, placebo-controlled, parallel-group phase 3 trials to evaluate safety and efficacy of subcutaneous reslizumab (Cinqair, Teva Respiratory) 110 mg.

The first study included 468 patients with uncontrolled severe asthma, at least two asthma exacerbations in the prior year, blood eosinophil count of 300 cells/µL or more and at least a medium dose of inhaled corticosteroids with one or more additional asthma controllers.

The second study included 177 patients with severe asthma, blood eosinophil count of 300 cells/µL or more, daily maintenance oral corticosteroid and high-dose inhaled corticosteroids in addition to another controller.

Patients were randomly assigned 110 mg subcutaneous reslizumab (n = 232 in study 1; n = 88 in study 2) or placebo (n = 236 in study 1; n = 89 in study 2) every 4 weeks. Treatment duration was 52 weeks in the first study and 24 weeks in the second study. Patients continued their normal inhaled asthma controller regimen throughout the study periods.

In the first study, the researchers reported no differences in the intention-to-treat population in frequency of asthma exacerbations during the 52-week period with subcutaneous reslizumab or placebo (RR = 0.79; 95% CI, 0.56-1.12; P = .19). However, fixed-rate reslizumab reduced exacerbation frequency in a subgroup of patients with eosinophil counts of 400 cells/µL or more (RR = 0.64; 95% CI, 0.43-0.95). Patients with higher trough serum reslizumab concentrations had larger reductions in annual exacerbation risk (P = .0035) and longer time to first exacerbation.

In the second study, the researchers reported no difference between subcutaneous reslizumab and placebo in percent reduction in daily oral corticosteroid dose (OR for lower category of use with reslizumab vs. placebo = 1.23; 95% CI, 0.7-2.16; P = .47).

Adverse events and serious adverse events were similar with subcutaneous reslizumab and placebo.

“Exposure-response analyses indicate that to achieve the magnitude of effect on clinical asthma exacerbations observed with intravenous reslizumab 3 mg/kg, systemic reslizumab concentrations higher than those achieved with subcutaneous 110 mg are required. The use of higher, weight-based doses of subcutaneous reslizumab should be assessed in future studies,” the researchers wrote.

IV reslizumab 3 mg/kg is FDA approved for treatment of severe eosinophilic asthma.