Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts.

Abstract

IL-5, a mediator of eosinophil activity, is an important potential treatment target in patients with uncontrolled asthma. The efficacy of reslizumab, a humanized anti-human IL-5 monoclonal antibody, has been characterized in patients with blood eosinophils ≥ 400 cells/μL. This study further characterizes the efficacy and safety of reslizumab in patients with poorly-controlled asthma, particularly those with eosinophils < 400 cells/μL. Patients were randomly assigned to intravenous reslizumab 3.0 mg/kg or placebo once every 4 weeks for 16 weeks. The primary end point was the change in FEV₁ from baseline to week 16. Secondary measures included Asthma Control Questionnaire-7 (ACQ-7) scores, use of short-acting β-agonists (SABAs), and FVC. Four hundred ninety-two patients received ≥ 1 dose of placebo (n = 97) or reslizumab (n = 395). In the overall population, mean FEV₁ change from baseline to week 16 was not significantly different between reslizumab and placebo, and no significant relationship was detected between treatment, baseline blood eosinophils and change in FEV₁. In the subgroup of patients with baseline eosinophils < 400 cells/μL, patients treated with reslizumab showed no significant improvement in FEV₁ compared with those receiving placebo. In the subgroup with eosinophils ≥ 400 cells/μL, however, treatment with reslizumab was associated with much larger improvements in FEV₁, ACQ-7, rescue SABA use, and FVC compared with the placebo group. Reslizumab was well tolerated, with fewer overall adverse events compared with placebo (55% vs 73%). Reslizumab was well tolerated in patients with inadequately controlled asthma. Clinically meaningful effects on lung function and symptom control were not seen in patients unselected for baseline eosinophils. ClinicalTrials.gov; No.: NCT01508936; URL: www.clinicaltrials.gov.