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

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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%).

CONCLUSIONS: 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.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01508936; URL: www.clinicaltrials.gov.