In many (but not all) patients with uncontrolled asthma, activated eosinophils are present in high numbers in the airways. Steroids don’t do much to reduce the eosinophils’ numbers or activity, the presumed mechanism for their poor asthma control.
Reslizumab is a humanized monoclonal antibody against IL-5, which plays a key role in eosinophils’ maturation, recruitment, and activation. When tried on all comers with uncontrolled asthma (i.e., all phenotypes), twice, reslizumab reduced eosinophils but had little or no effect on signs or symptoms of asthma. So investigators Mario Castro et al, backed by Ception Pharmaceuticals (since bought by Cephalon), tried the drug again in patients with uncontrolled asthma with the eosinophilic phenotype, where it might be expected to have a greater benefit.
They randomized 106 patients (from 25 sites) with uncontrolled eosinophilic asthma (positive bronchodilator/methacholine test; Asthma Control Questionnaire > 1.5 on high-dose inhaled steroid plus another agent; >=3% eosinophils in induced sputum) to receive an infusion of reslizumab or placebo once a month for 4 months.
They didn’t reach their enrollment goal of 120 to achieve statistical power of 90% to detect a difference of 0.5 in the ACQ, their primary endpoint.
- Primary endpoint of patient-defined asthma control: 59% of patients receiving reslizumab had a 0.5 point improvement in ACQ, while 40% of those receiving placebo did. This missed stat.significance (odds ratio 2, p=0.09).
- Spirometry (secondary endpoint): Patients taking reslizumab had a relative 240 mL improvement in prebronchodilator FEV1, an improvement of 8% predicted. FVC went up by a relative 271 mL.
- Reslizumab reduced sputum and blood eosinophil counts to near zero (95% reduction in sputum, vs. 38% for placebo), a secondary endpoint.
- Fewer patients in the reslizumab group experienced asthma exacerbations (8% vs. 19%), but this also missed stat.significance (p=0.08)
More people reported mild/moderate “nasopharyngitis” in the reslizumab group, but there were no serious adverse events and it seemed generally well-tolerated.
Reslizumab improved lung function in uncontrolled asthmatics with high sputum eosinophils, with a non-significant trend toward improvement in signs/symptoms of asthma. Those with nasal polyposis (a group pre-specified in the study design) experienced a greater benefit in ACQ that did reach stat.significance.
Castro M et al. Reslizumab for Poorly Controlled, Eosinophilic Asthma. A Randomized, Placebo-controlled Study. Am J Respir Crit Care Med 2011;184:1125-1132.