Reslizumab, an IgG4 kappa humanized monoclonal antibody that targets interleukin-5 to disrupt the maturation, activation, and survival of eosinophils, is effective in patients with asthma who are oral-corticosteroid dependent. It is also associated with reductions in the population-wide systemic corticosteroid burden, supporting the benefit of add-on therapy with biologics for individuals with severe oral-corticosteroid–dependent asthma, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Although phase 3 clinical trials have demonstrated that reslizumab is effective for patients with inadequately controlled eosinophilic asthma, limited data have been published on its efficacy in oral-corticosteroid–dependent patients. This post hoc analysis of pooled data from duplicate, phase 3, placebo-controlled trials was designed to assess the efficacy of reslizumab in this population, as well as the benefits on oral corticosteroid burden. For these trials, patients with inadequately controlled, moderate-to-severe asthma who were aged 12 years to 75 years (N=953) were randomly assigned 1:1 to receive placebo (n=476 [244 in study 1 and 232 in study 2]) or intravenous reslizumab 3.0 mg/kg (n=477 [245 and 232, respectively]) every 4 weeks for 52 weeks, stratified by oral corticosteroid use at enrollment and by region.
In each group, 15% (n=73) of patients were taking maintenance oral corticosteroids at baseline, with a median dose of 7 mg (Q1 5 mg; Q3 10 mg; interquartile range, 5 mg). Reslizumab was superior to placebo for all efficacy end points, with numerically greater improvements among patients who were oral corticosteroid dependent compared with the overall population. The strongest positive predictor of reduced risk of exacerbation with reslizumab vs placebo was having ≥2 vs 1 clinical asthma exacerbation in the past 12 months (risk reduction 77.5%; 95% CI, 58.0%-88.0% vs 15.2%; 95% CI, -150.2% to 71.2%; P =.028). Significantly fewer new prescriptions for systemic corticosteroids were issued per patient in the reslizumab group compared with placebo (mean ± standard deviation, 0.5±1.07 vs 1.0±1.52; P <.0001), and both total cumulative systemic corticosteroid dose and per-patient cumulative dose burdens were lower: 121,135 vs 290,977 mg and 254 vs 611 mg/patient, respectively (both P <.0001 for reslizumab vs placebo). Of the 73 patients in each group who were taking oral corticosteroids at baseline, 61 in the reslizumab group and 65 in the placebo group experienced at least 1 adverse event.
Study investigators concluded that although these findings do suggest a benefit of reslizumab therapy in oral corticosteroid-dependent severe asthma, their results “are yet to be confirmed in clinical trials of [intravenous] reslizumab, and this will require further prospectively designed studies. Importantly, a statistically significant and clinically relevant lower burden of [systemic corticosteroid] use was seen in patients receiving reslizumab compared with those receiving placebo. This finding was noted in the overall population as well as in patients in at-risk subgroups, including individuals with high body weight.”
Disclosure: This study was supported by Teva Pharmaceuticals, Inc. Please see the original reference for a full list of authors’ disclosures.
Nair P, Bardin P, Humbert M, et al. Efficacy of intravenous reslizumab in oral corticosteroid-dependent asthma [published online October 15, 2019]. J Allergy Clin Immunol Pract. doi: 10.1016/j.jaip.2019.09.036