Reslizumab in the treatment of inadequately controlled asthma in adults and adolescents with elevated blood eosinophils: clinical trial evidence and future prospects

Abstract

Eosinophils have long been implicated as playing a central role in the pathophysiology of asthma in many patients, and eosinophilic asthma is now recognized as an important asthma endotype. Eosinophil differentiation, maturation, migration, and survival are primarily under the control of interleukin-5 (IL-5). Reslizumab is a humanized monoclonal (immunoglobulin G4/κ) antibody that binds with high affinity to circulating human IL-5 and downregulates the IL-5 signaling pathway, potentially disrupting the maturation and survival of eosinophils. In 2016, an intravenous formulation of reslizumab was approved in the USA, Canada, and Europe as add-on maintenance treatment for patients aged ⩾18 years with severe asthma and with an eosinophilic phenotype. The efficacy of reslizumab as add-on intravenous therapy has been reported in several phase III studies in patients with inadequately controlled moderate-to-severe asthma and elevated blood eosinophil counts (⩾400 cells/µl). Compared with placebo, reslizumab was associated with significant improvements in clinical exacerbation rate, forced expiratory volume in 1 s, asthma symptoms and quality of life, and significant reductions in blood eosinophil counts. Reslizumab also demonstrated a favorable tolerability profile similar to that of placebo, with reported adverse events being mostly mild to moderate in severity. Ongoing studies are focusing on the evaluation of a subcutaneous formulation of reslizumab in patients with asthma and elevated eosinophil levels. This review discusses the preclinical and clinical trial data available on reslizumab, potential opportunities for predicting an early response to reslizumab, and future directions in the field of anti-IL-5 antibody therapy.

Keywords: antibodies; asthma endotype; eosinophilic asthma; interleukin-5; monoclonal; reslizumab; safety; treatment outcome.

Figure 1.

Schematic depicting role of IL-5 in promoting eosinophilic asthma.

Figure 2.

Changes in FEV₁ and AQLQ over 52 weeks in patients receiving reslizumab or placebo in Study 3082 (A, C) and Study 3083 (B, D). AQLQ, asthma quality of life questionnaire; FEV₁, forced expiratory volume in 1 s; LS, least-squares; *p < 0.05. ^†p < 0.01 versus placebo. Reproduced with permission of Elsevier, from Castro and colleagues; permission conveyed through Copyright Clearance Center, Inc.