The Effectiveness and Value of Biologic Therapies for the Treatment of Uncontrolled Asthma

Abstract

conducted a review of omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab as add-on therapy for patients with uncontrolled moderate to severe asthma to coincide with the expected FDA approval of dupilumab. In this article, we summarize the systematic literature review of the clinical effectiveness of the drugs, the cost-effectiveness analysis, and the policy discussion with key stakeholders regarding the overall value of these therapies held at a public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) on November 29, 2018. The detailed report is available on the ICER website at https://icer-review.org/material/asthma-final-evidence-report/. ■■ Summary of Findings Clinical Effectiveness We compared the evidence on the clinical effectiveness of the 5 biologics added to standard of care (inhaled corticosteroids plus at least 1 additional controller therapy) versus standard of care alone. The primary measures of clinical benefit were reductions in asthma exacerbations and improvements in quality of life. The primary harms were severe adverse events and adverse events leading to discontinuation of therapy. There are no head-to-head randomized or observational trials of the 5 biologics. We used summary estimates from Cochrane meta-analyses for each of the drugs, 7,8 in addition to the estimates for dupilumab from its pivotal trials. 9,10 The evidence showed that all 5 drugs reduced the annual exacer-bation rate by approximately 50%, with broadly overlapping confidence intervals. Similarly, the effect on quality of life for all of the drugs, as assessed by the Asthma Quality of Life Questionnaire and by the Asthma Control Questionnaire, was similar, with modest but statistically significant improvements. All 5 of the drugs are more effective in patients with higher baseline eosinophil counts. T he Centers for Disease Control and Prevention estimates that 20.4 million Americans aged ≥ 18 years currently have asthma and that an additional 6.1 million children have asthma. 1,2 There are approximately 14.2 million office visits , 1.8 million emergency department visits, and 440,000 hospitalizations due to asthma each year in the United States. 2 The societal costs are estimated to be $82 billion, which includes $50 billion in direct medical costs, $29 billion from asthma-related mortality, and $3 billion from missed work and school. 2 Severe asthma comprises a small but important subset of all individuals with asthma. Those with severe asthma represent fewer than 5%-10% of all individuals with asthma but account for approximately 50% of all costs. In addition to being treated with inhaled corticosteroids and long-acting beta agonist therapy , these patients are often treated with oral corticosteroids. 3 Asthma has been divided into different phenotypes with some overlap. Approximately half of all patients with asthma have "allergic" asthma, which is associated with allergic rhinitis , atopy, and elevated immunoglobin E (IgE) levels. Another group has "eosinophilic" asthma, with elevated eosinophil levels in blood and airways. Both of these phenotypes are linked to type 2 inflammation with increases in T helper 2 cells. 4 These cells secrete interleukin-4 (IL-4), IL-5, and IL-13, which increase the proliferation, survival, and recruitment of eosino-phils and increase IgE levels. 5,6 There are 5 biologic therapies approved by the U.S. Food and Drug Administration (FDA) that affect the pathways involved in the allergic or eosinophilic phenotypes of asthma. These drugs, along with their mechanisms of action and their FDA indications for asthma, are summarized in Table 1. Omalizumab is a monoclonal antibody to IgE, which is indicated for the treatment of patients with moderate to severe asthma with the allergic phenotype. Mepolizumab, reslizumab, and benralizumab target the IL-5 pathway either with mono-clonal antibodies to IL-5 itself (mepolizumab and reslizumab) or to the IL-5 receptor (benralizumab). Dupilumab is a mono-clonal antibody to the IL-4 receptor alpha, which modulates the IL-4 and IL-13 pathways.