COMPARATIVE EFFECTIVENESS AND SAFETY OF BIOLOGICS IN THE TREATMENT OF ASTHMA

Abstract

Background Evidence on the comparative effectiveness, and safety of monoclonal antibodies, ‘biologics’, approved for the treatment of severe asthma is lacking. Objectives To quantify the comparative effectiveness and safety of biologics approved for the treatment of asthma. Methods Systematic review and a Bayesian network meta-analysis of mepolizumab, benralizumab, and dupilumab in the treatment of eosinophilic asthma. Subsequently, we conducted a target trial emulation to compare omalizumab, mepolizumab, and dupilumab using data from the electronic health records (EHR) of a large health system in the US. Finally, we examined adverse events associated with switching between biologics. Results In individuals with eosinophils ≥300 cells per microliter, dupilumab and mepolizumab ranked highest in reducing exacerbation rates and improving lung function. In individuals with eosinophils of 150-299 cells per mcl, dupilumab and benralizumab ranked highest. These differences however did not meet minimal clinically important thresholds. Dupilumab had the highest overall rank and the highest incidence of adverse events. In the target trial emulation study, dupilumab had a lower cumulative incidence of exacerbations compared to omalizumab (Hazard ratio, HR, 95% confidence interval [CI]: 0.54, 0.32-0.91) and mepolizumab (0.34, 0.22-0.54). Eleven percent (116 of 1,032) of individuals who received one of these biologics switched to another biologic due to an adverse event. These 116 individuals accounted for 143 switches over 28661 person-months (5.0 switches per 1000 person-months). The median time to discontinuation due to adverse events was 8.3 months [[CI, 2.1-26.7] and 17.8 months [6.7-38.2] for other reasons (HR, 0.52, CI 0.28-0.98). Younger age (HR 0.94, CI 0.89-0.98) and female sex were associated with a higher cumulative incidence of switching for safety-related reasons (HR 13.5, CI 7.7-23.5). Conclusions Dupilumab may be more effective than omalizumab, mepolizumab, and benralizumab in improving asthma-related outcomes. However, these differences are minimal. Serious adverse events to these biologics are rare