Comparative Effectiveness of Mepolizumab, Benralizumab and Dupilumab among Patients with Difficult-to-Control Asthma.

Rationale The comparative effectiveness of biologics used as add-on therapy in the management of difficult-to-control asthma is unclear. Objective To compare the effectiveness of dupilumab, mepolizumab and benralizumab among patients with difficult-to-control asthma. Methods Retrospective multicenter cohort study of adult patients with difficult-to-control asthma started on dupilumab, mepolizumab or benralizumab from a multicenter electronic health record and claims-based database between October 19, 2018 and September 30, 2022. Propensity score matching was used to minimize bias from non-randomized treatment assignment; prespecified alpha level was set at 0.017 to account for three primary comparisons. The exposure of interest was new initiation of dupilumab, benralizumab or mepolizumab. The primary outcome was the rate of asthma exacerbation in the year following initiation of biologic therapy modeled using a negative binomial approach. Results Among 893,668 patients with asthma who were prescribed an inhaled corticosteroid and were at least 12 years old, (65% female, mean age 49), 3,943 started dupilumab, 1,902 started benralizumab, and 2,012 started mepolizumab without an alternative indication for biologic therapy. After matching, there were 1,805 patients in each group for comparisons between dupilumab and benralizumab, 1,865 for comparisons between dupilumab and mepolizumab, and 1,721 for comparisons between mepolizumab and benralizumab. For all pairwise comparisons, covariates were well balanced after matching (all standardized mean differences <0.1). Patients initiating dupilumab had a significantly lower rate of asthma exacerbations (1.07/year) compared to benralizumab (1.47/year) with a rate ratio of 0.73 [95% confidence interval (CI) 0.63-0.85] and also had a significantly lower rate of asthma exacerbations compared to mepolizumab (1.04/year compared to 1.45/year) with a rate ratio of 0.72 [0.62-0.84]. There was no statistically significant difference in the rate of asthma exacerbations between mepolizumab (1.40/year) and benralizumab (1.41/year) with a rate ratio of 1.00 [CI 0.85-1.17]. Conclusions In patients with difficult-to-control asthma newly initiated on biologic therapy, dupilumab was associated with a decreased rate of asthma exacerbations in the year after initiation as compared with mepolizumab or benralizumab.