Tezepelumab compared with other biologics for the treatment of severe asthma: a systematic review and indirect treatment comparison

Aims To compare the efficacy of tezepelumab with other approved biologics via indirect treatment comparisons (ITCs) in patients aged >= 12 years with severe uncontrolled asthma. Materials and methods Data from randomized controlled trials (RCTs) identified from a systematic literature review were synthesized using two different ITC approaches: network meta-analysis (NMA) and simulated treatment comparison (STC). Outcomes of interest were annualized asthma exacerbation rate (AAER) and AAER for exacerbations leading to hospitalization. To address potential heterogeneity between study populations, various subgroup analyses were performed for the NMA (based on blood eosinophil count, fractional exhaled nitric oxide level, and presence of allergic asthma), and for the STC, models were adjusted for potential treatment effect modifiers. Sensitivity analyses were performed to assess the impact of study design (exclusion of non-placebo-controlled studies and non-phase 3 or 4 studies). Results were reported as rate ratios (RRs) with 95% credible/confidence intervals and ranking statistics were computed for the NMAs. Results Sixteen RCTs were included in at least one of the ITCs. All biologics (tezepelumab, dupilumab, benralizumab, mepolizumab, reslizumab, and omalizumab) had similar efficacy, with no statistically significant RRs for either exacerbation outcome; however, tezepelumab was favorably associated with numerically lower AAERs and was ranked first in the network for both types of exacerbation outcome. This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab. Limitations Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, the impact on findings is expected to be low, based on consistency across analyses. Conclusions Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.