B32-53 Indirect Treatment Comparison of Tezepelumab Versus Other Biologics for the Treatment of Severe Asthma in Asia

Rationale

Indirect treatment comparisons (ITCs) were performed to evaluate the comparative efficacy of tezepelumab versus other biologics in patients with severe uncontrolled asthma.

Methods

Data on the efficacy of the biologics versus placebo were obtained from phase 3 randomized controlled trials (RCTs) conducted in Asia or reporting Asian patient populations. Anchored matching-adjusted indirect comparisons (MAICs) were performed, in which the tezepelumab population was adjusted for three effect modifiers, namely past exacerbations, eosinophil level and age, to account for differences from the included populations of competitor trials. These three effect modifiers were selected based on their known role in modifying treatment effects across the included biologics, while also taking into consideration the need to apply a common set of effect modifiers across comparisons and to avoid excessive loss of effective sample size (ESS) resulting from model overspecification. Outcomes of interest included the overall annualized asthma exacerbation rate (AAER) and the AAER for exacerbations leading to hospitalization or emergency visits. Treatment effects of tezepelumab over other comparator biologics were reported as rate ratios (RRs) with 95% confidence intervals. Effective sample size was calculated to quantify information loss in the process of population adjustment.

Results

In addition to the DIRECTION trial (NCT03927157) for tezepelumab, six RCTs (dupilumab n = 1, benralizumab n = 1, mepolizumab n = 1, omalizumab n = 1 and depemokimab n = 2) were included in the ITCs. Findings from the anchored MAICs are summarized in Table 1. Across comparisons, tezepelumab was consistently associated with numerically lower overall AAERs compared with other biologics, with statistically significant reductions versus mepolizumab and depemokimab. For AAER leading to hospitalization or emergency visits, results showed broadly comparable efficacy between tezepelumab and other biologics; although point estimates numerically favoured tezepelumab, confidence intervals were wide, potentially due to the low frequency of such events in the included trials.

Conclusions

Consistent with the findings from global network meta-analyses, these ITCs based on Asian clinical trials suggest that tezepelumab tends to offer greater reductions in asthma exacerbation rates compared with other biologics in patients with severe uncontrolled asthma.

This abstract is funded by: AstraZeneca and Amgen