OBJECTIVES: Severe asthma is a heterogeneous, complex disease that significantly impacts patients’ ability to pursue daily activities. Biologic treatments have demonstrated improvement in outcomes and reduction of corticosteroid treatment burden. This review aimed to understand the evaluation of submissions by HTA agencies for biologics and to identify gaps in clinical and economic evidence submitted for severe asthma.

METHODS: NICE, SMC, HAS, IQWiG/G-BA, CADTH, and ICER websites were reviewed for HTA appraisals of biologics in severe asthma. Critiques regarding population, comparators, effectiveness, safety, utilities, model structure, and inputs were collected.

RESULTS: A total of 24 appraisals were identified for omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab. Among the 22 appraisals providing reimbursement recommendations, 15 had a positive outcome. In the absence of head-to-head trials, indirect comparisons between biologics were deemed highly uncertain and not suitable for decision-making due to differences in the target population. Thus, the comparison with standard of care (SOC) was considered appropriate in most appraisals. All IQWiG/G-BA appraisals concluded that added benefit was not proven due to insufficient data for comparator SOC therapy or lack of generalizability of the trial population. ICER noted uncertainty in long-term safety and effectiveness, and insufficient data for subgroups of elderly patients, or Black Americans. ICER and HAS critiqued the absence of a standard assessment of quality of life and consequently the lack of robust data. Additionally, uncertainties were highlighted regarding the estimation of mortality rates, utilities, and input costs which impacted the economic analyses.

CONCLUSIONS: Our study underscored the significant gap in clinical data to evaluate comparative effectiveness, safety, and cost-effectiveness among biologics in severe asthma. Further research is warranted to design a large, pragmatic trial comparing all available drugs to determine the clinically important differences and identify subgroups of patients who are likely to benefit from a specific biologic therapy.