Comparative Data on Long-Term Efficacy of Biologics in Moderate-to-Severe AD: An Expert Perspective on Using Indirect Comparison Methodology

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin condition that often requires long-term therapy for effective management. Several biologics have been approved for treating patients with moderate-to-severe AD, but, to date, no head-to-head trials comparing these biologics have been completed. Although long-term data from individual trials have been published, the differences in trial design prevent direct comparisons across treatments and therefore only indirect comparisons, such as matching-adjusted indirect comparisons (MAICs), should be used to compare efficacy endpoints. MAICs utilize individual patient data from one trial, adjusted to match the summary statistics for relevant demographic and disease characteristics with those of an aggregate comparator trial. METHODS: Available published phase 3 clinical trial data on the long-term efficacy of approved biologics for the treatment of moderate-to-severe AD were reviewed to provide an overview of the key differences in trial design for AD biologics, and the implications of these differences for comparing efficacy. Available published MAIC analyses of clinical trial data were reviewed to provide further insights into the long-term efficacy of approved biologics for the treatment of moderate-to-severe AD. RESULTS: Six long-term combination therapy and monotherapy trials were summarized and assessed, revealing substantial differences in trial design that prevent efficacy comparisons of AD biologics. Three available MAIC analyses comparing trials of biologics for AD were reviewed and critically assessed, revealing important considerations for robust MAIC analyses and highlighting the limitations and advantages of MAIC analyses in the absence of head-to-head trial data. CONCLUSION: Although any interpretation of indirect treatment comparisons should be made with caution, anchored MAIC remains a valuable and methodologically appropriate tool for comparative assessment when direct head-to-head evidence is unavailable. Available MAIC analyses indicate comparable long-term efficacy among three widely-used biologics-tralokinumab, dupilumab, and lebrikizumab-in the treatment of moderate-to-severe AD.