OBJECTIVES: In the absence of head-to-head trials, indirect treatment comparisons (ITC) are a valuable source of evidence to understand comparative efficacy and inform decision making. However, they must account for differences across trials to prevent biased results. This study assesses the feasibility of conducting an ITC to obtain unbiased estimates of the relative efficacy of biologics for treatment of uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP).

METHODS: A systematic literature review, conducted in April 2021 in accordance with PRISMA guidelines, identified trials reporting on the efficacy of biologics. Trial study design, participant population, treatment implementation, outcome measures, and analysis methods were compared. Differences that could potentially bias results from a traditional anchored ITC were further assessed to determine if an anchored population-adjusted ITC (PAIC) could account for the imbalances.

RESULTS: 5 phase 3 RCTs were included (SYNAPSE [mepolizumab], SINUS 24/52 [dupilumab], POLYP 1/2 [omalizumab]) and all had placebo as the comparator. Cross-trial differences were observed in regard to gender, proportion with asthma, proportion with AERDs, disease history (number and recency of prior surgery, prior SCS use, prior intranasal corticosteroid use [INCS]), and disease severity at baseline (VAS symptom score, SNOT-22, and NPS), which may bias traditional anchored ITC results. While a PAIC could account for many differences, it cannot account for cross-trial differences in INCS use requirements prior to screening or imbalances in important disease characteristics (nasal obstruction/congestion and sense of smell) that were assessed with different tools across the trials. Further, there were different statistical approaches (e.g. handling SCS use as intercurrent events across the trials), which an ITC cannot adjust for.

CONCLUSIONS: Due to differences in the distribution or lack of consistent measurement of important treatment effect-modifying variables, it is challenging to conduct comparative efficacy analyses with a traditional ITC or an anchored PAIC.