Indirect Comparison of Lanadelumab and Intravenous C1-INH Using Data from the HELP and CHANGE Studies: Bayesian and Frequentist Analyses

BACKGROUND: Hereditary angioedema (HAE) with C1-esterase inhibitor (C1-INH) deficiency is a rare disease associated with painful, potentially fatal swelling episodes affecting subcutaneous or submucosal tissues. HAE attacks recur with unpredictable severity and frequency throughout patients’ lives; long-term prophylaxis is essential for some patients. In the absence of head-to-head studies, indirect treatment comparison (ITC) of long-term prophylactic agents is a valid approach to evaluate comparative efficacy. METHODS: We conducted an ITC using data from the placebo-controlled HELP study (assessing patients receiving lanadelumab 300 mg every 2 or 4 weeks) and the 12-week, parallel arm, crossover CHANGE study (assessing intravenous C1-INH). Outcomes of interest were attack rate ratio (ARR) and time to attack after day 0 (TTA0) and after day 70 (TTA70). Two ITC methodologies were used: a Bayesian approach using study results to update non-informative prior distributions to posterior distributions on relative treatment effects, and a frequentist approach using patient-level data from HELP and CHANGE to generate Poisson regressions (for ARR) and Cox models (for TTA0 and TT70). RESULTS: Both Bayesian and frequentist analyses suggested that lanadelumab reduced HAE attack rate by 46–73% versus intravenous C1-INH. Relative to intravenous C1-INH, risk of first attack after day 0 was comparable between intravenous C1-INH and both lanadelumab doses; risk of first attack after day 70 was reduced by 81–83% with lanadelumab 300 mg every 2 weeks, compared with C1-INH. CONCLUSIONS: Findings from these two ITC methodologies support the favorable efficacy of lanadelumab in reducing the HAE attack rate and extending attack-free intervals in patients with HAE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40268-021-00337-4.