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PRO7 A NETWORK META-ANALYSIS COMPARING C1 AND KALLIKREIN INHIBITORS APPROVED FOR PROPHYLAXIS OF HEREDITARY ANGIOEDEMA IN THE UNITED STATES

      Objectives

      Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder caused mostly due to deficient (Type-1) or dysfunctional (Type-2) C1 esterase inhibitors (C1INHs). There is lack of head-to-head randomized controlled trials (RCTs) among intravenous plasma-derived C1INH (pdC1INH-IV), subcutaneous pdC1INH (pdC1INH-SC), and kallikrein inhibitor (lanadelumab) – three most recent prophylactic HAE treatments approved in the United States (US). This study attempts to synthesize a network meta-analysis (NMA) and assess comparative efficacy of these prophylactic treatments in HAE Type-1 and Type-2.

      Methods

      A targeted literature review was conducted in January 2019 using Ovid platform for English language publications in MEDLINE, Embase, and Cochrane Library on pdC1INH-IV, pdC1INH-SC, and lanadelumab. NMA was conducted using WinBUGS v1.4.

      Results

      Literature review identified three key placebo-controlled RCTs, pooling 237 patients for NMA. Considering variability in study design, outcome definitions, and population across RCTs, five dosages of pdC1INH-SC and lanadelumab were assessed in base case NMA, while two doses of pdC1INH-IV were considered for sensitivity analysis. Fixed effects model base case results showed significantly lower mean normalized attacks per month with pdC1INH-SC 60IU (absolute difference [AD]: 3.512; 95% credible intervals [CrI]: 2.762-4.262), pdC1INH-SC 40IU (AD: 2.435; 95% CrI: 1.536-3.360), lanadelumab 150mg q4w (AD: 1.489; 95% CrI: 1.075-1.903), lanadelumab 300mg q4w (AD: 1.439; 95% CrI: 1.035-1.842), and lanadelumab 300mg q2w (AD: 1.709; 95% CrI: 1.320-2.091) compared to placebo. Mean rescue medication use per month was also significantly lower for pdC1INH-SC 60IU (AD: 3.572; 95% CrI: 2.646-4.507), pdC1INH-SC 40IU (AD: 4.732; 95% CrI: 1.046-8.531), lanadelumab 150mg q4w (AD: 1.328; 95% CrI: 0.9501-1.705), lanadelumab 300mg q4w (AD: 1.217; 95% CrI: 0.841-1.594), and lanadelumab 300mg q2w (AD: 1.428; 95% CrI: 1.067-1.786) compared to placebo.

      Conclusions

      This NMA presents the first comparative efficacy results for prophylactic HAE treatments. Wide heterogeneity in evidence warrants more robust RCT designs investigating long-term treatments for HAE.