Post Hoc Analysis of Recombinant C1 Inhibitor Clinical Data Using Contemporary Endpoints for Hereditary Angioedema

Contemporary trials of medications to treat hereditary angioedema (HAE) attacks define efficacy endpoints using Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) scales; these differ from the visual analog scale (VAS) and treatment effect questionnaire (TEQ) used in legacy recombinant human C1 esterase inhibitor (rhC1-INH) studies. This post hoc analysis aimed to evaluate pooled rhC1-INH trial data, mapped to contemporary HAE clinical trial endpoints and designs.

Pooling data from three rhC1-INH trials for acute HAE attacks (NCT00225147, NCT01188564, NCT00262301), this analysis applied results from a bookmarking study to convert TEQ and VAS measurements to PGI-S and PGI-C scales. Kaplan-Meier estimates were calculated for time to complete resolution (TTCR; defined as "none" on PGI-S) and time to onset of symptom relief (TOSR; defined as "a little better" on PGI-C at ≥ 2 consecutive time points within 12 h). Log-rank tests were used to determine differences between treatment groups.

Across trials, 48 and 60 patients received rhC1-INH 50 U/kg and placebo, respectively. The most common attack locations were peripheral (47.9% and 41.7%, respectively) and abdominal (35.4% and 35.0%, respectively). Baseline attack severity was either severe or very severe in all patients. Median [95% confidence interval (CI)] TOSR was 0.75 h (0.55-1.50) with rhC1-INH and 8.00 h (3.00-8.05) with placebo (P < 0.001). Median (95% CI) TTCR was 4.50 h (3.55-5.50) with rhC1-INH and 24.00 h (16.00- > 24.00) with placebo (P < 0.001).

This post hoc analysis confirmed that rhC1-INH, compared with placebo, is associated with significantly shorter TOSR and TTCR of HAE attacks.

ClinicalTrials.gov: NCT00225147, NCT01188564, NCT00262301.