EXPLORATORY ANALYSIS REVEALS POSITIVE CORRELATION BETWEEN C1 ESTERASE INHIBITOR AND SERUM COMPLEMENT 4 ANTIGEN LEVELS

Abstract

Introduction Low levels of C1-esterase inhibitor (C1-INH) and concomitant reduced complement 4 (C4) concentrations have been identified in patients with hereditary angioedema (HAE). C4 constitutes a promising candidate for a biomarker of disease activity. This investigation aims to determine the relationship between C1-INH functional activity levels (C1-INH[f]) and C4 antigen concentrations in patients with HAE treated with subcutaneous (SC) C1-INH, inferring significance for clinical practice. Methods C1-INH(f) and C4 antigen levels were assayed in three clinical studies (NCT01576523, NCT01912456, NCT02316353 [COMPACT Phase 2, 3 and open-label extension studies]). The relationship between these measurements was inspected in an exploratory manner. All measurements were performed at a central laboratory using validated assays and investigated with respect to time after C1-INH(SC) administration and HAE type. C4 antigen concentration over time after C1-INH(SC) administration was characterized, and the correlation with C1-INH(f) evaluated. Results C4 antigen concentration increased gradually following C1-INH(SC) administration until ∼100 hours post-administration when concentrations declined. A linear relationship was observed between C4 antigen concentrations and C1-INH(f) in patients with type I HAE, based on the Loess fit, until C1-INH(f) of ∼50%, at which point signs of saturability became apparent (example figure shown). The relationship in patients with type II HAE was not clear. Conclusions An exploratory analysis showed a linear relationship between C1-INH(f) and C4 antigen levels in patients with type I HAE, consistent with previous reports. The interplay between C1-INH(f) and C4 should be further explored to understand the potential role of C4 monitoring in treatment decision-making.