Stratifying GAP Stages by MUC5B rs35705950 T-Allele Carriage Refines Survival Prediction in IPF

Abstract

The genetic contribution to idiopathic pulmonary fibrosis (IPF) has become increasingly evident, enabling its translation into clinical practice. MUC5B rs35705950 has emerged as a promising prognostic biomarker. The gender-age-physiology (GAP)-model is regularly used for IPF survival prediction. In this retrospective real-world study, GAP-stages were stratified by MUC5B T-allele carriage. European patients with IPF were included in a discovery (n = 663), and replication (n = 738) cohort. The GAP+MUC5B-model was significantly more accurate compared to the GAP-model (all cohorts p < 0.001), with a modest improvement in discrimination (ΔC = 0.023; C = 0.685, 95%CI 0.665-0.704). Within each GAP-stage, T-allele carriers had significantly better median transplant-free survival outcomes than non-carriers (p < 0.001): In the combined cohort (n = 1401) survival for GAP-stage I T carriers was 70 months (m) vs 48m for T non-carriers; stage II T vs non-T: 41 vs 31m; stage III T vs non-T: 23 vs 12m. Addition of MUC5B rs35705950 T-carriership enhances GAP-based prognostication and aids clinical decision-making.