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<p>The genetic contribution to idiopathic pulmonary fibrosis (IPF) has become increasingly evident, enabling its translation into clinical practice. <i>MUC5B</i> 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 <i>MUC5B</i> 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 &lt; 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 &lt; 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 <i>MUC5B</i> rs35705950 T-carriership enhances GAP-based prognostication and aids clinical decision-making.</p>

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

  • 期刊论文

  • 发表日期：

    2025年7月30日

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  • Joanne J. van der Vis,
  • Antje Prasse,
  • Elisabetta A. Renzoni,
  • Carmel J. W. Stock,
  • Toby M. Maher,
  • Francesco Bonella,
  • Raphael Borie,
  • Bruno Crestani,
  • Wim A. Wuyts,
  • Philip L. Molyneaux,
  • Johannes C. Kelder,
  • Jan C. Grutters,
  • Coline H. M. van Moorsel

摘要

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.