A75-25 Immunosuppression in Interstitial Lung Disease: A Multi-center Clone-censor-weighting Analysis

Rationale Immunosuppression is routinely used as first-line therapy in non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs), despite limited randomized controlled trial evidence and unclear impact on long-term outcomes. Objectives To evaluate whether immunosuppressive therapy with mycophenolate or azathioprine improves three-year transplant-free survival and lung function trajectory in non-IPF idiopathic interstitial pneumonia, fibrotic hypersensitivity pneumonitis, and connective-tissue disease-associated ILD. Methods We employed a clone-censor-weighting (CCW) framework in this multi-center retrospective study to emulate a randomized controlled trial. Each patient was cloned and assigned to immunosuppression initiation within 6 months of enrollment or no initiation strategies, and censored when the assigned strategy deviated from observed treatment. Stabilized inverse probability treatment and censoring weights were used. Measurements The primary endpoint was three-year transplant-free survival assessed with weighted Cox models across treatment strategies. Weighted generalized estimating equations were used to model lung function trajectory. Main Results Among 2,207 eligible patients, 18% (186/1022) with non-IPF idiopathic interstitial pneumonia, 30% (162/544) with fibrotic hypersensitivity pneumonitis, and 31% (221/704) with connective tissue disease-associated ILD were initiated on immunosuppression within 6-months. Immunosuppression was not associated with improved survival within any ILD subtype (Figure), but was associated with worse survival in non-IPF idiopathic interstitial pneumonia (HR 1.35, 95% CI 1.02-1.80) and fibrotic hypersensitivity pneumonitis (HR 1.65, 95% CI 1.11-2.44). Immunosuppression was not associated with differential lung function trajectory within any ILD subtype. Conclusions Immunosuppression initiation showed no evidence of benefit for three-year transplant-free survival or lung function trajectory, and was associated with higher mortality in select non-IPF ILD subtypes, within common non-IPF ILD subtypes. Prospective randomized controlled trials are needed to inform patient care. This abstract is funded by: NIH, Nina Ireland Program for Lung Health, Asthma and Lung UK