American journal of respiratory and critical care medicine · 2026
Mycophenolate and azathioprine in fibrotic interstitial lung disease.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Pugashetti Janelle Vu, Jee Adelle S, Yu Andrew R, Hammoud Noor, Chua Felix, Yazbeck Leda, Lee Cathryn T, Liu Gabrielle Y, Adams Traci N, Adegunsoye Ayodeji, Wolters Paul J, Khanna Dinesh, Strek Mary E, Oldham Justin M, Molyneaux Philip L, Newton Chad A
Аннотация
RATIONALE: Immunosuppression is routinely used for non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs), despite limited trial evidence and unclear impact on long-term outcomes.
OBJECTIVES: To evaluate whether mycophenolate or azathioprine improves 3-year transplant-free survival and lung function trajectory in fibrotic ILD, including non-IPF idiopathic interstitial pneumonia (IIP), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease (CTD)-associated ILD.
METHODS: We employed a clone-censor-weighting framework to emulate a randomized controlled trial in this multicenter retrospective study. 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 3-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 2270 included patients, 18% (186/1022) with non-IPF IIP, 30% (162/544) with fHP, and 31% (221/704) with CTD-ILD were initiated on immunosuppression within 6 months. Immunosuppression was not associated with improved survival within any ILD subtype but was associated with worse survival in non-IPF IIP (hazard ratio [HR] = 1.38; 95% CI, 1.04-1.84) and fHP (HR = 1.62; 95% CI, 1.09-2.40). Immunosuppression was not associated with differential lung function trajectory within any ILD subtype.
CONCLUSIONS: In this study, immunosuppression initiation showed no evidence of benefit for 3-year transplant-free survival or lung function and was associated with higher mortality in select fibrotic ILD subtypes. Prospective randomized controlled trials are needed to inform patient care.
OBJECTIVES: To evaluate whether mycophenolate or azathioprine improves 3-year transplant-free survival and lung function trajectory in fibrotic ILD, including non-IPF idiopathic interstitial pneumonia (IIP), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease (CTD)-associated ILD.
METHODS: We employed a clone-censor-weighting framework to emulate a randomized controlled trial in this multicenter retrospective study. 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 3-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 2270 included patients, 18% (186/1022) with non-IPF IIP, 30% (162/544) with fHP, and 31% (221/704) with CTD-ILD were initiated on immunosuppression within 6 months. Immunosuppression was not associated with improved survival within any ILD subtype but was associated with worse survival in non-IPF IIP (hazard ratio [HR] = 1.38; 95% CI, 1.04-1.84) and fHP (HR = 1.62; 95% CI, 1.09-2.40). Immunosuppression was not associated with differential lung function trajectory within any ILD subtype.
CONCLUSIONS: In this study, immunosuppression initiation showed no evidence of benefit for 3-year transplant-free survival or lung function and was associated with higher mortality in select fibrotic ILD subtypes. Prospective randomized controlled trials are needed to inform patient care.