Clinical characteristics associated with pulmonary function decline despite sustained nintedanib therapy in systemic autoimmune rheumatic disease-related progressive pulmonary fibrosis

To identify clinical factors associated with pulmonary function decline despite sustained nintedanib treatment for ≥1 year in patients with systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) with progressive pulmonary fibrosis (PPF).

We retrospectively analyzed 69 patients from the KEIO-SARD-ILD cohort who initiated nintedanib. Among those who continued treatment for ≥1 year, patients were classified into Decliner (absolute decline in %FVC >5% at 12 months) and Stable groups, and clinical characteristics were compared. Independent predictors of %FVC decline were identified using multivariable logistic regression.

Among 69 patients who initiated nintedanib, 18 (26.1%) showed a decline in %FVC >5% at 12 months. Discontinuation of nintedanib within 12 months and a UIP pattern were independently associated with %FVC decline in the overall cohort. Among patients who continued nintedanib for ≥1 year, 8 of 51 patients (15.7%) experienced %FVC decline despite sustained treatment (Decliner group). Compared with Stable group, Decliner group had significantly lower body surface area and lower eGFR. In multivariable analysis, low body surface area and chronic kidney disease were independently associated with %FVC decline. Patients with both risk factors had a significantly higher prevalence of pulmonary function decline than those without these factors. Decliner group had worse overall survival than Stable group.

A subset of patients with SARD-ILD-related PPF experienced pulmonary function decline despite sustained nintedanib treatment. The decliner group had lower body surface area and higher prevalence of chronic kidney disease, suggesting that patients with these factors may be at increased risk of disease progression despite antifibrotic therapy.