Long-term safety and pulmonary function stabilization with nintedanib in systemic sclerosis-associated interstitial lung disease, 2020–2025: a real-world retrospective study from a reference centre

Randomized trials have demonstrated that nintedanib is beneficial for Systemic Sclerosis-associated interstitial lung disease (SSc-ILD) with an acceptable safety profile. We evaluated the long-term safety and efficacy of nintedanib in a real-world SSc-ILD cohort. Medical records of SSc patients receiving nintedanib for newly diagnosed fibrotic or progressive ILD between 2020 and 2025 in our center were retrospectively reviewed. Forced vital capacity (FVC%) and diffusing capacity for carbon monoxide (DLCO%), were recorded 12 months before and 12/24/36 months after nintedanib initiation and compared by Wilcoxon signed-rank test. Safety analyses included all treated patients; efficacy analyses excluded patients initiating immunosuppression simultaneously with nintedanib. Fifty-one patients (41 female; 34 diffuse SSc; median age and disease duration of 53 and 6 years, respectively) received nintedanib for a median of 33 months (range 4-60). Diarrhea was the most frequent adverse event leading to dosage reduction in 31% and permanent discontinuation in 14% of patients, respectively. No additional safety signals emerged in patients receiving mycophenolate (n = 18), tocilizumab (n = 14), rituximab (n = 1), mycophenolate plus tocilizumab (n = 5) or mycophenolate plus rituximab (n = 2). FVC% and DLCO%, that had declined significantly during the preceding year, remained stable after nintedanib initiation in 23/35 patients with median FVC changes of + 1% and - 3% and median DLCO% changes of -2% and - 4% after 24 and 36 months, respectively), including patients on reduced dosage. Real-world data show that nintedanib seems to stabilize pulmonary function in progressive SSc-ILD, even at reduced doses, during 3 years of follow-up in about half of patients, without safety concerns when combined with biologic agents.