Tolerability and Safety of Nintedanib and Immunosuppression in Autoimmune Inflammatory Myopathy-Associated Progressive Pulmonary Fibrosis.

Background: Autoimmune-inflammatory myopathy-related interstitial lung diseases (AIM-ILDs) are often progressive and fibrotic. Given their rarity, little is known about the safety and tolerability of antifibrotic nintedanib in combination with immunosuppression in AIM-ILD. Research Question: Is the addition of nintedanib to immunosuppression safe and tolerable in patients with AIM-ILD, and does nintedanib administration induce peripheral blood cell gene expression changes? Study Design and Methods: This was a single-arm, open-label trial to assess safety and tolerability of nintedanib with immunosuppression. Patients with progressive, fibrotic AIM-ILD on background immunosuppression were given nintedanib for 24 weeks. The primary end point was the percentage of patients who took ≥ 90% study drug doses. The secondary end points included safety (adverse events) and efficacy (lung function) outcomes. Bulk RNA sequencing of peripheral blood was performed at baseline and each subsequent visit to examine gene expression. Results: A total of 11 participants were enrolled; of these, 9 completed the study visits as per protocol. The trial was discontinued due to slow recruitment. Three participants (27%) took ≥ 90% doses of nintedanib. Drug compliance ranged from 27% to 95%. The most common adverse events were diarrhea, nausea/vomiting, and abdominal pain. There were no overall significant changes in lung function, or difference in gene expression in peripheral blood over time identified. Interpretation: Tolerability of combined nintedanib and immunosuppression in AIM-ILD appears challenging. Nintedanib treatment did not induce measurable gene expression changes in peripheral blood. However, the study's small sample size, compounded by recruitment difficulties leading to early discontinuation, restricts the robustness and generalizability of the findings. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT05335278; URL: www.clinicaltrials.gov.