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

Introduction: Autoimmune-inflammatory myopathy related interstitial lung disease (AIM-ILD) are often progressive and fibrotic. Given the rarity of this disease, little is known about the safety and tolerability of nintedanib, an anti-fibrotic treatment, in combination with immunosuppression in this population. The objective of this single-arm, open-label trial was to assess safety and tolerability of nintedanib in AIM-ILD, and to determine if peripheral blood cell gene expression changes with administration of nintedanib. Methods: Patients with progressive, fibrotic AIM-ILD on background immunosuppression enrolled in this trial were given nintedanib for 24 weeks. Primary endpoint was the percentage of subjects who took 90% or more of the study drug doses. Secondary endpoints included safety (adverse events) and efficacy (lung function) outcomes. Bulk RNA sequencing of peripheral blood was performed at baseline and each subsequent visits to examine gene expression. Results: Eleven participants were enrolled, of which nine completed the study visits as per protocol at 24 weeks. The trial was discontinued due to slow recruitment. Only 3 (27%) participants took 90% or more 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 significant changes in lung function over time. No difference in gene expression over time was identified. Conclusions: Our trial was limited by small sample size and challenging recruitment, making clear conclusions on safety and tolerability difficult. The nintedanib treatment did not induce measurable gene expression changes in peripheral blood. Based on this small population, tolerability of nintedanib with immunosuppression in AIM-ILD appears challenging.