Nintedanib in rheumatoid arthritis related interstitial lung disease: real-world safety profile and risk of side effects and discontinuation

Objective: Some concerns remain about the safety of nintedanib in patients with interstitial lung disease (ILD) related to rheumatoid arthritis (RA-ILD), such as in presence of comorbidities or in combination with biologic, targeted synthetic and/or conventional synthetic disease modifying antirheumatic drugs (DMARDs). In this multicentre study, we retrospectively evaluated the safety of nintedanib in a real-world population of RA-ILD patients from Italian GISEA registry and the possible role of comorbidities and DMARDs on drug safety and withdrawal. Secondary aim was to investigate the causes of nintedanib discontinuation. Methods: Sixty-five patients treated with nintedanib according to the current therapeutic indications were enrolled in the study. Nintedanib was prescribed in combination with DMARDs and/or steroids in 62 patients (95.4%). Results: Twelve-month retention rate of nintedanib was 76.7% and the drug was effective on about 80% of patients with at least 6 months of follow-up. Adverse events were recorded in 36 subjects (55.3%), mainly gastroenteric. Thirty-one subjects required a reduction of the nintedanib dose; among them, a transient or permanent reduction of the daily dose of nintedanib allowed to continue the treatment in 22, while 15 (23.1%) withdrew the drug, in all cases for treatment-related adverse events. Comorbidities were significantly associated to side effects at multivariate analysis, while adverse events of nintedanib were the main cause of discontinuation. Conclusion: Combination therapy with DMARDs didn't reduce safety and effectiveness of nintedanib, while adverse events were the main cause of drug withdrawal or reduction of the dose of drug, mainly due to comorbidities.