Real-world evidence of the antifibrotic nintedanib in rheumatoid arthritis-interstitial lung disease. National multicenter study of 74 patients

Objective: To assess the effectiveness and safety of the antifibrotic drug nintedanib in rheumatoid arthritis (RA)- related interstitial lung disease (ILD) and a progressive phenotype in clinical practice. Methods: National Spanish multicenter study of RA-ILD patients to whom nintedanib was added due to progressive fibrosing ILD. Outcome variables were effectiveness, retention rate and safety. Forced vital capacity (FVC) evolution was the primary endpoint. A comparative study between our cohort and those RA-ILD patients included in the INBUILD trial (n = 89, 42 treated with nintedanib) was performed. Results: A total of 74 patients (31 women/43 men) were collected, mean age of 69.3 +/- 8.8 years. Median [IQR] ILD duration up to antifibrotic initiation was 51 [22-77.5] months. Besides corticosteroids (n = 54), nintedanib was used combined with cDMARD (n = 21), bDMARD (n = 46) and/or JAKi (n = 4) and monotherapy (n = 3). Mean FVC one year before nintedanib start was 81.9 +/- 21.2 (% pred.), whilst mean baseline FVC was 73.7 +/- 22.5 (% pred.). After a median follow-up of 15 [10-22, 4-9] months, no significant decline in mean FVC or DLCO values was observed. Moreover, the evolution of DLCO and FVC significantly differed from a predictive model that assumed their changes without the drug. The retention rate with nintedanib was 78.4 %. During the follow up, 16.7 % of patients showed ILD progression or progressive pulmonary fibrosis. Gastrointestinal adverse events were the most common reason for nintedanib discontinuation. Compared with INBUILD trial, patients from clinical practice were older, had a higher tobacco exposure, time since ILD diagnosis was longer and treatment with combined immunosuppressants was more frequent. However, baseline mean values of FVC and DLCO were similar in both groups. Conclusion: Nintedanib seems to be effective and relatively safe in progressive fibrosing RA-ILD despite clinical differences with the INBUILD trial.