Background: The available data on the impact of JAK inhibitors (JAKi) on rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are currently limited.

Objectives: This study aimed to examine the progression of RA-ILD in France among individuals treated with JAKi, utilizing the MAJIK-SFR registry.

Methods: A prospective national multicenter observational study was conducted, identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were specifically collected from centers with at least one RA-ILD patient on JAKi, using a dedicated form. Data were gathered at JAKi initiation and follow-up visits (6, 12, and an average of 21 months post-inclusion), including chest high-resolution computed tomography (HRCT), pulmonary function tests (FVC and DLCO), acute exacerbations of ILD, respiratory infections, and lung cancers.

Results: We enrolled 42 patients with RA-ILD initiating JAKi (18 baricitinib, 11 upadacitinib, 9 tofacitinib and 4 filgotinib). Patients (26 women, 62%) were aged 61±12 and had a disease duration of 16±10 years. 15 (35%) were active smokers, 37 (88%) had positive rheumatoid factors, 39 (95%) positive ACPAs and 29 (69%) bone erosions. Mean DAS28-CRP at JAKi initiation was 4.69±1.61. 41 patients were on csDMARDs, including 37 (88%) on methotrexate, and the mean number of prior targeted therapies was 3±2. Nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. The study observed no significant changes in FVC and DLCO during follow-up (FVC (L)/LDCO (%): 3.2 L/65% at inclusion; 3.12 L/63% at 12 months follow-up and 3.03 L/60% at end of follow-up). Chest HRCT lesions remained stable in 62% of patients. Regression of chest HRCT lesions (2 NSIP and one organized lung disease) was observed in 3 patients (7%), associated with an improvement of more than 5% in the initial FVC value at the last assessment. Progressive ILD was identified during follow-up in 8 patients (including 3 NSIP and 3 UIP) receiving JAKi (19%), defined by a progressive worsening of FVC by more than 5% during follow-up and worsening of ILD lesions on chest HRCT or of their respiratory symptoms. Three were treated with Nintedanib for fibrosis. This pulmonary progression contrasted with joint efficacy, with a decrease in median DAS28-CRP from 4.29 to 2.30 (p<0.001). Cox proportional hazards analyses identified higher age at diagnosis of ILD, active smoking and the presence of extra-articular involvement as predictive factors for progression of RA-ILD. With regard to pulmonary tolerance, 5 infectious pneumonia and one pulmonary tuberculosis were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed during the 21-month follow-up period. No deaths occurred. JAKi was discontinued in 17 patients, 8 for joint inefficacy and 4 for intolerance. No discontinuation of JAKi was linked to a progression of ILD.

Conclusion: The analysis indicates a neutral effect of JAKi on RA-ILD, contrasting with notable joint efficacy. JAKi demonstrated an expected safety profile, with no increased risk of acute exacerbation of ILD in this population.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Jérôme Avouac Abbvie, Lilly, Pfizer, Galapagos, Abbvie, Galapagos, Galapagos, Felicien Triboulet: None declared, Pierre-Antoine Juge: None declared, Marie-Elise Truchetet: None declared, Thao Pham: None declared, Nicolas Roux: None declared, René-Marc Flipo: None declared, Charles Leské: None declared, Christian Roux: None declared, Raphaèle Seror: None declared, André Basch: None declared, Olilvier Brocq: None declared, Pascal Chazerain: None declared, Fabienne Coury-Lucas: None declared, Richard DAMADE: None declared, Emmanuelle Dernis: None declared, Jacques-Eric Gottenberg: None declared, André Ramon: None declared, Adeline Ruyssen-Witrand: None declared, Jean-Hugues Salmon: None declared, Emilie SHIPLEY: None declared, Anne Tournadre: None declared, Clément Prati: None declared, Philippe Dieudé: None declared.