Evaluation of rheumatoid arthritis-associated interstitial lung disease in patients treated with JAK inhibitors: a MAJIK-SFR cohort study.

To examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry. Prospective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers. We enrolled 42 patients (26 women, 62%) with RA-ILD with a mean age of 61±13 years and a mean disease duration of 16±10 years. Compared with the 778 RA patients without ILD from the MAJIK registry, RA-ILD patients were older, displayed more severe and active disease and had more prevalent comorbidities. Non-specific interstitial pneumonia and usual interstitial pneumonia accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. No significant changes in FVC and DLCO were observed during the follow-up period. Chest HRCT lesions remained stable in 69% of patients. Progressive ILD was identified in 8 patients (19%). 16 (38%) respiratory tract infections were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed. No deaths occurred. JAKi was discontinued in 17 patients including 8 for inefficacy on joint involvement and 5 for intolerance. The analysis indicates stability of RA-ILD in patients treated with JAKi. The tolerance profile of JAKi in this higher risk population did not reveal new safety signal.

Triboulet F ，Juge PA ，Truchetet ME ，Pham T ，Roux N ，Flipo RM ，Leské C ，Roux CH ，Seror R ，Basch A ，Brocq O ，Chazerain P ，Coury-Lucas F ，Damade R ，Dernis E ，Gottenberg JE ，Ramon A ，Ruyssen-Witrand A ，Salmon JH ，Shipley É ，Tournadre A ，Prati C ，Dieudé P ，Avouac J ... -  《-》

Impact of Janus kinase inhibitors and methotrexate on interstitial lung disease in rheumatoid arthritis patients.

Little is known about how various treatments impact the progression of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Here, we compared ILD progression in RA patients treated with Janus kinase inhibitors (JAKi) or biological disease-modifying anti-rheumatic drugs (bDMARDs). In vitro experiments were also performed to evaluate the potential effects of the drugs on epithelial-mesenchymal transition (EMT), a key event in pulmonary fibrosis. This retrospective study included 93 RA-ILD patients who initiated treatment with JAKi, tumour necrosis factor inhibitors (TNFi), or abatacept between 2017 and 2020. Worsening ILD was quantified by changes in chest computed tomography (CT) scans between baseline and follow-up (mean 14 months, range 6-51 months). Response to treatment was evaluated using Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Expression of the EMT marker N-cadherin in A549 lung cells was assessed by western blotting. Worsening ILD was detected in 19.4% (7/36), 16.7% (5/30), and 22.2% (6/27) of patients treated with JAKi, abatacept, and TNFi, respectively. Multivariate analysis identified female gender (P=0.043) and >10% fibrotic lesions (P=0.015) as significant predictors of worsening ILD. DAS28-ESR-based non-responder status was also significantly associated with worsening ILD (P=0.0085). In vitro, combination treatment with methotrexate and baricitinib significantly impeded EMT progression. Worsening ILD was associated with more extensive fibrotic lesions at baseline and female gender in RA patients treated with JAKi or bDMARDs. JAKi and methotrexate co-treatment may prove beneficial in modifying key events underlying the pathogenesis of RA-ILD.

Kurushima S ，Koga T ，Umeda M ，Iwamoto N ，Miyashita R ，Tokito T ，Okuno D ，Yura H ，Ishimoto H ，Kido T ，Sakamoto N ，Ueki Y ，Mukae H ，Kawakami A ... -  《Frontiers in Immunology》

Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis - a nested case-control study within the German biologics register RABBIT.

To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months. We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97-1.40] and 1.06 [0.86-1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35-2.57]) and log CRP (1.55 [1.21-1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings. Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient's global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.

Ramien R ，Rudi T ，Alten R ，Krause A ，Schneider M ，Schaefer M ，Strangfeld A ，Meissner Y ... -  《-》

Anti-mutated citrullinated vimentin antibodies as a biomarker for interstitial lung disease in patients with rheumatoid arthritis.

Elsayed SA ，Mohafez OM ，Saif DS 《-》

[Diagnostic significance of serum chemokine CXCL-10 and Krebs von den lungen-6 level in patients with rheumatoid arthritis associated interstitial lung disease].

Yan R ，Ke D ，Zhang Y ，Li L ，Su H ，Chen W ，Sun M ，Liu X ，Luo L ... -  《-》