Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers.

To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.

Palomäki A ，FinnGen Rheumatology Clinical Expert Group ，Palotie A ，Koskela J ，Eklund KK ，Pirinen M ，FinnGen ，Ripatti S ，Laitinen T ，Mars N ... -  《-》

RS35705950 polymorphism of MUC5B Gene: Association with Rheumatoid Arthritis and Interstitial lung disease in Tunisian Population.

Saad A ，Baccouche K ，Fodha H ，Haj Khelil A ，Fakhfakh R ，Khalifa D ，El Amri N ，Saad A ，Bouajina E ... -  《-》

A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality.

To compare mortality risks in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and patients with RA without ILD. Matched cohort study. The study was conducted in Denmark, using nationwide, prospectively collected data. Among patients with RA diagnosed between 2004 and 2016, 679 patients with RA-ILD were matched for birth year, gender and age at RA diagnosis with 11 722 patients with RA but without ILD. Mortality risks were assessed using Kaplan-Meier mortality curves, and hazard rate ratios (HRRs) for death were estimated using Cox proportional hazards regression models. The number of prevalent RA patients more than doubled from 15 352 to 35 362 individuals during the study period. RA-ILD was seen in 2.2% of incident RA patients. 34.0% of RA-ILD cases were diagnosed within 1 year prior to and 1 year after the RA diagnosis. One-year mortality was 13.9% (95% CI, 11.4% to 16.7%) in RA-ILD and 3.8% (95% CI, 3.5% to 4.2%) in non-ILD RA, 5-year mortality was 39.0% (34.4% to 43.5%) and 18.2% (17.3% to 19.1%) and 10-year mortality was 60.1% (52.9% to 66.5%) and 34.5% (32.8% to 36.1%), respectively. The HRRs for death were 2 to 10 times increased for RA-ILD compared with non-ILD RA, irrespective of follow-up period. Stratified analysis showed that the HRR for death was highest in the first months after the diagnosis of RA-ILD was made, especially in patients diagnosed with RA before diagnosis of ILD. HRR was higher in males and in patients without comorbidity as assessed by the Charlson Comorbidity Index. ILD is a serious complication in RA, with a significantly increased mortality compared with a large matched cohort of RA comparisons without ILD.

Hyldgaard C ，Hilberg O ，Pedersen AB ，Ulrichsen SP ，Løkke A ，Bendstrup E ，Ellingsen T ... -  《-》

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 ... -  《-》

Effectiveness and tolerability of antifibrotics in rheumatoid arthritis-associated interstitial lung disease.

Juge PA ，Hayashi K ，McDermott GC ，Vanni KMM ，Kowalski E ，Qian G ，Bade K ，Saavedra A ，Dieudé P ，Dellaripa PF ，Doyle TJ ，Sparks JA ... -  《-》