Predictors of Progression and Mortality in Patients with Prevalent Rheumatoid Arthritis and Interstitial Lung Disease: A Prospective Cohort Study.

OBJECTIVES: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. PATIENTS AND METHODS: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving disease-modifying antirheumatic drugs (DMARDs) between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main endpoint was "Progression to ILD at the end of follow-up" in terms of the following outcomes: (1) improvement (i.e., improvement in forced vital capacity (FVC) ≥10% or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥15% and absence of radiological progression); (2) nonprogression (stabilization or improvement in FVC ≤10% or diffusing capacity of the lungs for carbon monoxide (DLCO) <15% and absence of radiological progression); (3) progression (worsening of FVC >10% or DLCO >15% and radiological progression); or (4) death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with the worsening of ILD. RESULTS: After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months after diagnosis of ILD. The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (hazard ratio (HR), 2.6 (95%CI, 1.0-6.7)), FVC <80% (HR, 3.8 (95%CI, 1.5-6.7)), anticitrullinated protein antibody titers (HR, 2.8 (95%CI, 1.1-6.8)), smoking (HR, 2.5 (95%CI, 1.1-6.2)), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 (95%CI, 0.2-0.8)). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%). Infection was fatal in 10/18 patients (55.5%) during follow-up. CONCLUSIONS: Lung function is stable in most patients with RA-ILD receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs), although one-third worsened or died. Identifying factors associated with worsening in RA-ILD is important for clinical management.

Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rheumatoid arthritis.

OBJECTIVES: To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution computed tomography (HRCT) PATIENTS AND METHODS: We performed a cross-sectional, observational study in patients with RA-ILD (cases) controlled with a group of RA patients without ILD (controls) paired by sex, age, and time of disease evolution. Patients were assessed using HRCT, PFT, and US. The main variables were B-line number, evaluation of the lung-US score already described, pleural irregularities, and A pattern US lost. ROC curve analysis was performed to establish the cut-off point of the US B-lines number for detecting the presence of significant RA-ILD in relation to HRCT, and logistic regression analysis was performed to identify the intercostal spaces. RESULTS: Seventy-one patients were included, 35 (49.2%) with ILD-RA and 36 (50.8%) RA controls. Regarding US score, we found that the detection of 5.5 lines in a reduced score of 8 intercostal spaces had a sensitivity = 62.2%, specificity = 91.3%, PPV = 88.4%, and NPV = 69.5%. In multivariate analysis, the intercostal spaces which showed independent association with ILD were 3rd right anterior axillary space (OR [IC 95%] 19.0 [1.3-27.5]), 8th right posterior axillary space (OR [IC 95%] 0.04 [0.0-0.6]), 8th right subscapular space (OR [IC 95%] 16.5 [1.8-45.5]), 9th right paravertebral space (OR [IC 95%] 7.11 [1.0-37.1]), and 2nd left clavicular middle space (OR [IC 95%] 21.9 [1.26-37.8]). CONCLUSIONS: Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. A 8-space reduced score showed a similar total predictive capacity than 72-space score. Key Points • Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. • The 72-space evaluation is highly sensitive, whereas a simplified score enables a more specific and faster diagnosis. • The number of B lines is correlated with DLCO, ACPA, inflammatory activity, and physical function.

Non-anti-TNF biologic agents are associated with slower worsening of interstitial lung disease secondary to rheumatoid arthritis.

OBJECTIVES: To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD). PATIENTS AND METHODS: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was changed in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD. RESULTS: After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). CONCLUSIONS: Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non-anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening. Key Points • We have performed prospectively evaluated lung and joint function in patients with RA-ILD receiving treatment with various DMARDs. • In our study, the lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. • Neither csDMARDs nor anti-TNF agents were associated with a significant risk of worsening of lung disease, whereas non-anti-TNF bDMARDs could reduce the risk of worsening of lung disease. • Smoking and poor control of joint involvement were the main factors associated with worsening of lung disease.