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.

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Prädiktoren für Progression und Mortalität bei Patienten mit RA-assoziierter ILD

Karger Kompass Pneumologie ◽

10.1159/000518288 ◽

2021 ◽

pp. 1-3

Author(s):

Nicolas Carlos Kahn

Keyword(s):

Carbon Monoxide ◽

Lung Function ◽

Lung Disease ◽

Pulmonary Function Tests ◽

Diffusing Capacity ◽

Radiological Progression ◽

Cox Regression Analysis ◽

Factors Associated ◽

Disease Modifying

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.

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Prädiktoren für Progression und Mortalität bei Patienten mit RA-assoziierter ILD

Karger Kompass Autoimmun ◽

10.1159/000518343 ◽

2021 ◽

pp. 1-3

Author(s):

Nicolas Carlos Kahn

Keyword(s):

Carbon Monoxide ◽

Lung Function ◽

Lung Disease ◽

Pulmonary Function Tests ◽

Diffusing Capacity ◽

Radiological Progression ◽

Cox Regression Analysis ◽

Factors Associated ◽

Disease Modifying

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Non–anti-TNF biologic agents not associated with a worsening of lung disease secondary to rheumatoid arthritis.

10.21203/rs.3.rs-18463/v1 ◽

2020 ◽

Author(s):

Natalia Mena Vázquez ◽

Francisco Javier Godoy-Navarrete ◽

Sara Manrique-Arija ◽

Maria Carmen Aguilar-Hurtado ◽

Carmen María Romero-Barco ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Lung Function ◽

Lung Disease ◽

Pulmonary Function Tests ◽

Inflammatory Activity ◽

Joint Disease ◽

High Resolution Computed Tomography ◽

Factors Associated ◽

Multicenter Prospective Observational Study

Abstract 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 change 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.

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POS0645 RITUXIMAB THERAPY IN THE INTERSTITIAL LUNG DISEASE OF RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4192 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 560.3-561

Author(s):

E. F. Vicente-Rabaneda ◽

J. De la Macorra ◽

J. P. Baldivieso ◽

F. Gutiérrez-Rodríguez ◽

A. García-Vadillo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Lung Function ◽

Adverse Events ◽

Lung Disease ◽

Statistical Significance ◽

Connective Tissue Diseases ◽

Case Series ◽

Original Research ◽

Case Control Studies

Background:Interstitial lung disease (ILD) is a severe manifestation of rheumatoid arthritis (RA), linked to increased mortality. There is still no consensus on the best therapeutic strategy as there aren’t yet randomized controlled trials.Objectives:To analyze the available scientific evidence on the efficacy and safety of rituximab (RTX) treatment of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA).Methods:A systematic search was carried out in PubMed until April 2020 following the PRISMA recommendations. Studies were selected according to the following inclusion criteria: (1) original research, including case series, case/control studies, cohort studies, and clinical trials; (2) population with RA and associated ILD, either monographically or together with other connective tissue diseases (CTD), provided that individualized data on patients with RA were provided; (3) patients treated with RTX; (4) objective and quantifiable results on the evolution of ILD after treatment with available data of FVC, DLCO and/or HRCT.Results:Of the 64 papers identified, 9 articles were selected. The studies showed great heterogeneity in design, both in the sample selection criteria and in the objectives of the analysis. Most were observational, retrospective (n = 6) or prospective (n = 2) studies, with only one open prospective experimental study. Those focused on RA predominated, but 3 of them also included patients with other CTDs. The mean age of the patients in the different studies ranged between 52 and 70 years, predominantly women. 40-79% had a history of smoking and were mostly positive for rheumatoid factor (83-100%) and anti-CCP (82-100%). The most frequent radiological patterns were NSIP, UIP and undefined. The outcome measures were diverse: changes in respiratory function tests (LTF) and HRCT, incidence of pulmonary dysfunction, mortality rates, effect on glucocorticoid deprivation, delay in inclusion in the lung transplant list and/or serious adverse events. The initiation of RTX was motivated by pulmonary and/or joint pathology, in patients with failure to other synthetic or biological DMARDs. A total of 393 treatment cycles were collected in 114 patients, with a mean of 3.45 cycles per patient. The RTX regimen was 2 infusions of 1g 2 weeks apart in all patients, except for 1 who received the lymphoma-like regimen. With regard to the efficacy of the treatment with RTX, improvement and especially stabilization of HRCT and LFT predominated, with numerically greater improvement for DLCO than for FVC. There was also a favorable trend in the evolution of patients treated with RTX compared to controls, although it did not reach statistical significance, and a lower risk of deterioration of lung function in patients treated with RTX versus those who had received other DMARDs. The mortality rate found at 5 years was lower than that previously described for the disease and half for the patients treated with RTX compared to those treated with anti-TNF. The adverse events described in the studies did not show additional safety alerts to those already described for RTX.Conclusion:RTX seems to be postulated as a promising therapy for patients with ILD associated with RA, showing a stabilizing effect on the lung function, with an acceptable safety profile. However, further research of higher methodological quality prospective studies is needed to confirm these favorable preliminary results.Disclosure of Interests:None declared

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AB0796 THE EVALUATION OF LUNG DIAGNOSTIC PROCEDURE AT THE ONSET OF INFLAMMATORY RHEUMATIC DISEASES WITH INTERSTITIAL LUNG DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3119 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1422.3-1423

Author(s):

T. Hoffmann ◽

P. Oelzner ◽

F. Marcus ◽

M. Förster ◽

J. Böttcher ◽

...

Keyword(s):

Carbon Monoxide ◽

Interstitial Lung Disease ◽

Lung Function ◽

Lung Disease ◽

Sensitivity And Specificity ◽

Lung Function Test ◽

Inflammatory Rheumatic Diseases ◽

X Ray ◽

Function Test ◽

Chest X Ray

Background:Interstitial lung disease (ILD) in inflammatory rheumatic diseases (IRD) is associated with increased mortality. Moreover, the lung is one of the most effected organs on IRD. Consequently, screening methods were required to the detect ILD in IRD.Objectives:The objective of the following study is to evaluate the diagnostic value of lung function test, chest x-ray and HR-CT of the lung in the detection of ILD at the onset of IRD.Methods:The study is designed as a case-control study and includes 126 patients with a newly diagnosed IRD. It was matched by gender, age and the performance of lung function test and chest x-ray. The sensitivity and specificity were verified by crosstabs and receiver operating characteristic (ROC) curve analysis. The study cohort was divided in two groups (ILD group: n = 63 and control group: n = 63). If possible, all patients received a lung function test and optional a chest x-ray. Patients with pathological findings in the screening tests (chest x-ray or reduced diffusing capacity for carbon monoxide (DLCO) < 80 %) maintained a high-resolution computer tomography (HR-CT) of the lung. Additionally, an immunological bronchioalveolar lavage was performed in the ILD group as gold standard for the detection of ILD.Results:The DLCO (< 80 %) revealed a sensitivity of 83.6 % and specificity of 45.8 % for the detection of ILD. Other examined parameter of lung function test showed no sufficient sensitivity as screening test (FVC = Forced Vital Capacity, FEV1 = Forced Expiratory Volume in 1 second, TLC = Total Lung Capacity, TLCO = Transfer factor of the Lung for carbon monoxide). Also, a combination of different parameter did not increase the sensitivity. The sensitivity and specificity of chest x-ray for the verification of ILD was 64.2 % versus 73.6 %. The combination of DLCO (< 80 %) and chest x-ray showed a sensitivity with 95.2 % and specificity with 38.7 %. The highest sensitivity (95.2 %) and specificity (77.4 %) was observed for the combination of DLCO (< 80 %) and HR-CT of the lung.Conclusion:The study highlighted that a reduced DLCO in lung function test is associated with a lung involvement in IRD. DLCO represented a potential screening parameter for lung manifestation in IRD. Especially patients with suspected vasculitis should receive an additional chest x-ray. Based on the high sensitivity of DLCO in combination with chest x-ray or HR-CT for the detection of ILD in IRD, all patients with a reduced DLCO (< 80%) should obtained an imaging of the lung.Disclosure of Interests:None declared

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THU0160 Disease modifying antirheumatic drugs in rheumatoid arthritis with interstitial lung disease: a prospective study

10.1136/annrheumdis-2017-eular.5824 ◽

2017 ◽

Author(s):

N Mena-Vazquez ◽

C Gόmez-Cano ◽

C Aguilar-Hurtado ◽

M Rojas-Giménez ◽

S Manrique-Arija ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Prospective Study ◽

Lung Disease ◽

Disease Modifying Antirheumatic Drugs ◽

Antirheumatic Drugs ◽

Disease Modifying ◽

A Prospective Study

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Effect of Biological Disease-modifying Anti-rheumatic Drugs on Airway and Interstitial Lung Disease in Patients with Rheumatoid Arthritis

Internal Medicine ◽

10.2169/internalmedicine.2226-18 ◽

2019 ◽

Vol 58 (12) ◽

pp. 1703-1712 ◽

Cited By ~ 9

Author(s):

Izumi Kurata ◽

Hiroto Tsuboi ◽

Mayu Terasaki ◽

Masaru Shimizu ◽

Hirofumi Toko ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Disease Modifying

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100. Are we Screening Appropriately for Interstitial Lung Disease in Rheumatoid Arthritis? A Study into the Use of Lung Function Tests at Predicting ILD

Rheumatology ◽

10.1093/rheumatology/kev088.100 ◽

2015 ◽

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Lung Function ◽

Lung Disease ◽

Lung Function Tests ◽

Function Tests

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The characteristics and clinical significance of mucin levels in bronchoalveolar lavage fluid of patients with interstitial lung disease

Journal of Investigative Medicine ◽

10.1136/jim-2018-000785 ◽

2018 ◽

Vol 67 (4) ◽

pp. 761-766

Author(s):

Li Wei ◽

Jing Zhao ◽

Jing Bao ◽

Yanliang Ma ◽

Ying Shang ◽

...

Keyword(s):

Lung Cancer ◽

Pleural Effusion ◽

Interstitial Lung Disease ◽

Lung Function ◽

Bronchoalveolar Lavage ◽

Lung Disease ◽

Clinical Significance ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Diffusing Capacity

To investigate the expression and clinical significance of secretory mucins in patients with interstitial lung disease (ILD). The bronchoalveolar lavage fluid (BALF) concentrations of mucins (MUCs) from 27 patients with ILD, 6 patients with lung cancer, 8 patients with pleural effusion and 9 patients with bronchiectasis were determined by ELISA. The concentration of MUC5AC was significantly increased in patients with ILD (12.84±15.02 ng/mL) compared with patients with pleural effusion (4.33±2.51 ng/mL), lung cancer (8.02±5.57 ng/mL) or bronchiectasis (6.08±2.40 ng/mL) (p<0.01). The MUC2 level (10.23±9.27 ng/mL) was significantly elevated in patients with ILD than in those with pleural effusion (6.21±3.28 ng/mL) or bronchiectasis (5.73±1.51 ng/mL) (both p<0.05). Patients with ILD (104.64±61.61 ng/mL), lung cancer (148.45±169.24 ng/mL) or bronchiectasis (123.68±63.28 ng/mL) had significantly greater IL-8 levels than in those with pleural effusion (76.46±2.16 ng/mL) (p<0.05). A significant positive correlation was detected between the MUC5AC concentration and the lymphocyte percentage in BALF of patients with ILD (r=0.504, p=0.007). Lung function tests of patients with ILD exhibited various degrees of restrictive ventilation dysfunction and reduced diffusing capacity. The MUC5AC levels in BALF were negatively correlated with forced expiratory volume in 1 second (FEV1)/forced vital capacity (r=−0.761, p=0.000), FEV1 predicted value (FEV1/pred) (r=−0.668, p=0.002), and diffusing capacity (r=−0.606, p=0.006). Secretory mucins MUC5AC, MUC2 and IL-8 were highly expressed in ILD. MUC5AC level was closely correlated with the amount of inflammatory cells in BALF and the lung function parameters.

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