scholarly journals OP0007 MUC5B PROMOTER VARIANT AND LONG-TERM INCIDENCE OF INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS: A POPULATION BIOBANK STUDY OF 250,000 INDIVIDUALS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 4.2-4
Author(s):  
A. Palomäki ◽  
T. Laitinen ◽  
J. Koskela ◽  
A. Palotie ◽  
N. Mars
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Large Scale ◽  
Strong Predictor ◽  
Risk Difference ◽  
Lifetime Risk ◽  
Large Scale Data ◽  
The Impact

Background:The promoter variant rs35705950 in MUC5B is the strongest known genetic risk factor for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) [1]. There is, however, no large-scale data on the impact of MUC5B on the long-term incidence of RA-ILD.Objectives:To describe long term risk of RA-ILD in RA patients carrying MUC5B variant compared to non-carriers with RA.Methods:FinnGen is a collection of epidemiological cohorts and hospital biobank samples, linking genotypes with up to 46 years of follow-up within nationwide registries. Diagnoses of 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. MUC5B is a common variant and has an allele frequency of 0.1 in the Finnish population.Results:Out of the 248,400 individuals, 5534 patients have been diagnosed with RA, out of whom 178 (3.2%) developed ILD. MUC5B was a strong predictor of ILD in RA patients (HR 2.14, 95%CI 1.56-2.92). In patients with RA, MUC5B conferred a lifetime risk of 14.5% (95%CI 10.7-18.1%), compared to 5.2% (4.1-6.2%) in MUC5B non-carriers with RA (Figure). In the population, MUC5B carriers and MUC5B non-carriers had lifetime risks of 3.9% and 1.3%, respectively. The risk difference started to emerge at age 65. The risk was highest in men with RA who are MUC5B carriers: 18.5% (11.1-25.2%) developed ILD, compared to 8.5% (6.1-10.9%) of MUC5B non-carriers with RA.Conclusion:We report findings from a large longitudinal study, showing that MUC5B confers a considerable lifetime risk of RA-ILD, and contributes to increased morbidity. These findings have clinical implications for improving identification of RA patients at high risk of developing ILD.References:[1]Juge P-A, Lee JS, Ebstein E, et al. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease. N Engl J Med 2018;379:2209–19Disclosure of Interests:Antti Palomäki Speakers bureau: MSD, Pfizer, Sanofi, Consultant of: Pfizer, Abbvie, Tarja Laitinen: None declared, Jukka Koskela Speakers bureau: Pfizer, Aarno Palotie: None declared, Nina Mars: None declared

scholarly journals Management of Myositis-Associated Interstitial Lung Disease

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 347
Author(s):  
Tomoyuki Fujisawa
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Current Knowledge ◽  
Strong Predictor ◽  
Calcineurin Inhibitors ◽  
Pulmonary Involvement ◽  
Trna Synthetase ◽  
Evidence Based Guidelines ◽  
Substantial Heterogeneity

Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies’ status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.

scholarly journals POS0403 RISK FACTORS FOR PROGRESSION OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE: REASSURING IMPACT OF METHOTREXATE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 431.2-431
Author(s):  
C. Lucas ◽  
A. Tremblay ◽  
S. Jouneau ◽  
A. Perdriger
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Logistic Regression ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Respiratory Function Tests ◽  
Multivariable Logistic Regression Analysis ◽  
High Resolution Computed Tomography ◽  
The Impact

Background:Factors associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression and prognosis are not well identified, especially the impact of methotrexate.Objectives:Identify risk factors of ILD progression in RA-ILD patients in a longitudinal study.Methods:RA patients with ILD confirmed in 2 high resolution computed tomography (HRCT) chest scans spaced at least 6 months apart (T0: date of the first HRCT chest scan describing ILD; Tx: date of the last HRCT chest scan available) were consecutively included in this retrospective multi-centric study from 2010 to 2020. HRCT chest scans were analyzed for each patient at T0 and Tx by 2 independent radiologists to determinate ILD pattern (definite UIP, probable UIP, indeterminate UIP, non-UIP) and progression during the follow-up including variation of the fibrosis score (aggravated or non-aggravated). Characteristics of patients (demographic-clinical-biological findings, respiratory function tests, and treatments exposure) at ILD diagnosis and during the follow-up (T0-Tx) were analyzed as potential determinants of ILD progression through multivariable logistic regression analysis. Overall survival was analyzed using Kaplan-Meier method.Results:74 RA-ILD patients were included. During a mean duration between T0-Tx of 2.8 years ± 2.4, 26 patients (35%) had ILD progression. Thirty-three patients (45%) were treated by methotrexate at ILD diagnosis (T0) and 29 of them (39%) continued methotrexate during T0-Tx. Logistic regression in multivariate analysis revealed that a treatment by methotrexate at ILD diagnosis was protective against ILD progression (OR=0.14 [0.04-0.52]; p=0.0031). Non-UIP pattern at ILD diagnosis was also protective against ILD progression (OR=0.09 [0.02-0.36]; p=0.0005). The follow-up for survival analysis was 5.1 years ± 2.9. Thirty-three patients (31%) died, and the 3-year survival rate was 80%. Survival was better for non-aggravated ILD patients (HR=3.5 [1.46-8.4]; p=0.004) and for patients treated by methotrexate during T0-Tx (HR= 0.36 [0.15-0.84]; p=0.018) and worse for definite UIP patterns (HR=2.570 [1.078-6.128]; p=0.0332).Conclusion:In RA-ILD patients, non-UIP pattern and methotrexate treatment are associated with better ILD evolution and prognosis.Disclosure of Interests:None declared

Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept

2018 ◽  
Vol 29 (3) ◽  
pp. 413-417 ◽  
Author(s):  
Takeshi Mochizuki ◽  
Katsunori Ikari ◽  
Koichiro Yano ◽  
Motoaki Sato ◽  
Ken Okazaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease

Asymptomatic Interstitial Lung Disease in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 3 (1) ◽  
pp. 69-75
Author(s):  
Khalida El-Refaei ◽  
Hend Maghraby ◽  
Hala Keshk ◽  
Bahera Fath Allah ◽  
Hala Maghraby
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease

A Perspective On The Impact of COVID-19 Pandemic in Basic Science Research and its Future implications

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Yam Nath Paudel ◽  
Efthalia Angelopoulou ◽  
Bhupendra Raj Giri ◽  
Christina Piperi ◽  
Iekhsan Othman ◽  
...  
Keyword(s):  
Basic Science ◽  
Large Scale ◽  
Preventive Measure ◽  
Science Research ◽  
Research Institutes ◽  
Basic Science Research ◽  
Long Term Consequences ◽  
Long Term Impact ◽  
The Impact

: COVID-19 has emerged as a devastating pandemic of the century that the current generations have ever experienced. The COVID-19 pandemic has infected more than 12 million people around the globe and 0.5 million people have succumbed to death. Due to the lack of effective vaccines against the COVID-19, several nations throughout the globe has imposed a lock-down as a preventive measure to lower the spread of COVID-19 infection. As a result of lock-down most of the universities and research institutes has witnessed a long pause in basic science research ever. Much has been talked about the long-term impact of COVID-19 in economy, tourism, public health, small and large-scale business of several kind. However, the long-term implication of these research lab shutdown and its impact in the basic science research has not been much focused. Herein, we provide a perspective that portrays a common problem of all the basic science researchers throughout the globe and its long-term consequences.

scholarly journals POS0210 THE INCIDENCE AND RISK FACTORS OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 322-322
Author(s):  
B. Samhouri ◽  
R. Vassallo ◽  
S. Achenbach ◽  
V. Kronzer ◽  
J. M. Davis ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cumulative Incidence ◽  
Population Based ◽  
Competing Risk ◽  
Olmsted County ◽  
Research Support ◽  
Risk Of Death

Background:Rheumatoid arthritis (RA) is a systemic inflammatory disease of the joints and other organs, including the lungs.1 Interstitial lung disease (ILD) is a lung injury pattern associated with significant symptom burden and poor outcomes in RA.2 Better understanding of its risk factors could help with disease prevention and treatment.Objectives:Using a population-based cohort, we sought to ascertain the incidence and risk factors of RA-associated ILD (RA-ILD) in recent years.Methods:The study included adult residents of Olmsted County, Minnesota with incident RA between 1999 and 2014 based on the 1987 ACR classification criteria.3 Study subjects were followed until death, migration, or 4/30/2019. ILD was defined by the presence of bilateral interstitial fibrotic changes (excluding biapical scarring) on chest computed tomography (CT). In the absence of chest CT imaging, a physician’s diagnosis of ILD in conjunction with chest X-ray findings suggestive of ILD and a restrictive pattern on pulmonary function testing (defined as a total lung capacity less than the lower limit of normal) was considered diagnostic of ILD. Evaluated risk factors included age, sex, calendar year, smoking status, body mass index (BMI) and presence/absence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Cumulative incidence of ILD was adjusted for the competing risk of death. Cox models were used to assess the association between potential risk factors and the development of RA-ILD.Results:In Olmsted County, 645 residents were diagnosed with RA between 1999 and 2014. Seventy percent of patients were females, and 30% were males; median age at RA diagnosis was 55.3 [IQR 44.1-66.6] years, and most patients (89%) were white. Fifty-three percent of patients were never-smokers, and 64% had seropositive RA. Forty percent were obese (i.e., BMI ≥30 kg/m2); median BMI was 28.3 [IQR 24.3-33.0] kg/m2.In the cohort, ILD was identified in 73 patients. The ILD diagnosis predated RA diagnosis in 22 patients (3.4%) who were excluded from subsequent analyses. Final analyses included the remaining 623 patients with no ILD preceding, or at the time of RA diagnosis. Over a median follow-up interval of 10.2 [IQR 6.5-14.3] years, 51 patients developed ILD. Cumulative incidence of ILD, adjusted for the competing risk of death, was 4.3% at 5 years; 7.8% at 10 years; 9.4% at 15 years; and 12.3% at 20 years after RA diagnosis (Figure 1).Age, and history of smoking at RA diagnosis correlated with the incidence of ILD; adjusted hazard ratios (HRs) were 1.89 per 10-year increase in age (95% confidence interval 1.52-2.34) and 1.94 (95% confidence interval 1.10-3.42), respectively. On the other hand, sex (HR: 1.21; 95% CI: 0.68-2.17), BMI (HR: 0.99; 95% CI: 0.95-1.04), obesity (HR: 0.89; 95% CI: 0.50-1.58), and seropositivity (HR: 1.15; 95% CI: 0.65-2.03) did not demonstrate significant associations with ILD.Conclusion:This study provides a contemporary estimate of the occurrence of ILD in a well-characterized population-based cohort of patients with RA. Our findings of a lack of association between sex, obesity and seropositivity with ILD may indicate a change in established risk factors for ILD and warrant further investigation.References:[1]Shaw M, Collins BF, Ho LA, Raghu G. Rheumatoid arthritis-associated lung disease. Eur Respir Rev. 2015;24(135):1-16. doi:10.1183/09059180.00008014[2]Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis - A population-based study. Arthritis Rheum. 2010;62(6):1583-1591. doi:10.1002/art.27405[3]Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. doi:10.1002/art.27584Figure 1.Cumulative incidence of ILD in patients diagnosed with RA between 1999 and 2014, adjusted for the competing risk of death. Abbreviations. ILD: interstitial lung disease; RA: rheumatoid arthritis.Disclosure of Interests:Bilal Samhouri: None declared, Robert Vassallo Grant/research support from: Research grants from Pfizer, Sun Pharmaceuticals and Bristol Myers Squibb, Sara Achenbach: None declared, Vanessa Kronzer: None declared, John M Davis III Grant/research support from: Research grant from Pfizer., Elena Myasoedova: None declared, Cynthia S. Crowson: None declared

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