scholarly journals Abatacept in rheumatoid arthritis-associated interstitial lung disease: short-term outcomes and predictors of progression

Author(s):  
Marika Tardella ◽  
Marco Di Carlo ◽  
Marina Carotti ◽  
Andrea Giovagnoni ◽  
Fausto Salaffi

Abstract Introduction Interstitial lung disease in rheumatoid arthritis (RA-ILD) is an extra-articular involvement that impairs the prognosis and for which there is still no well-coded treatment. The aim of this study was to evaluate abatacept (ABA) effectiveness and safety in patients with RA-ILD. Methods RA-ILD patients who started ABA treatment were consecutively enrolled. Chest high-resolution computed tomography (HRCT), clinical, laboratory and respiratory function variables were collected at baseline and after 18 months of ABA treatment. HRCT abnormalities were evaluated using a computer-aided method (CaM). ABA response was established based on the change in the percentage of fibrosis evaluated at HRCT-CaM, dividing patients into “worsened” (progression ≥ 15%), “improved” (reduction ≥ 15%), and “stable” (changes within the 15% range). The multivariate regression model was used to assess the associations between RA characteristics and ABA response. Results Forty-four patients (81% women, mean age 59.1 ± 8.0, mean disease duration of 7.5 ± 3.1 years) were studied. Five patients (11.4%) showed RA-ILD progression, 32 patients (72.6%) were considered stable, and 7 patients (16.0%) showed an RA-ILD improvement. The proportion of current smokers was significantly different between “worsened” patients, respect to those defined as "improved/stable” (p = 0.01). Current smoking habit (p = 0.005) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in multivariate regression analysis. Conclusion Treatment with ABA is associated with a RA-ILD stability or improvement in the 88.6% of patients. Current smoking habit and concomitant treatment with methotrexate are the modifiable factors associated with RA-ILD worsening. Key Points• Abatacept plays a favourable role in the control of RA-ILD, with a significant worsening in only 11.4% of patients during a 18-month follow-up period.• The predictive variables related to RA-ILD progression during abatacept therapy are the concomitant treatment with methotrexate and current smoking habit.

2020 ◽  
Author(s):  
Marco Di Carlo ◽  
Marika Tardella ◽  
Emilio Filippucci ◽  
Marina Carotti ◽  
Fausto Salaffi

Abstract Background. In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. However, in patients with RA it is not yet clear how to interpret, in quantitative terms, the presence of B-lines, the LUS artifact indicative of ILD. The aim of this study was to determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods. A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Results. 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). The presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4.Conclusion. The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.


2020 ◽  
Author(s):  
Marco Di Carlo ◽  
Marika Tardella ◽  
Emilio Filippucci ◽  
Marina Carotti ◽  
Fausto Salaffi

Abstract Background In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD. The aim of this study was to determine the cut-off number of LUS B-lines that identifies a significant RA-ILD. Methods A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence. Patients underwent LUS (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis. Results 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). The presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4. Conclusion The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.


2015 ◽  
Vol 9 (1) ◽  
pp. 0-0
Author(s):  
Бестаев ◽  
D. Bestaev ◽  
Божьева ◽  
L. Bozheva

Rheumatoid arthritis is an inflammatory rheumatic disease with unknown etiology characterized by symmetric, chronic and erosive arthritis (synovitis) of the peripheral joints and systemic inflammatory involvement of the viscera. Lung pathology, including interstitial lung disease, is one of the common extra-articular manifestations at the гheumatoid arthritis. The leading diagnosis method of interstitial lung disease is a computed tomography high resolution, which allows to identifying interstitial lung changes in 70% of the cases. The study of prognosis in patients with rheumatoid arthritis interstitial lung disease has been the subject of several studies in the past decade. In most studies it was stated that the average life expectancy from diagnosis is around 3 years. This work is devoted to study of interstitial lung disease as one of the most frequent extra-articular ma-nifestations of rheumatoid arthritis. The authors defined the significance of computed tomography high resolu-tion for the diagnosis of pulmonary interstitial lung changes at rheumatoid arthritis. They give comparative clini-cal and immunological, instrumental characteristics of rheumatoid arthritis patients with interstitial lung disease and without it. The role of smoking and positivity of anti-cyclic citrullinated peptide (anti-CCP) according to antibodies are determined as risk factors of interstitial lung disease development in patients with rheumatoid arthritis. The interrelation of the X-ray tomography symptom of interstitial lung disease "ground glass opacity" with the activity and duration of rheumatoid arthritis is revealed. "Ground glass opacity" symptom is associated with high index of DAS28 in patients with rheumatoid arthritis with interstitial lung disease.


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

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 322-322
Author(s):  
B. Samhouri ◽  
R. Vassallo ◽  
S. Achenbach ◽  
V. Kronzer ◽  
J. M. Davis ◽  
...  

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1143.2-1144
Author(s):  
J. Antony ◽  
R. Sankaralingam ◽  
R. Maheshwari ◽  
B. Chilukuri ◽  
S. Chinnadurai

Background:Rituximab (RTX) is a chimeric monoclonal antibody against CD20. There is a paucity of studies done with RTX biosimilars. This is a Retrospective and Observational study from January 2018 to December 2019 done in the Department of Clinical Immunology & Rheumatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.Objectives:1.To find the effects of varying doses of RTX in attaining clinical remission in RA.2.To find if CD19, CD20 & IgG help in identifying impending flare & if these levels help in deciding the timing of the next dose of RTX.Methods:Rheumatoid arthritis (RA) cases who were given Rituximab from January 2018 were selected. Clinical Response at 6 & 12 months & wherever feasible at 18 & 24 months was assessed by Simplified Disease Activity index (SDAI). RTX initial dose was given at 0 and 14 days followed by fixed dose at six months interval.CD19, CD20 B cell count, IgG levels were tested in patients in whom it was feasible at baseline & 6 months (select patients at 12,18 &24 months). Patients were divided in to 5 groups (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and (500mg & 1g). Patients were divided into three clinical groups, (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and two treatment groups (500mg & 1g) based on clinical indication for RTX and dose of RTX, respectively. In patients with ILD, CT scan & FVC were compared at baseline & 12 months.Results:29 patients (seropositive 28 (RF/Anti CCP/BOTH+VE), seronegative 1) were given RTX for RA over a 2-year period of which 12 had CD19, CD20 & IgG tested. Mean SDAI reduction from baseline to 6 months post treatment was 30%, 32% & 14% while complete remission (SDAI<3.3) was attained in 100%, 18% & 20% in DMARD naïve, DMARD resistant & ILD groups, respectively. CD19, CD20 & IgG reduced from 18.6%, 18.4% & 18.53g/L to 3.7%,3.7% & 9.7g/L respectively FVC improved from 62.4% to 67% at 12. The percentage of patients with lung involvement >20% reduced from 53.3% to 46.7%. Flare was observed in one patient who received 500mg RTX. CD19, CD20 & IgG levels increased from 7.9%, 8% & 9.8g/L to 27%, 25% & 13g/L respectively. 3 patients in the 1g group were followed up at 12,18 & 24 months. In these patients there were no flares or worsening symptoms. 1 patient was double negative for RF & Anti CCP and this patient did not attain clinical remission even after 2 doses of 1g RTX.Conclusion:[1]Patients with early arthritis (diagnosis made within 1 year) and who were DMARD naïve had an excellent response to Rituximab.[2]Complete remission was observed in more patients the 1g compared to 500mg group.[3]Reduction in CD19 & CD20 was associated with significant reduction in the SDAI score.[4]There was no significant reduction of CD19 & CD20 with 500mg dose of Rituximab where either a partial remission or mild flare was observed.[5]There was reduction in the lung involvement to less than 20%(CT) in few patients with 1g dose.[6]Double negative Rheumatoid arthritis poorly responded to Rituximab.[7]The positive effects of 1g Rituximab could be noted up to 24 months.[8]Flare of RA was associated with significant increase in CD19 & CD20.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 937.1-937
Author(s):  
V. Pulito-Cueto ◽  
S. Remuzgo-Martínez ◽  
F. Genre ◽  
V. M. Mora-Cuesta ◽  
D. Iturbe Fernández ◽  
...  

Background:Interstitial lung disease (ILD) is one of the most significant comorbidities of rheumatoid arthritis (RA), increasing the mortality in these patients [1,2]. Although the pathogenesis of ILD associated to RA (RA-ILD+) remains poorly defined [1], it is known that vascular tissue plays a crucial role in lung physiology [3]. In this context, a population of cells termed endothelial progenitor cells (EPC) are involved in vasculogenesis and endothelial tissue repair [4]. Previous reports suggest the implication of EPC in different conditions such as RA and idiopathic pulmonary fibrosis (IPF), the most common and destructive ILD [5,6]. Nevertheless, little is known about their specific role in RA-ILD+.Objectives:The purpose of this study was to shed light on the potential role of EPC in endothelial damage in RA-ILD+.Methods:Peripheral venous blood was collected from a total of 68 individuals (18 with RA-ILD+, 17 with RA-ILD-, 19 with IPF and 14 healthy controls). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by the expression of surface antigens by flow cytometry. The combination of antibodies against the stem cell marker CD34, the immature progenitor marker CD133, the endothelial marker VEGF receptor 2 (CD309) and the common leukocyte antigen CD45 was used. EPC were considered as CD34+, CD45Low, CD309+and CD133+. All statistical analyses were performed using Prism software 5 (GraphPad).Results:EPC frequency was significantly increased in patients with RA-ILD+, RA-ILD-and IPF compared to controls (p=0.001, p=0.002, p< 0.0001, respectively). Nevertheless, patients with RA, both RA-ILD+and RA-ILD-, showed a lower frequency of EPC than those with IPF (p= 0.048, p= 0.006, respectively).Conclusion:Our results provide evidence for a potential role of EPC as a reparative compensatory mechanism related to endothelial damage in RA-ILD+, RA-ILD-and IPF patients. Interestingly, EPC frequency may help to establish a differential diagnostic between patients with IPF and those who have an underlying autoimmune disease (RA-ILD+).References:[1] J Clin Med 2019; 8: 2038;[2] Arthritis Rheumatol 2015; 67: 28-38;[3] Nat Protoc 2015; 10: 1697-1708;[4] Science 1997; 275: 964-966;[5] Rheumatology (Oxford) 2012; 51: 1775-1784;[6] Angiogenesis 2013; 16: 147-157.Acknowledgments:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: PI18/00042 (ISCIII-ERDF); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo-Martínez: None declared, Fernanda Genre: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Sonia Fernández-Rozas: None declared, Leticia Lera-Gómez: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Belén Atienza-Mateo: None declared, Virginia Portilla: None declared, David Merino: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Alfonso Corrales Speakers bureau: Abbvie, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD


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