scholarly journals Interstitial Lung Disease in a Woman with Rheumatoid Arthritis Treated with Denosumab: A Case Report

Author(s):  
Yu Mori ◽  
Takuya Izumiyama ◽  
Naoko Mori ◽  
Toshimi Aizawa

Abstract The present report describes the case of an 84-year-old female Japanese patient with rheumatoid arthritis (RA) who experienced exacerbation of interstitial lung disease (ILD) after denosumab (Dmab) treatment. The onset of RA occurred in 2008, and the patient had been treated with intravenous or subcutaneous injection of tocilizumab (TCZ) since 2009. In July 2013, she experienced a lumbar vertebral fracture and began treatment with 60-mg Dmab injection every 6 months in January 2014. The patient had a history of mild ILD and was evaluated for ILD by chest computed tomography (CT) imaging prior to the start of Dmab use. The vertebral fracture did not recur after the initiation of Dmab treatment, and her osteoporosis was successfully treated. However, she expressed a concern of exacerbations of cough and respiratory discomfort that had occurred since September 2019. The chest CT image in November 2015 showed minor ILD progression, whereas the image in September 2019 showed severe exacerbation of ILD. To treat this exacerbation, 10 mg of methylprednisolone (mPSL) and 2.5 mg of tacrolimus (TAC) were administered, and Dmab was discontinued. The patient was subsequently switched to oral bisphosphonate. The patient’s respiratory discomfort and the finding of interstitial lung lesion in CT imaging improved after Dmab discontinuation. This case showed that exacerbation of ILD may occur after Dmab treatment, and physicians should consider the risks of Dmab-related ILD in patients with RA complicated by ILD.

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


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.


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


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 982.2-982
Author(s):  
C. Aguilera Cros ◽  
M. Gomez Vargas ◽  
R. J. Gil Velez ◽  
J. A. Rodriguez Portal

Background:There is no specific treatment for interstitial lung disease (ILD) secondary to Rheumatoid Arthritis (RA) other than the treatment of RA without extra-articular involvement. Current regimens usually include corticosteroid therapy with or without immunosuppressants (IS), there is no consensus for the treatment.Objectives:To analyze the different treatment regimens in a cohort of patients with ILD and RA in our clinical practice.Methods:Descriptive study of 57 patients treated in our Hospital (1/1/2018 until 12/31/2019) with a diagnosis of RA (ACR 2010 criteria) and secondary ILD.The most recent American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines define three HRCT (High Resolution Computed Tomography) patterns of fibrosing lung disease in the setting of idiopathic pulmonary fibrosis (IPF): definite Usual Interstitial pneumonia (UIP) (traction bronchiectasis and honeycombing), possible UIP and inconsistent with UIP. The distinction between definite UIP and possible UIP in these to the presence or absence of honeycombing. Approved by the Ethics Committee.Quantitative variables are expressed as mean (SD) and dichotomous variables as percentages (%). Statistical analysis with SPSS version 21.Results:21 men and 36 women were included, with a mean age of 69 ± 10 years (mean ± SD), history of smoking (smokers 14%, non-smokers 43%, former smokers 42%). Clinical ILD at diagnosis (dyspnea 61%, dry cough 56%, crackling 70%, acropachy 7%). 84% were positive rheumatoid factor and 70% positive anticitrullinated protein antibody.Diagnosis of ILD by HRCT in 100% of patients with different patterns: defined UIP 26 (45%), probable UIP 2 (3%) and not UIP 29 (50%). The diagnosis of ILD was confirmed by biopsy in 12 patients.79% underwent (T) treatment prior to the diagnosis of ILD with glucocorticoids and disease-modifying drugs (DMARD). Among the traditional DMARDs used were: Methotrexate 68% (there were no cases of MTX pneumonitis), Leflunomide 47%, Hydroxychloroquine 26% and Sulfasalazine 21%. Biological therapy in 15 patients: Etanercept 19%, Adalimumab 5%, Infliximab 3% and Certolizumab 2%. Two patients presented an exacerbation and rapid progression of the ILD during the T with Etanercept with the final result of death.T with IS after the diagnosis of ILD in 80% of patients (Azathioprine 15, Rituximab 14, Abatacept 10, Tocilizumab 4, Sarilumab 1, Mofetil mycophenolate 1 and Cyclophosphamide 1).Two patients with defined UIP perform T with antifibrotic: 1st Nintedanib (INBUILD Trial, This article was published on September 29, 2019, at NEJM.org) 2nd Pirfenidone (initial diagnosis of IPF Idiopathic Pulmonary Fibrosis and subsequent of seropositive RA with UIP). Both improved greater than 10% in forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) in the 6 months after onset of T.Conclusion:Our results, in general, agree with what is published in the literature. Prospective, multicentre and larger sample studies are necessary to better define which patients would benefit more from IS T or antifibrotic T (or if the antifibrotic should be added to the previous IS).Disclosure of Interests:None declared


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