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

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 ◽  
...  

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

2020 ◽  
Vol 2020 ◽  
pp. 1-4 ◽  
Author(s):  
Caterina Vacchi ◽  
Andreina Manfredi ◽  
Giulia Cassone ◽  
Carlo Salvarani ◽  
Stefania Cerri ◽  
...  

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease characterized by joint and extra-articular involvement. Among them, interstitial lung disease (ILD) is one of the most common and severe extra-articular manifestations, with a negative impact on both therapeutic approach and overall prognosis. ILD can occur at any point of the natural history of RA, sometimes before the appearance of joint involvement. Since no controlled studies are available, the therapeutic approach to RA-ILD is still debated and based on empirical approaches dependent on retrospective studies and case series. Here, we report the case of a 75-year-old patient affected by RA complicated by ILD successfully treated with a combination therapy of an antifibrotic agent, nintedanib, and an inhibitor of IL-6 receptor, sarilumab. We obtained a sustained remission of the joint involvement and, simultaneously, a stabilization of the respiratory symptoms and function, with a good safety profile. To date, this is the first report describing a combination therapy with nintedanib and a disease-modifying antirheumatic drug (DMARD) for the management of RA complicated by ILD. Future prospective studies are needed to better define efficacy and safety of this approach in the treatment of these subjects.


2017 ◽  
Vol 69 (3) ◽  
pp. 542-549 ◽  
Author(s):  
Jorge A. Zamora-Legoff ◽  
Megan L. Krause ◽  
Cynthia S. Crowson ◽  
Jay H. Ryu ◽  
Eric L. Matteson

Rheumatology ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 3983-3986
Author(s):  
Javier Narváez ◽  
Vanesa Vicens-Zygmunt ◽  
Juan-José Alegre ◽  
Silvia Herrera-Lara ◽  
Joan-Miquel Nolla ◽  
...  

2021 ◽  
Vol 10 (4) ◽  
pp. 874
Author(s):  
Natalia Mena-Vázquez ◽  
Marta Rojas-Gimenez ◽  
Carmen María Romero-Barco ◽  
Sara Manrique-Arija ◽  
Espildora Francisco ◽  
...  

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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 885.2-885
Author(s):  
A. Alunno ◽  
F. Carubbi ◽  
O. Bistoni ◽  
M. Antonucci ◽  
E. Bartoloni Bocci ◽  
...  

Background:Anti-cyclic citrullinated peptide (anti-CCP) auto-antibodies represent the current gold standard for the diagnosis of rheumatoid arthritis (RA). However, growing evidence suggests that a variety of other citrullinated self-proteins may act as autoantigens and lead to the production of autoantibodies (1). Furthermore, autoantibodies believed to be RA-specific have been detected also in patients with connective tissue diseases (CTDs). We recently demonstrated that antibodies against citrullinated alpha-enolase (anti-CEP1) are a biomarker of erosive disease and RA-associated interstitial lung disease (2).Objectives:The purpose of this study was to investigate the prevalence and possible prognostic value of anti-CEP-1 in patients with CTDs.Methods:Two hundred and twelve consecutive patients with CTDs (51 systemic lupus erythematosus (SLE), 85 primary Sjogren’s syndrome (pSS) and 76 systemic sclerosis (SSc)) were studied and compared to 97 sex and age matched normal controls (NC) and 267 patients with RA. Anti-CEP1 IgG were detected in serum samples with a commercial ELISA kit (Euroimmun).Results:The overall prevalence of anti-CEP1 in CTDs was 7% (15/212 patients). In detail, these antibodies were detectable in 4 out of 85 pSS (5%), 5 out of 51 SLE (10%) and 6/76 SSc (8%). The prevalence and the titer of anti-CEP1 in CTDs was significantly higher compared to NC and significantly lower compared to RA. Anti-CEP1 positive patients did not display a specific clinical and serological picture. Unlike in RA, anti-CEP1 did not correlate with CTD-associated ILD.Conclusion:This is the first study assessing anti-CEP1 in a large cohort of patients with CTDs. We demonstrated that the association of these autoantibodies with ILD is specific for RA since it is not observed in SLE, pSS and SSc. Furthermore, although being significantly more prevalent and at higher titer compared to NC, anti-CEP1 do not allow to discriminate different patient subsets displaying peculiar clinical or serological phenotypes. Based on our results, the application of anti-CEP1 in CTDs is not advisable, however larger studies may possibly identify correlations not evident in our cohort.References:[1] Bonifacio AF, Alunno A, La Paglia GMC, Valentini E, Leone MC, Bartoloni E, Gerli R. Novel autoantibodies in rheumatoid arthritis. Reumatismo 2019;71(1):1-12[2] Alunno A, Bistoni O, Pratesi F, La Paglia GMC, Puxeddu I, Migliorini P, Gerli R. Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone erosion in rheumatoid arthritis. Rheumatology (Oxford). 2018;57(5):850-855Disclosure of Interests:Alessia Alunno: None declared, Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Onelia Bistoni: None declared, Matteo Antonucci: None declared, Elena Bartoloni Bocci: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer, Roberto Gerli: None declared


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
A. Picchianti Diamanti ◽  
V. Germano ◽  
E. Bizzi ◽  
B. Laganà ◽  
A. Migliore

Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFαinhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.


2022 ◽  
Vol 11 (2) ◽  
pp. 410
Author(s):  
Marco Sebastiani ◽  
Caterina Vacchi ◽  
Giulia Cassone ◽  
Andreina Manfredi

Interstitial lung disease (ILD) is one of the most frequent pulmonary complications of autoimmune rheumatic diseases (ARDs), and it is mainly associated with connective tissue diseases (CTDs) and rheumatoid arthritis (RA) [...]


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Albina Tyker ◽  
Iazsmin Bauer Ventura ◽  
Cathryn T. Lee ◽  
Rachel Strykowski ◽  
Nicole Garcia ◽  
...  

AbstractRheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36 months among patients who had high-titer RF seropositivity (≥ 60 IU/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1–6.8; P = 0.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.


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