FRI0228 Safety and efficacy of rituximab in patients with rheumatoid arthritis and lung involvement

Abstract

Background Lung involvement is common in patients with Rheumatoid Arthritis (RA), including interstitial lung disease (ILD), pleural disease and small airway disease. There are no full reports in the literature analyzing the influence of Rituximab (RTX) in patients with RA with pre-existing lung disease, although it is a rising question in daily clinical practice. Objectives We aim to evaluate the safety and efficacy of RTX in our cohort of RA patients with pre-existing lung involvement. Methods Retrospective observational study of the RA cohort treated with RTX at University College Hospital, identifying patients treated with RTX with any lung involvement. Data were collected on type of lung disease, mortality, respiratory infections and stabilization/progression of symptoms. Results 264 patients with RA have received RTX in our unit between 1998 and 2012. A total of 38 patients (14%) had lung involvement, 24 of them (63%) were female, mean age was 64 years (range 37-79), mean disease duration was 19 years (range 3-42), mean number of RTX cycles was 4 (range 1-10), total follow up duration was 146.7 patient years (median 2.5 years, range 0.5-13.5). 19 of them (50%) had ILD: 3 usual interstitial pneumonitis (UIP), 5 nonspecific interstitial pneumonitis (NSIP, 2 of those had an overlap antisyntetase syndrome), 4 organizing pneumonia (OP) and 7 undetermined ILD. 15 patients (40%) had bronchiectasis. The remaining 4 patients had diagnosis of chronic obstructive pulmonary disease (COPD), small airway disease, pleural effusion requiring decortication and pleural plaques. 6 of the above patients had concomitant COPD. Lung disease has remained clinically and radiologically stable in most patients. One patient with severe UIP before RTX showed slow lung progression over 4 years of follow up, and Mycophenolate mofetil is being considered. The 2 patients with antisynthetase syndrome have stable NSIP but on combination therapy (1 azathioprine, 1 mycophenolate mofetil). 25 patients (66%) reported respiratory infections but in only 6 of these patients was an increased frequency of infections after starting rituximab treatment noted. 2 of these 6 patients had low serum immunoglobulins (1 IgG only, 1 IgG and IgM). 2 patients had serious infections requiring hospitalization. There were 2 deaths, both in patients with bronchiectasis and multiple comorbidities, none directly related to rituximab treatment. Conclusions RTX seems to be a relatively safe therapy in the cohort of RA patients with lung involvement. There is no definite evidence for improvement in lung involvement in RA patients treated with rituximab, but nor there is data suggesting that RTX can lead to a progression of lung symptoms. Only one patient with severe UIP before RTX showed lung progression after 4 years of follow up. Disclosure of Interest: E. Becerra: None Declared, G. Cambridge: None Declared, M. Leandro Grant/research support from: GSK, Abbott., Consultant for: Roche, Chugai

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

“…Finally, Becerra et al didn't experience respiratory improvement in 19 patients with established RA-ILD over four years, and 15 patients (66%) reported respiratory infections. [166].…”

“…Yusof, 2017 [154] retrospective observational study 44 Fui A, 2019 [164] retrospective study 14 Duarte AC, 2019 [15] retrospective study 17 Other articles * Becerra E, 2012 [166] abstract 19 Keir GJ, 2014 [162] retrospective study 2…”

“…In patients with active joint disease and subclinical non-progressive ILD, current therapy with DMARDs (including MTX and TNFi) should be continued to achieve low disease activity; while in patients starting a new DMARD, the use of ABA, JAK inhibitors, IL6 inhibitors or RTX could be appropriate [39,40,109]. However, we caution about the use of RTX in patients at a high risk of infections of the lower respiratory tract [49,50,166]. The association with MTX should be evaluated in every single patient.…”

Rituximab therapy in interstitial lung disease associated with rheumatoid arthritis

“…However, a high incidence of pulmonary toxicity is reported in patients treated for lymphoma and/or in some patients with RA . Controversial results have been reported on rituximab efficacy in RA‐ILD patients and our study will contribute to this topic by describing the characteristics of 28 patients treated with RA‐ILD focusing mainly in those with anti‐CD20.…”

Treatment Considerations of Lung Involvement in Rheumatologic Disease

“…A recent clinical trial focusing on patients with NSIP or UIP patterns has shown stabilization or improvement in PFT, imaging studies, joint symptoms and quality of life in 6 out of 7 patients [41]. The safety and tolerability of rituximab has been tested, and only induced inflammatory disorders that improved with corticosteroids have been reported [42,43,44,45]. Based on these results, some groups initiate rituximab when corticosteroids and other immunosuppressors fail to inhibit the progression of RA-ILD.…”