Main Article Content
Rheumatoid arthritis, interstitial lung disease, progression, rituximab
Objective. To demonstrate the effects of rituximab (RTX) in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD). Methods. A total of 165 patients who used RTX for the management of rheumatoid arthritis were retrospectively scrutinised. Among these, 26 patients diagnosed with RA-ILD were analysed (61.5% male, mean age at RTX infusion 61.4 ± 6.5 years). To evaluate the efficacy of RTX on lung response, patients with pulmonary function test results and/or thorax computed tomography (chest-CT) of pre- and post-RTX were compared. Disease progression was defined as either a decline of ≥10% in forced vital capacity (FVC) and/or a decline of ≥15% in diffusion capacity of carbon monoxide (DLCO), or an increase of parenchymal involvement on chest-CT images according to the radiologists’ assessment. Results. Among 26 patients, the most common radiologic pattern was usual interstitial pneumonia (42.3%), followed by non-specific interstitial pneumonia (38.5%). Data for lung response was available in 20 patients. Median pre- and post- RTX DLCO values were 71.0% (60.0-77.0) and 63.0% (47.0-74.0), respectively (p= 0.06). Median pre- and post-RTX FVC values were 74.0% (61.0-99.0) and 84.0% (63.0-100.0), respectively (p= 0.28). Overall, stabilization or regression of RA-ILD was provided in 13 (65.0%) patients, whereas 7 patients had progressive RA-ILD. Post-RTX, 5 patients were diagnosed with RA-ILD. Conclusion. Our results suggest that RTX is effective in achieving stabilization or even improvement of RA-ILD. However, considering that it does not cause regression in every patient and some develop RA-ILD under RTX, we still need more effective treatment options.
2. Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis. 2003;62(8):722-7.
3. Duarte AC, Porter JC, Leandro MJ. The lung in a cohort of rheumatoid arthritis patients-an overview of different types of involvement and treatment. Rheumatology (Oxford). 2019;58(11):2031-8.
4. Huang S, Doyle TJ, Hammer MM, Byrne SC, Huang W, Marshall AA, et al. Rheumatoid arthritis-related lung disease detected on clinical chest computed tomography imaging: Prevalence, risk factors, and impact on mortality. Semin Arthritis Rheum. 2020;50(6):1216-25.
5. Hyldgaard C, Hilberg O, Pedersen AB, Ulrichsen SP, Løkke A, Bendstrup E, et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis. 2017;76(10):1700-6.
6. Kelly CA, Saravanan V, Nisar M, Arthanari S, Woodhead FA, Price-Forbes AN, et al. Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study. Rheumatology (Oxford). 2014;53(9):1676-82.
7. Koduri G, Norton S, Young A, Cox N, Davies P, Devlin J, et al. Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort. Rheumatology (Oxford). 2010;49(8):1483-9.
8. Bongartz T, Nannini C, Medina-Velasquez YF, Achenbach SJ, Crowson CS, Ryu JH, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2010;62(6):1583-91.
9. Li L, Liu R, Zhang Y, Zhou J, Li Y, Xu Y, et al. A retrospective study on the predictive implications of clinical characteristics and therapeutic management in patients with rheumatoid arthritis-associated interstitial lung disease. Clinical rheumatology. 2020;39(5):1457-70.
10. Md Yusof MY, Kabia A, Darby M, Lettieri G, Beirne P, Vital EM, et al. Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years' experience at a single centre. Rheumatology (Oxford). 2017;56(8):1348-57.
11. Kelly CA, Nisar M, Arthanari S, Carty S, Woodhead FA, Price-Forbes A, et al. Rheumatoid arthritis related interstitial lung disease - improving outcomes over 25 years: a large multicentre UK study. Rheumatology (Oxford). 2020.
12. Vadillo C, Nieto MA, Romero-Bueno F, Leon L, Sanchez-Pernaute O, Rodriguez-Nieto MJ, et al. Efficacy of rituximab in slowing down progression of rheumatoid arthritis-related interstitial lung disease: data from the NEREA Registry. Rheumatology (Oxford). 2020;59(8):2099-108.
13. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-81.
14. Sverzellati N, Lynch DA, Hansell DM, Johkoh T, King TE, Jr., Travis WD. American Thoracic Society-European Respiratory Society Classification of the Idiopathic Interstitial Pneumonias: Advances in Knowledge since 2002. Radiographics. 2015;35(7):1849-71.
15. Demoruelle MK, Weisman MH, Simonian PL, Lynch DA, Sachs PB, Pedraza IF, et al. Brief report: airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity? Arthritis Rheum. 2012;64(6):1756-61.
16. Scher JU, Joshua V, Artacho A, Abdollahi-Roodsaz S, Öckinger J, Kullberg S, et al. The lung microbiota in early rheumatoid arthritis and autoimmunity. Microbiome. 2016;4(1):60.
17. Sparks JA, He X, Huang J, Fletcher EA, Zaccardelli A, Friedlander HM, et al. Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Prospective Cohort Study. Arthritis Rheumatol. 2019;71(9):1472-82.
18. Li L, Liu R, Zhang Y, Zhou J, Li Y, Xu Y, et al. A retrospective study on the predictive implications of clinical characteristics and therapeutic management in patients with rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol. 2020;39(5):1457-70.
19. Ledingham J, Gullick N, Irving K, Gorodkin R, Aris M, Burke J, et al. BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs. Rheumatology (Oxford). 2017;56(6):865-8.
20. Dawson JK, Fewins HE, Desmond J, Lynch MP, Graham DR. Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis. Ann Rheum Dis. 2002;61(6):517-21.
21. Atkins SR, Turesson C, Myers JL, Tazelaar HD, Ryu JH, Matteson EL, et al. Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis-associated nonspecific interstitial pneumonia and usual interstitial pneumonia. Arthritis Rheum. 2006;54(2):635-41.
22. Duarte AC, Cordeiro A, Fernandes BM, Bernardes M, Martins P, Cordeiro I, et al. Rituximab in connective tissue disease-associated interstitial lung disease. Clin Rheumatol. 2019;38(7):2001-9.
23. Robles-Perez A, Dorca J, Castellví I, Nolla JM, Molina-Molina M, Narváez J. Rituximab effect in severe progressive connective tissue disease-related lung disease: preliminary data. Rheumatol Int. 2020;40(5):719-26.
24. Druce KL, Iqbal K, Watson KD, Symmons DPM, Hyrich KL, Kelly C. Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic. RMD Open. 2017;3(1):e000473.
25. Md Yusof MY, Iqbal K, Darby M, Lettieri G, Vital EM, Beirne P, et al. Effect of rituximab or tumour necrosis factor inhibitors on lung infection and survival in rheumatoid arthritis-associated bronchiectasis. Rheumatology. 2020;59(10):2838-46.