Real-world clinical effectiveness of rituximab rescue therapy in patients with progressive rheumatoid arthritis-related interstitial lung disease

Narváez, Javier; Robles-Pérez, Alejandro; Molina-Molina, María; Vicens-Zygmunt, Vanesa; Luburich, Patricio; Yañez, Marcos Anibal; Alegre, J.J.; Nolla, Joan M.

doi:10.1016/j.semarthrit.2020.08.008

Cited by 34 publications

(34 citation statements)

References 47 publications

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“…Despite this, the optimal treatment strategy for such patients remains unknown, reflecting a paucity of randomized controlled clinical trials for this patient sub-group. Recently, observational data have suggested treatment with rituximab [6,15,16], and laterally abatacept [5,17] is the most effective and safest biologic agents for the treatment of RA with concurrent ILD or bronchiectasis. Data suggest that treatment with rituximab and abatacept may even infer a benefit to pulmonary function [5,6].…”

Section: Discussionmentioning

confidence: 99%

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease

et al. 2021

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Janus kinase inhibitors (JAKi) are an exciting option for the treatment of rheumatoid arthritis (RA) but little is known about their safety and tolerability in patients with existing respiratory disorders. The objective was to compare pulmonary safety of JAKi versus rituximab in patients with concurrent interstitial lung disease (ILD) or bronchiectasis. We performed a retrospective electronic patient record review of patients with known ILD or bronchiectasis commencing JAKi or rituximab for the treatment of RA. Patients initiating treatment from January 2016 to February 2020 were included. Respiratory events (hospitalization or death from a respiratory cause) were compared using Kaplan–Meier survival analysis. We analysed patients who received JAKi (n = 28) and rituximab (n = 19) for a mean (SD) of 1.1 (0.62) and 2.14 (1) years respectively. Patients were predominantly female (68%), anti-CCP antibody positive (94%) and non-smoking (89%) with a median (IQR) percentage predicted FVC at baseline of 100% (82–115%) and percentage predicted TLCO of 62% (54.5–68%). Respiratory events occurred in five patients treated with JAKi (18%; 5 hospitalizations, 2 deaths) and in four patients treated with rituximab (21%; 3 hospitalizations, 1 death). Respiratory event rates did not differ between groups (Cox-regression proportional hazard ratio = 1.38, 95% CI 0.36–5.28; p = 0.64). In this retrospective study, JAKi for the treatment of RA with existing ILD or bronchiectasis did not increase the rate of hospitalization or death due to respiratory causes compared to those treated with rituximab. JAK inhibition may provide a relatively safe option for RA in such patients.

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Section: Discussionmentioning

confidence: 99%

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease

et al. 2021

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“…However, we were able to fulfill the main objective of the study, which was to report on the efficacy and safety profile of rituximab in different CTD-ILDs, showing the results in each of them separately. Lastly, despite there being no differences between the subgroups of patients treated with rituximab in terms of the primary endpoint of pulmonary outcome (p = 0.179), there was a greater number of patients with SS who presented progression compared to RA and IM [15,52]. However, the low number of cases included may not be sufficient to reveal significant differences between the groups, despite most studies to date being based on small retrospective observational studies.…”

Section: Discussionmentioning

confidence: 93%

“…However, other authors reached contrasting conclusions, especially with respect to the efficacy of rituximab in ILD associated with other CTDs, and particularly with RA-ILD, given that survival in affected patients has been shown to be lower than in other CTD-ILDs [34,35]. A recent study [15] showed that rituximab can be effective as a rescue therapy in a considerable percentage of patients with progressive RA-ILD that does not respond to standard treatment. In our study, these differences were not statistically significant, despite the higher number of patients whose disease progressed or who died among those with RA treated with rituximab.…”

Section: Discussionmentioning

confidence: 99%

“…However, one meta-analysis did not report a higher frequency of respiratory adverse effects [14]. As for biologic DMARDS (bDMARDs), the available evidence-based mainly on cross-sectional and retrospective studies-suggests that rituximab and abatacept could be safe for CTD-ILD treatment [6,[15][16][17][18][19][20][21][22]. Tocilizumab has also been suggested to be effective in preserving lung function in SS [23].…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Rituximab in Autoimmune Disease—Associated Interstitial Lung Disease: A Prospective Cohort Study

Mena-Vázquez

Redondo-Rodríguez

Rojas-Giménez

et al. 2022

JCM

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Objectives: To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD). Methods: We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving rituximab between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline, at 12 months, and at the end of follow-up. The main outcome measure at the end of follow-up was forced vital capacity (FVC) > 10% or diffusing capacity of the lungs for carbon monoxide (DLCO) > 15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening ILD. Results: We included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7–69.0) months. At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in seven (18.9%); seven patients (18.9%) died. No significant decline was observed in median FVC (72.2 vs. 70.8; p = 0.530) or DLCO (55.9 vs. 52.2; p = 0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR (95% CI), 0.904 (0.8–0.9); p = 0.015), time to initiation of RTX (1.01 (1.001–1.02); p = 0.029), and mycophenolate (0.202 (0.04–0.8); p = 0.034). Only 28 of the 37 patients (75.6%) were still undergoing treatment with RTX: two patients (5.4%) stopped treatment due to adverse events and seven patients (18.9%) died owing to progression of ILD and superinfection. Conclusion: Lung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD.

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“…Similarly, antifibrotic agents, such as nintedanib, could have a beneficial effect on the lungs of affected patients, as shown by the studies SENSCIS [27] and INBUILD [28]. In recent years, treatment with the immunosuppressants rituximab and abatacept has been reported to be safe and effective in ILD-SAI [29][30][31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arthritis Compared with Other Autoimmune Disease: A Retrospective Cohort Study

et al. 2021

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Objectives: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. Patients and methods: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. Results: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8–93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3–2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0–2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4–3.9]), and smoking (HR, 2.7 [95%CI, 1.6–4.7]). Conclusion: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.

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Real-world clinical effectiveness of rituximab rescue therapy in patients with progressive rheumatoid arthritis-related interstitial lung disease

Cited by 34 publications

References 47 publications

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease

Efficacy and Safety of Rituximab in Autoimmune Disease—Associated Interstitial Lung Disease: A Prospective Cohort Study

Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arthritis Compared with Other Autoimmune Disease: A Retrospective Cohort Study

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