Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study

Abstract

ObjectiveTo assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis

“…Consistent with previous reports, Th2 cell numbers were greatly increased in bullous pemphigoid tissues and outnumbered those in SSc and healthy control skin ( Figure 2C and Supplemental Figure 2). Despite the 5-to 10-fold greater number of CD4 + T cells in skin biopsies of bullous pemphigoid patients compared with SSc biopsies, we found the absolute numbers of tissue-infiltrating T lymphocytes have not been systematically interrogated at the tissue level (22)(23)(24).…”

“…Although prominent numbers of both B and T cells were observed, the absolute number of infiltrating T cells was greater than those of infiltrating B cells ( Figure 1, A and B). Although randomized double-blind clinical trials examining the utility of B cell depletion therapy in SSc have not been performed, some studies have reported clinical improvement with rituximab, especially in the context of early diffuse SSc (22,23). Additionally, activated B cells have been observed in the circulation of SSc patients (24,36).…”

Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti‐topoisomerase I‐positive systemic sclerosis‐associated interstitial lung disease

“…In conclusion, from our study, RTX has been shown to be a more effective drug than CYC for Japanese SSc patients. Whereas, there are some studies in which the change of pulmonary function and skin sclerosis by RTX treatment was not statistically significant . There are some factors that explain the good response to the treatment in our study.…”

“…Whereas, there are some studies in which the change of pulmonary function and skin sclerosis by RTX treatment was not statistically significant. 46,47 There are some factors that explain the good response to the treatment in our study. For example, difference in the duration of disease, the presence of anti-topo I antibodies, the levels of serum KL-6, and the severity of lung fibrosis might be related to this result.…”

Current and future perspectives on management of systemic sclerosis-associated interstitial lung disease

“…A follow-up study of 254 patients in the EUSTAR database treated with rituximab, of whom 58% were treated for lung involvement, did not show effects on FVC or DLco. After a median follow-up of 2 years, compared to 9575 control patients matched for propensity score, rituximab-treated patients were more likely to have an improvement in skin fibrosis, but did not have significantly different rates of decline in FVC or DLco [69]. An ongoing multicenter randomized trial in the UK, RECITAL, is assessing the efficacy and safety of rituximab given intravenously at baseline and week 2 versus monthly intravenous CYC in 116 subjects with ILD associated with SSc, idiopathic inflammatory myositis, or mixed connective tissue disease [70].…”