Rituximab retention rate in systemic sclerosis: a long term real-life multicentre study

Objectives To report real-life data on rituximab retention rate as an indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients.Methods SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized and longitudinally monitored. A competing risk analysis with sub-hazard ratio (sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation.Results One-hundred and fifty-two SSc-patients [mean age 47.3 (12.3) years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%] were evaluated over a median (interquartile range) time of 3.3 (1.7-5.0) years. The primary indications for rituximab were interstitial lung disease (38.8%), worsening skin fibrosis (36.8%) and arthritis (13.8%); 138 patients (90.8%) received more than one rituximab course. The 5-year rituximab retention rate was 59.9% (44.6-64.7%). Clinical response was the most common reason for rituximab discontinuation [5.7; 95% CI: (3.7-8.4) per 100 patient-years] and was associated with a shorter disease duration (sHR 0.8; 95% CI: 0.7, 0.9), anti-topoisomerase-I negativity (sHR 0.4; 95% CI: 0.2, 0.9), previous digital ulcers (sHR 2.6; 95% CI: 1.1, 6.2) and no history of arthritis (sHR 0.3; 95% CI: 0.1, 0.8). Treatment failure was the second cause of rituximab discontinuation [3.7 (95% CI: 2.2, 6.0) per 100 patient-years] and was associated with anti-centromere antibody positivity (sHR 2.8; 95% CI: 1.1, 7.4) and anti-topoisomerase-I negativity (sHR 0.2; 95% CI: 0.1, 0.6). Adverse events (AEs) were the less common cause of discontinuation [3.1 (95% CI: 1.7, 5.2) per 100 patient-years], associated with limited cutaneous subset (sHR 3.4; 95% CI: 1.2, 9.7) and previous mycophenolate mofetil treatment (sHR 4.5; 95% CI: 1.2, 16.3).Conclusion Rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients.