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

De Luca, Giacomo; De Lorenzis, Enrico; Campochiaro, Corrado; Cacciapaglia, Fabio; Del Papa, Nicoletta; Zanatta, Elisabetta; Airò, Paolo; Lazzaroni, Maria Grazia; Giuggioli, Dilia; De Santis, Maria; Alonzi, Gabriella; Stano, Stefano; Binda, Marco; Moccaldi, Beatrice; Tonutti, Antonio; Cavalli, Silvia; Batani, Veronica; Natalello, Gerlando; Iannone, Florenzo; D'Agostino, Maria Antonietta; Dagna, Lorenzo; Matucci-Cerinic, Marco; Bosello, Silvia Laura

doi:10.1093/rheumatology/keae280

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.

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.

Rituximab retention rate in systemic sclerosis: a long term real-life multicentre study / De Luca, G., De Lorenzis, E., Campochiaro, C., Cacciapaglia, F., Del Papa, N., Zanatta, E., Airò, P., Lazzaroni, M.G., Giuggioli, D., De Santis, M., Alonzi, G., Stano, S., Binda, M., Moccaldi, B., Tonutti, A., Cavalli, S., Batani, V., Natalello, G., Iannone, F., D'Agostino, M.A., et al.. - In: RHEUMATOLOGY. - ISSN 1462-0324. - 64:3(2025), pp. 1284-1291. [10.1093/rheumatology/keae280]