Op0265 Rituximab Retention Rate in Systemic Sclerosis: A Real-Life Italian Multicenter Study

Background: Rituximab(RTX) has been widely used for the management of systemic sclerosis(SSc), thanks to accumulating evidence about its efficacy for skin and lung fibrosis in some disease subsets. Long-term data on RTX safety and efficacy are limited. Objectives: to assess the real-life RTX retention rate as an indicator of safety and efficacy in a multicentric cohort of Italian SSc patients. Methods: SSc patients treated with RTX and with a follow-up for at least 36 months were retrospectively included and clinically characterized. For all patients a comprehensive evaluation of disease characteristics and organ involvement was available, including. Data on clinical indication for RTX therapy, therapeutic scheme, repeated rituximab courses, previous and concomitant therapies, RTX discontinuations and related reasons and adverse events(AEs) were collected. Patients were longitudinally monitored for up to 5 years. The follow-up period ended at the treatment discontinuation, the death from any cause, or the conclusion of the available follow-up, whichever came first. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of RTX discontinuation. Results: 152 SSc patients (mean age 47.3±12.3 years; females 79.6%; diffuse cutaneous SSc [dcSSc] 77.6%) were evaluated for a median(IQR) time of 3.3(1.7-5.0) years(Table1). The main reasons for RTX prescription were lung fibrosis (38.8%), worsening of skin fibrosis (36.8%), and arthritis (13.8%); 138 patients (90.8%) were treated with ≥1 RTX course (median 4[3-8] courses). Five-year RTX retention rate was 59.9%(44.6-64.7%). A clinical response was the most common cause of RTX discontinuation [5.7 (3.7-8.4) per 100 patient-year] and was associated with a shorter disease duration [sHR 0.8(0.7-0.9)], anti-Scl70 negativity [sHR 0.4(0.2-0.9)], previous digital ulcers[sHR 2.6(1.1-6.2] and no history of arthritis [sHR 0.3(0.1-0.8)]. At 6 months and at final follow-up, skin score significantly improved either in the entire cohort (mRSS: 11.9±8.0 and 8.3±7.4 vs 16.5±9.6) and in dcSSc patients with progressive skin involvement (mRSS: 15.6±9.6 and 9.2±7.9 vs 21.0±10.8)(p<0.001 for all). At 6 months and at final follow-up, mean predicted(%) forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) remained stable both in the entire cohort (FVC: 87.3±21.5 and 87.0±23.5 vs 87.4±19.8; DLCO: 65.2±20.9 and 61.1±19.6 vs 62.1±19.7) and in patients with interstitial lung disease (FVC: 84.7±19.2 and 82.5±21.6 vs 81.6±17.8; DLCO: 64.5±19.0 and 57.9±18.5 vs 60.6±18.7)(p=ns). Treatment failure was the second cause of RTX discontinuation [3.7(2.2-6.0) per 100 patient-year], and was associated with anti-centromere antibody positivity[sHR 2.8 (1.1-7.4)] and anti-Scl70 negativity [sHR 0.2(0.1-0.6)]. Occurrence of adverse events (7 infusion reactions, 4 severe infections, 2 cardiovascular events and one cytopenia) was the less common cause of RTX discontinuation [3.1(1.7-5.2) per 100 patient-year], associated with limited cutaneous subset [sHR 3.4(1.2-9.7)] and previous mycophenolate mofetil treatment [sHR 4.5(1.2-16.3)]. Conclusion: RTX showed a good retention rate and its safety is satisfactory in a real life setting for the treatment of SSc. Indeed, in the long-term follow-up, only few adverse events were shown to limit treatment retention. REFERENCES: NIL. Acknowledgements: We acknowledge GILS (Gruppo Italiano Lotta alla Sclerodermia) for supporting the study Disclosure of Interests: None declared.