SAT0460 HCV-RELATED MIXED CRYOGLOBULINAEMIA IN THE DIRECT-ANTIVIRAL AGENTS ERA: IS THERE ADVANTAGE IN SEQUENTIAL THERAPY WITH RITUXIMAB?

Background: Mixed Cryoglobuminaemia(MC) is a small vessel vasculitis characterized by the presence of a monoclonal rheumatoid factor(RF) and polyclonal immunoglobulins that precipitate at cold temperature, with a large spectrum of clinical manifestations. MC is strongly associated with hepatitis C(HCV) infection>90%. The new direct–acting antivirals(DAA) against HCV, which can eradicate the virus in >95% of patients, are supposed to have benefits on clinical manifestations of MC, nonetheless the amount of data is still limited. Patients with severe vasculitis may require anti-CD20 agent Rituximab(RTX) over DAA. However, despite the strong rationale, the advantage of dual therapy is still debated and the optimal therapeutic schedule unknown. Objectives: To investigate the impact of DAA treatment on clinical manifestations and biochemical parameters of disease activity in HCV-related MC patients who reached complete viral eradication, and if pre-treatment with RTX was able to define a subset of patients with a different outcome. Methods: Data was collected from 31 patients with MC, mean age 68 yrs, female 80%, mean disease duration 10 yrs who were treated with DAA and reached complete viral eradication, at 3 time points: before starting DAA (pre-DDA), after completing DAA (post-DAA), 52 weeks after completing DAA (52w). Additionally, a population of 9 patients with the same disease (mean age 65 yrs, female 77%, mean disease duration 9 yrs) but treated with one or more cycles of RTX prior receiving DAA, was analysed at the same timepoints and additionally before starting RTX(pre-RTX). At each time point clinical data (presence/absence of purpura, neuropathic manifestations, arthralgia, fatigue, nephritis) and biochemical parameters (% cryoglobulins, C3, C4 and RF) were recorded. The change in clinical and biochemical parameters at different timepoints were evaluated. Results: Among patients treated with DAA only, the prevalence of clinical manifestations before starting treatment was the following: purpura 31%,neuropathic manifestations 52%,arthralgia 28%,fatigue 14%, nephritis 3%. We observed a significant reduction in purpura after treatment (pre-DDA vs post-DAA=31% vs 13%,p=0.044) that persisted at 52w (pre-DAA vs 52w=31% vs 0%,p=0.004%). This in parallel with a significant reduction in the level of cryoglobulins (pre-DAA vs 52w=3.99±5.28 vs 1.6 ±1.7,p=0.029 and pre-DAA vs 52w=3.99 ± 5.28 vs 0.92 ± 1.75,p=0.008). Among patients pre-treated with RTX, the prevalence of clinical manifestations before starting RTX was: purpura 78%, neuropathic manifestations 100%,arthralgia 44%,fatigue 50%,nephritis 22%;and before starting DAA was: purpura 22%,neuropathic manifestations 100%,arthralgia 0%,fatigue 0%,nephritis 0%. A significant reduction in the rate of purpura (pre-RTX vs pre-DAA=78% vs 22%, p=0.009%) and arthralgia (44% vs 0%,p=0.012%) after RTX treatment was observed, but no difference in any clinical parameter when comparing pre-RTX with post-DAA and 52w. No significant change in any of the serological parameter was observed. Conclusion: DAA treatment is associated with rapid and sustained decrease in the level of cryoglobulins and related clinical improvement, specifically purpura. Patients who had been pre-treated with RTX showed clinical improvement in terms of purpura and arthralgia, albeit transient; subsequent treatment with DAA did not result in any immediate or long term additional clinical benefit. References [1] Mazzaro C. Clin Exp Rheum2017. Disclosure of Interests: Maria Di Cicco: None declared, Davide Antonio Filippini: None declared, Federica Filippini: None declared, Laura Belloli: None declared, Valeria Campanella: None declared, Cinzia Casu: None declared, Michel Chevallard: None declared, Marina Muscara: None declared, Mariaeva Romano Speakers bureau: janssen, Emanuela Schito: None declared, Elisa Verduci: None declared, Massimo Puoti: None declared, Maria Vinci: None declared, Oscar Massimiliano Epis Speakers bureau: BMS