SAT0460 HCV-RELATED MIXED CRYOGLOBULINAEMIA IN THE DIRECT-ANTIVIRAL AGENTS ERA: IS THERE ADVANTAGE IN SEQUENTIAL THERAPY WITH RITUXIMAB?
Authors: Maria Di Cicco, Davide Antonio Filippini, Federica Filippini, Laura Belloli, Valeria Campanella, Cinzia Casu, Michel Chevallard, Marina Muscarà, Mariaeva Romano, Emanuela Schito, Elisa Verduci, Massimo Puoti, Maria Vinci, Oscar Massimiliano Epis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> 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&gt;90%. The new direct–acting antivirals(DAA) against HCV, which can eradicate the virus in &gt;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. <h3>Objectives:</h3> 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. <h3>Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusion:</h3> 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. <h3>References</h3> [1] Mazzaro C. Clin Exp Rheum2017. <h3>Disclosure of Interests:</h3> 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 Muscarà: 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