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Efficacy and Safety of Sofosbuvir plus Daclatasvir for Treatment of HCV-associated Cryoglobulinemia Vasculitis.
Saadoun D, et al.
Gastroenterology 2017

Abstract: Circulating mixed cryoglobulins are detected in 40%–60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in about 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct acting antiviral drugs in these patients.
We performed open-label, prospective, multi-center study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 years; 53.6% women) were recruited from hospitals in Paris, France from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n=32) or 24 weeks (n=9) and evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis.
Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks' therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56±0.18 at baseline to 0.21±0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T regulatory cells, IgM+CD21–/low memory B cells, CD4+CXCR5+ IL21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20–30 months), no patients had a serious adverse event or relapse of vasculitis.

Expert's Commentary (Dr Jordan Feld, senior author)

Treatment of mixed cryoglobulinemic vasculitis (MCV) was a significant challenge with interferon-based therapy. Although some patients improved, tolerability was very poor and only a minority achieved SVR. Everything has changed with DAAs. In this study, Saadoun and colleagues report on 41 patients with symptomatic MCV who received sofosbuvir and daclatasvir. All achieved SVR but more importantly all but 4 (90%) had complete resolution of vasculitic manifestations. Not surprisingly, treatment was well tolerated and by 2 years of follow-up, no patients had relapsed despite the fact that only 50% had cleared cryoglobulins from the serum. This study has reported better and more rapid improvement in clinical outcomes than other evaluations of patients with MCV treated with DAAs, possibly owing to the inclusion of patients with relatively mild MCV. The very positive results make a further case for treating patients with cryoglobulinemia early to prevent serious disease manifestations that may be less likely to resolve with viral clearance.

Jordan Feld MD MPH, University of Toronto, Ontario, Canada