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HCV-associated cryoglobulinaemic vasculitis: triple/dual antiviral treatment and/or rituximab?
  1. Tatiana Ignatova,
  2. Olga Chernova,
  3. Pavel Novikov,
  4. Sergey Moiseev
  1. Clinic of Nephrology, Internal and Occupational Diseases, First Moscow State Medical University, Moscow, Russia
  1. Correspondence to Professor Sergey Moiseev, Clinic of Nephrology, Internal and Occupational Diseases, First Moscow State Medical University, Rossolimo, 11/5, Moscow 119992, Russia; clinpharm{at}mtu-net.ru

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Mixed cryoglobulinaemia (MC) vasculitis is a relatively uncommon systemic vasculitis that may be primary or associated with hepatitis C virus (HCV). We have found MC and cryoglobulinaemic vasculitis in 420 (31%) and 65 (5%) of 1351 patients with HCV infection, respectively. Two recent randomised controlled trials have established the superiority of rituximab over conventional immunosuppressive treatment in patients with MC vasculitis1 ,2 while Saadoun et al3 have previously shown that dual antiviral treatment with interferon α and ribavirin had induced remission of HCV-associated MC vasculitis in 63% of 72 consecutive patients and sustained virological response in 58% of cases. In a study recently published in the Annals of the Rheumatic Diseases,4 the same authors suggested that triple antiviral treatment with peginterferon-α–ribavirin–protease inhibitor was highly effective in MC vasculitis associated with genotype 1 HCV infection though grades 3 and 4 adverse events were reported in 44% of cases and the majority of patients required erythropoietin and/or red cell transfusion.

In our series, 65 patients with HCV-associated MC vasculitis were treated with conventional immunosuppressive drugs only (n=30), monotherapy with interferon-α (n=9) or rituximab (n=8) or peginterferon-α–ribavirin±rituximab (n=18). In the last subgroup, rituximab was administered 1 month prior to antiviral treatment in six patients with high activity of vasculitis and visceral manifestations. Our data confirmed higher efficacy of antiviral treatment±rituximab that seemed to numerically prolong relapse-free survival in patients with MC vasculitis compared with conventional immunosuppression or rituximab only (figure 1) though we acknowledge the lack of randomisation and the small number of patients. Monotherapy with interferon-α induced deterioration of vasculitis in 5 (71%) of seven patients while the same effect was observed in only 1 (6%) of 18 patients treated with dual combination±rituximab. In our opinion, higher safety of peginterferon-α–ribavirin compared with short-acting interferon α was related to more rapid and profound suppression of virus replication and confirmed the priority of effective anti-HCV treatment in patients with cryoglobulinaemic vasculitis. Combination antiviral treatment was completed in 16 of 18 patients. Sustained virological response was achieved in 8 (53%) of 15 patients with genotype 1 and all three patients with genotype 2 or 3 infection. Haematological complications developed in 7 (39%) of 18 patients who were treated with peginterferon-α and ribavirin. Four patients presented with grade 1 anaemia, while three patients had grade 3 anaemia (in combination with grade 3 leucopenia and grade 2 thrombocytopenia in one patient) that required erythropoeitin administration or antiviral drug dose reduction. Thus, the incidence of severe haematological disorders in our series (22%) was almost twice lower than in the Saadoun et al4 study.

Figure 1

Relapses-free survival in patients with hepatitis C virus-associated mixed cryoglobulinaemia vasculitis who were treated with conventional immunosuppression, rituximab or peginterferon-α/ribavirin.

In conclusion, our data suggest that peginterferon-α–ribavirin±rituximab increase relapse-free survival compared with standard immunosuppression and rituximab only and induce sustained virological response in more than half of patients with MC vasculitis associated with genotype 1 HCV. We agree with Saadoun et al that peginterferon-α–ribavirin–protease inhibitor combination is more effective than dual antiviral treatment in genotype 1 HCV infection and that higher risk of adverse events should be taken into account in patients with cryoglobulinaemic vasculitis who are probably more prone to haematological complications of triple combination. Dual antiviral treatment is better tolerated and in our opinion can be offered to patients with higher probability of sustained virological response to peginterferon-α–ribavirin, for example, with favourable interleukin-28B polymorphism. Recently, a large scale trial showed high efficacy and excellent safety of the single tablet regimen of ledipasvir–sofosbuvir for primary patients with HCV genotype 1 infection.5 The study of these and other interferon-free regimens are also warranted in patients with HCV-associated MC vasculitis.

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Footnotes

  • Contributors All authors contributed to follow-up of the patients and review of the manuscript.

  • Competing interests None.

  • Ethics approval Retrospective data in patients treated in real-life practice.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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