Rituximab combined with Peg-interferon-ribavirin in refractory hepatitis C virus-associated cryoglobulinaemia vasculitis

• Published in: Annals of the rheumatic diseases Vol. 67; no. 10; pp. 1431 - 1436
• Main Authors: Saadoun, D, Resche-Rigon, M, Sene, D, Perard, L, Karras, A, Cacoub, P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.10.2008; BMJ; BMJ Publishing Group LTD
• Subjects: Adult; Aged; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived; Antiviral Agents - therapeutic use; Biological and medical sciences; Cryoglobulinemia - complications; Cryoglobulinemia - drug therapy; Diseases of the osteoarticular system; Drug Therapy, Combination; Female; Hepatitis; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; HIV; Human immunodeficiency virus; Humans; Immunology; Immunomodulators; Infections; Interferon-alpha - therapeutic use; Lymphoma; Male; Medical sciences; Middle Aged; Patients; Pharmacology. Drug treatments; Pilot Projects; Polyethylene Glycols; Recombinant Proteins; Ribavirin - therapeutic use; Rituximab; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Treatment Outcome; Vasculitis - drug therapy; Vasculitis - virology; Antineoplastic agent; Immunopathology; Cryoglobulinemia; Rheumatology; Rituximab; Cardiovascular disease; Ribavirin; Vascular disease; Virus; Ethylene oxide polymer; Immunomodulator; Refractory; Vasculitis; Immunoglobulinopathy; Antiviral; Interferon; Immunosuppressive agent; Flaviviridae; Hepatitis C virus; Hepacivirus
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2007.081653

Objectives:To report the results of a pilot study using rituximab combined with Peg-interferon (IFN) α2b-ribavirin in severe refractory hepatitis C virus (HCV) related mixed cryoglobulinaemia (MC) vasculitis.Methods:Sixteen consecutive patients with severe HCV-MC vasculitis that were resistant (n = 11) or relapser (n = 5) to a previous combination treatment with standard (n = 10) or Peg-IFNα2b (n = 6) plus ribavirin were included. They were treated with rituximab (375 mg/m2 intravenously weekly for 4 weeks) combined with Peg-IFNα2b (1.5 μg/kg per week subcutaneously) plus ribavirin (600–1200 mg/day orally) for 12 months.Results:Fifteen patients (93.7%) showed clinical improvement, 10 of whom (62.5%) were clinical complete responders (CR). HCV RNA and serum cryoglobulin became undetectable in all the clinical CR. Peripheral blood B cell depletion was achieved in all patients (CD19+ cells, 111 (SD 32)/mm3 at baseline versus 2(2)/mm3 after the fourth infusion of rituximab) with reconstitution starting at the end of antiviral treatment. Compared with clinical CR, the partial or non-responders had a 3.6 times longer duration of vasculitis prior to treatment and a lower rate of early virological response. Treatment was well tolerated with no infectious complications. After a mean follow-up of 19.4 (SD 3.6) months, two patients experienced clinical relapse associated with a simultaneous reappearance of HCV RNA and cryoglobulin and an increase in the number of B cells.Conclusions:Rituximab combined with Peg-IFNα2b-ribavirin represents a safe and effective treatment option in severe refractory HCV-MC vasculitis.