Rheumatology Advance Access originally published online on May 5, 2006
Rheumatology 2006 45(6):783-784; doi:10.1093/rheumatology/kel134
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LETTER TO THE EDITOR |
Treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia—anti-viral therapy vs rituximab
1 The Feinstein Institute for Medical Research, North Shore-LIJHS, 350 Community Drive, Manhasset, NY 11030, USA, 2 Division of Renal Medicine, Karolinska University Hospital/Huddinge, Karolinska Institutet, S-141 86 Stockholm, Sweden and 3 Department of Internal Medicine and CNRS UMR 7087, Hôpital La Pitié-Salpêtrière, 83, Boulevard de l’Hôpital, 75651 Cedex 13 Paris, France
Correspondence to: A. Bruchfeld. E-mail: Amette.Bruchfeld{at}ki.se
SIR, Quartuccio et al. [1] reported a case series of five patients with HCV-associated mixed cryoglobulinaemic vasculitis. Two of the patients had previously received pegylated interferon, but none had been treated with ribavirin. Another two patients were reported to have milder chronic hepatitis upon liver biopsy and were infected with genotype 2a/2c, both of who are associated with a high likelihood of a sustained viral response (SVR) with anti-viral therapy. Even though the authors reported a rapid renal response, three patients relapsed after 5, 7 and 12 months, respectively, leading to renewed therapy in two patients. Rheumatoid factor, a surrogate marker for cryoglobulinaemia in many cases, remained positive in all patients as well as measurable levels of cryoglobulins in most cases. The authors suggest that rituximab could be used as a first-line therapy in this condition. We strongly question this recommendation based on our own experience with anti-viral therapy.
In a recent study, we showed a high clinical response (88%) and a high SVR (77%) in 9 patients with HCV-MC vasculitis, in spite of most patients being infected with HCV genotype 1, which is more difficult to treat [2]. The treatment used was pegylated interferon-
-2b 1.5 µg/kg/week together with ribavirin 800–1200 mg/day for 13 months, preceded by short-term low-dose corticosteroids in two cases. Supportive therapy for nephrotic-range proteinuria such as furosemide and ACE-inhibitors was given. In another study, seven renal-insufficient patients (GFR 10–65 ml/min at presentation) with HCV-associated GN were given combined ribavirin with interferon- or pegylated interferon [3]. Ribavirin therapy was controlled with an HPLC-method aiming at a target concentration of 10–15 µmol/l. The ribavirin dose was in the range of 200–800 mg/day. Five out of seven patients had an SVR and a clinical response, whereas one patient was re-treated due to viral relapse and was eventually cleared of the virus. One patient was intolerant to interferon but had a sustained clinical remission for several years with ribavirin monotherapy with a GFR between 35–40 ml/min. Tolerance in most cases was good. If necessary, ribavirin-induced anaemia was supported with erythropoietin (4000–20 000 IU/week) and low doses of iron.
Although these two studies were not controlled, the combined SVR and good clinical response in 13 out of 16 patients does not support the use of rituximab as a first-line therapy for HCV-MC with or without GN. We therefore strongly recommend pegylated interferon and ribavirin as a first-line therapy with optimal doses. It appears possible to treat patients with reduced renal function without having to exclude the use of ribavirin by using reduced ribavirin doses and supportive therapy for ribavirin-induced anaemia. The long-term hazard of recurrent use of rituximab in this setting is not clear. In a recent article by Basse et al. [4], rituximab therapy was used for de novo mixed cryoglobulinaemia in renal transplant patients [4]. Severe infectious complications occurred likely to be related to their immunosuppressive state, which could have implications for patients with other immunosuppressive conditions such as cirrhosis and renal insufficiency. We, however, believe that anti-CD-20 compound may be useful in some instances, e.g. non-responders to anti-viral therapy, decompensated cirrhosis, aggressive vasculitic disease, and HCV-associated lymphoproliferative disorder. Anti-viral therapy can still be successful after the use of rituximab as described by Lamprecht et al. [5].
To conclude, we believe that anti-viral therapy will and should remain a first-line therapy for GN in HCV-associated mixed cryoglobulinaemia.
Dr Bruchfeld has conducted research supported by Schering-Plough and Roche.
References
- Quartuccio L, Soardo G, Romano G et al. Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids. Rheumatology 2006. January 17 [Epub ahead of print].
- Cacoub P, Saadoun D, Limal N, Sene D, Lidove O, Piette JC. PEGylated interferon alfa-2b and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum 2005;52:911–5.[CrossRef][Medline]
- Bruchfeld A, Lindahl K, Ståhle L, Söderberg M, Schvarcz R. Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant 2003;18:1573–80.
[Abstract/Free Full Text] - Basse G, Ribes D, Kamar N et al. Rituximab therapy for de novo mixed cryoglobulinemia in renal transplant patients. Transplantation 2005;80:1560–4.[CrossRef][Web of Science][Medline]
- Lamprecht P, Lerin-Lozano C, Merz H et al. Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis. Ann Rheum Dis 2003;62:1230–3.
[Abstract/Free Full Text]
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