RESUMO
OBJECTIVE: To evaluate whether rituximab at a low dose of 250 mg/m(2) × 2 may be as effective as at higher dosages, most commonly 375 mg/m(2)×4, used in previous studies on the treatment of patients with refractory mixed cryoglobulinemia (MC) vasculitis associated with hepatitis C virus (HCV) infection. METHODS: We conducted a phase 2, single-arm two-stage trial (EUDRACT n. 2008-000086-38) of low-dose rituximab in 52 patients with HCV-associated MC who were ineligible/intolerant or non-responder to antiviral therapy. The primary outcomes were response of vasculitis evaluated by the Birmingham Vasculitis Activity Score (BVAS) at months 3, 6 and 12, rate of relapses and time to relapse, and rate of adverse events. Our data were compared with those reported in 19 published studies selected among 291 reviewed in a literature search. RESULTS: The cumulative response rate (complete and partial) at month 3 was 81% in our patients, and 86% in 208 patients from studies using high-dose rituximab. The relapse rate and median time to relapse were, respectively, 41% and 6 months in our study, and 32% and 7 months in high-dose studies. Treatment-related adverse events were 11.5% in our study and 19.9% in high-dose studies. None of these differences was statistically significant. CONCLUSION: Rituximab at a low dosage of 250 mg/m(2) × 2 is as effective as at higher dosages for treating MC vasculitis. This low-dose regimen may improve the cost/benefit profile of rituximab therapy for MC.
Assuntos
Crioglobulinemia , Rituximab , Idoso , Feminino , Humanos , Masculino , Análise Custo-Benefício , Crioglobulinemia/complicações , Crioglobulinemia/tratamento farmacológico , Recidiva , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Vasculite/complicaçõesAssuntos
Crioglobulinemia/terapia , Hepacivirus/imunologia , Hepatite C Crônica/terapia , Imunoterapia , Vasculite/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Análise Custo-Benefício , Crioglobulinemia/economia , Crioglobulinemia/imunologia , Feminino , Hepatite C Crônica/imunologia , Hepatite C Crônica/mortalidade , Hospitalização/economia , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Taxa de Sobrevida , Vasculite/economia , Vasculite/imunologiaRESUMO
Eradication of hepatitis C virus (HCV) by antiviral therapy is the treatment of choice for mixed cryoglobulinemia secondary to this infection, but many patients fail to achieve sustained viral responses and need second-line treatments. Several studies have demonstrated that the infusion of the anti-CD20 monoclonal antibody rituximab is highly effective for refractory mixed cryoglobulinemia, with a clinical response in approximately 80% of patients, although the relapse rate is high. Virtually all published studies employed a rituximab dosage of 375mg/m(2) given four times, a schedule used for treating non-Hodgkin's lymphomas. Based on a prior pilot study, we designed a phase II single-arm two-stage study (EUDRACT n. 2008-000086-38) to evaluate the efficacy of a lower dosage of rituximab, 250mg/m(2) given twice, for refractory mixed cryoglobulinemia. We present here the preliminary results in the first 27 patients enrolled. The overall response rate in 24 evaluable patients was 79%, and the mean time to relapse was 6.5months, similar to the 6.7months reported in studies with high-dose rituximab. Side effects were comparable to those seen in patients treated with high-dose. Increase of HCV viral load, reported in some high-dose studies, was not observed in our patients. Low-dose rituximab may provide a more cost/effective and possibly safer alternative for treating refractory HCV-associated mixed cryoglobulinemia.