Saadoun D, Resche-Rigon M, Sene D, Perard L, Karras A, Cacoub P
Pierre et Marie Curie-Paris 6, University 1, CNRS, UMR 7087, Paris, F-75013 France.
Ann Rheum Dis. 2008 Oct;67(10):1431-6. doi: 10.1136/ard.2007.081653. Epub 2008 Jan 4.
To report the results of a pilot study using rituximab combined with Peg-interferon (IFN) alpha2b-ribavirin in severe refractory hepatitis C virus (HCV) related mixed cryoglobulinaemia (MC) vasculitis.
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-IFNalpha2b (n = 6) plus ribavirin were included. They were treated with rituximab (375 mg/m2 intravenously weekly for 4 weeks) combined with Peg-IFNalpha2b (1.5 mug/kg per week subcutaneously) plus ribavirin (600-1200 mg/day orally) for 12 months.
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.
Rituximab combined with Peg-IFNalpha2b-ribavirin represents a safe and effective treatment option in severe refractory HCV-MC vasculitis.
报告一项初步研究的结果，该研究使用利妥昔单抗联合聚乙二醇干扰素（IFN）α2b-利巴韦林治疗严重难治性丙型肝炎病毒（HCV）相关混合性冷球蛋白血症（MC）血管炎。
纳入16例连续的严重HCV-MC血管炎患者，这些患者对先前使用标准（n = 10）或聚乙二醇IFNα2b（n = 6）加利巴韦林的联合治疗耐药（n = 11）或复发（n = 5）。他们接受利妥昔单抗（375 mg/m²静脉注射，每周一次，共4周）联合聚乙二醇IFNα2b（1.5 μg/kg每周皮下注射）加利巴韦林（600 - 1200 mg/天口服）治疗12个月。
15例患者（93.7%）显示临床改善，其中10例（62.5%）为临床完全缓解者（CR）。在所有临床CR患者中，HCV RNA和血清冷球蛋白均检测不到。所有患者均实现外周血B细胞耗竭（基线时CD19⁺细胞为111（标准差32）/mm³，在第四次输注利妥昔单抗后为2（2）/mm³），抗病毒治疗结束时开始恢复。与临床CR患者相比，部分缓解或无反应者在治疗前血管炎持续时间长3.6倍，早期病毒学反应率较低。治疗耐受性良好，无感染并发症。平均随访19.4（标准差3.6）个月后，2例患者出现临床复发，同时伴有HCV RNA和冷球蛋白再次出现以及B细胞数量增加。
利妥昔单抗联合聚乙二醇IFNα2b-利巴韦林是严重难治性HCV-MC血管炎的一种安全有效的治疗选择。
