Department of Internal Medicine, Assistance Publique-Hopitaux de Paris, Groupe Hospitalier Pitié-Salpétrière, Paris, France.
Blood. 2010 Jul 22;116(3):326-34; quiz 504-5. doi: 10.1182/blood-2009-10-248518. Epub 2010 May 3.
Treatment of hepatitis C (HCV)-mixed cryoglobulinemia (MC) may target either the viral trigger (HCV) or the downstream B-cell clonal expansion. Prospective cohort study of 38 HCV-MC patients who received a combination of rituximab (375 mg/m(2)) once a week for 1 month followed by Peg-interferon-alpha (Peg-IFN-alpha; 2a, 180 microg or 2b, 1.5 microg/kg) weekly plus ribavirin (600-1200 mg) daily for 48 weeks were compared with 55 HCV-MC patients treated by Peg-IFN-alpha/ribavirin with the same modalities. In the whole population of HCV-MC patients (n = 93), a complete clinical response was achieved in 73.1% (68 of 93), cryoglobulin clearance in 52.7% (49 of 93), and a sustained virologic response in 59.1% (55 of 93). Compared with Peg-IFN-alpha/ribavirin, rituximab plus Peg-IFN-alpha/ribavirin-treated patients had a shorter time to clinical remission (5.4 +/- 4 vs 8.4 +/- 4.7 months, P = .004), better renal response rates (80.9% vs 40% of complete response, P = .040), and higher rates of cryoglobulin clearance (68.4% vs 43.6%, P = .001) and clonal VH1-69(+) B-cell suppression (P < .01). Treatment was well tolerated with 11% of discontinuation resulting from antiviral therapy and no worsening of HCV RNA under rituximab. Our findings indicate that rituximab combined with Peg-IFN-alpha/ribavirin is well tolerated and more effective than Peg-IFN-alpha/ribavirin in HCV-MC.
治疗丙型肝炎(HCV)-混合性冷球蛋白血症(MC)的方法可以针对病毒触发因素(HCV)或下游 B 细胞克隆扩增。对 38 例接受利妥昔单抗(375mg/m²)每周 1 次,连续 1 个月,然后每周给予聚乙二醇干扰素-α(Peg-IFN-α;2a,180μg或 2b,1.5μg/kg)联合利巴韦林(600-1200mg)每日治疗的 HCV-MC 患者进行了前瞻性队列研究,与接受相同方法的 Peg-IFN-α/利巴韦林治疗的 55 例 HCV-MC 患者进行了比较。在 HCV-MC 患者的整个人群(n=93)中,73.1%(93 例中的 68 例)获得完全临床缓解,52.7%(93 例中的 49 例)清除冷球蛋白,59.1%(93 例中的 55 例)获得持续病毒学应答。与 Peg-IFN-α/利巴韦林相比,利妥昔单抗联合 Peg-IFN-α/利巴韦林治疗的患者达到临床缓解的时间更短(5.4+/-4 个月与 8.4+/-4.7 个月,P=0.004),肾脏反应率更高(完全缓解的 80.9%与 40%,P=0.040),冷球蛋白清除率更高(68.4%与 43.6%,P=0.001)和 VH1-69(+)B 细胞克隆抑制率更高(P<0.01)。利妥昔单抗治疗的耐受性良好,抗病毒治疗导致 11%的患者停药,利妥昔单抗治疗后 HCV RNA 无恶化。我们的研究结果表明,利妥昔单抗联合 Peg-IFN-α/利巴韦林治疗 HCV-MC 的疗效优于 Peg-IFN-α/利巴韦林,且耐受性良好。