Reddy K Rajender, Shiffman Mitchell L, Morgan Timothy R, Zeuzem Stefan, Hadziyannis Stephanos, Hamzeh Fayez M, Wright Teresa L, Fried Michael
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Clin Gastroenterol Hepatol. 2007 Jan;5(1):124-9. doi: 10.1016/j.cgh.2006.10.008. Epub 2006 Dec 28.
BACKGROUND & AIMS: To maximize sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, treatment with pegylated interferon and ribavirin has been genotype-specific (1 vs non-1). We evaluated the effects of ribavirin and peginterferon alfa-2a dose reductions on SVR in patients infected with HCV genotype 1.
Data were pooled from 569 patients enrolled in 2 phase III trials of 48 weeks of treatment with peginterferon alfa-2a and ribavirin. All patients were evaluated for the effect of cumulative drug exposure on 4- and 12-week responses, and the 427 patients who completed treatment were evaluated for effect of drug exposure on SVR.
Of patients who completed treatment, more had reductions (< or =97% cumulative dose) of ribavirin than of peginterferon alfa-2a (43% vs 27%). Neither early virologic response nor SVR was affected adversely by ribavirin reductions when the cumulative ribavirin exposure was greater than 60%. The SVR was reduced significantly (P = .0006) in patients with less than the 60% cumulative ribavirin dose and was associated with prolonged periods of dose reduction, temporary interruptions, or premature cessation of ribavirin. Ribavirin dose reductions had minimal impact on SVR in patients who achieved rapid virologic response, defined as undetectable HCV RNA levels after 4 weeks, even when they received less than the 60% cumulative ribavirin dose. In contrast, SVR was reduced markedly in patients who had ribavirin dose reductions and did not achieve rapid virologic response.
Minor ribavirin dose reductions to manage adverse events do not appear to affect SVR adversely, unless cumulative exposure is less than 60%. Prospective studies, however, are required to establish the impact of ribavirin dose reduction on SVR.
为了使慢性丙型肝炎病毒（HCV）感染患者的持续病毒学应答（SVR）最大化，聚乙二醇化干扰素和利巴韦林的治疗方案已根据基因型进行了区分（1型与非1型）。我们评估了利巴韦林和聚乙二醇化干扰素α-2a剂量减少对HCV 1型感染患者SVR的影响。
汇总了569例参加两项用聚乙二醇化干扰素α-2a和利巴韦林进行48周治疗的III期试验患者的数据。评估所有患者累积药物暴露对4周和12周应答的影响，对完成治疗的427例患者评估药物暴露对SVR的影响。
在完成治疗的患者中，利巴韦林剂量减少（累积剂量≤97%）的患者多于聚乙二醇化干扰素α-2a剂量减少的患者（43%对27%）。当累积利巴韦林暴露大于60%时，利巴韦林剂量减少对早期病毒学应答和SVR均无不利影响。累积利巴韦林剂量低于60%的患者SVR显著降低（P = 0.0006），且与利巴韦林长时间剂量减少、暂时中断或提前停药有关。在实现快速病毒学应答（定义为4周后HCV RNA水平不可检测）的患者中，即使利巴韦林累积剂量低于60%，利巴韦林剂量减少对SVR的影响也最小。相比之下，利巴韦林剂量减少且未实现快速病毒学应答的患者SVR明显降低。
为应对不良事件而进行的小剂量利巴韦林减量似乎不会对SVR产生不利影响，除非累积暴露低于60%。然而，需要进行前瞻性研究来确定利巴韦林剂量减少对SVR的影响。
