比较西甲匹韦与特拉匹韦联合聚乙二醇干扰素及利巴韦林的三联方案治疗慢性丙型肝炎基因1型患者的meta分析

Comparison of simeprevir versus telaprevir plus pegylated interferon alfa and ribavirin in patients with hepatitis C virus genotype 1 infection a meta-analysis

目的比较西甲匹韦（simeprevir，SMV）和特拉匹韦（telaprevir，TVR）联合聚乙二醇干搠素及利巴韦林的三联方案治疗慢性丙型肝炎基因1型患者的有效性和安全性。方法通过在线检索参个电子数据库来确定相关的研究文献，选取以治疗结束后12周持续病毒学应答（sustainedvirologicresponse，SVRl2）率和SVR24率作为有效性结局指标，与将治疗相关的不良反应、因药物相关不良反应导致停药，以及总的停止治疗发生率作为安全性结局指标。此外，根据既往治疗情况将纳入患者分成雾个亚组，进一步分析两种治疗方案在各类患者中的治疗效果。所有统计分析均在RevMan5．3软件咔进行。采用Jajad评分量表和Newcastle-Ottawas评分量表对纳入文章进行质量评估。方法本研究掣纳入了5篇文章，共计1666例基因1型患者。SMV组的平均SVRl2率为67．6％，TVR组为68．3％比较差异无统计学意义（OR=0．95，95％CI：0．76～1．18，P=0．65），研究间无明显异质性（P=0．84,I2=0%）；SMV组平均SVR24率为78％，低于TVR组的84％，但差异无统计学意义（OR=0．7195％CI：0．42～1．20，P=0.20），研究间也不存在异质性（P=0.69，I2=0％）。亚组分析结果显示SMV和TvR为基础的三联方案对初始治疗、部分应答、完全无应答，以及复发患者的治疗效果差异蜷无统计学意义（均P〉0．05）。但合并分析发现，以上两种三联方案均对初始治疗的患者最有彭（SMV85．7％，TvR85．6％）。SMV组贫血发生率显著高于TVR组（0R=0．30，P〈O．01）。对停止滩疗的发生率分析发现，SMV和TVR组总的停止治疗发生率间差异无统计学意义（OR=0．48，P=0．12）。方法SMV三联治疗方案的有效性类似于TVR三联治疗方案。但SMV组与TVR组相比确更好的耐受性和更低的贫血及因药物相关不良反应事件导致停药的发生率。

Objective To compare the efficacy and safety of simeprevir-based （SMV） or telaprevir- based （TVR） triple therapy I-SMV ＋ Pegylated interferon alfa （PegIFNa） and ribavirin （RBV） versus TVR ＋ PegIFNa and RBV] in patients with hepatitis C virus （HCV） genotype 1 infection. Methods A systematic literature searching was conducted in multiple online databases to identify relevant studies. The sustained virologic response rate at 12 （SVR12） and 24 weeks （SVR24） after end of the treatment were used as the efficacy endpoints. The rate of treatment related adverse events （AEs）, discontinuation due to AEs and overall treatment discontinuation were used as safety endpoints. Patients were divided into multiple subgroups according to the previous treatment history to further compare the efficacy of the two treatment regimen. Statistical analyses were performed using the RevMan 5.3 software. The Jajad score scale and the Newcastle-Ottawa scate were employed to evaluate the quality of included studies. Results A total of 5 clinical studies including 1666 HCV genotype 1 patients were included in this study. The pooled results showed that SVR12 rates in SMV group and TVR group were 67. 6% and 68. 3%/00, respectively. There was no significant difference in overall SVR12 rate between SMV and TVR groups （OR=O. 95, 95% CI： O. 76=1. 18, P=0. 65）. There was no significant heterogeneity among studies （P=0.84,I2= 0%）. For SVR24 rate, the average SVR24 rate in SMV group was 78%, which was lower than that in TVR group of 84%. However, there was no significant difference in overall SVR24 rate between SMV and TVR groups （OR=0.71, 95% CI： O. 42.—1.20, P=0.20）. Meanwhile, there was no significant heterogeneity among studies （P=0. 69, 12= 0%）. The subgroup analysis also showed that there was no significant difference in efficacy between SMV and TVR-based triple therapy for treatmentnative patients, prior partial response, relapse, and prior null response patients （all P%0.05）. However, the pooled analysis indicated that both SMV-based and TVR-based triple therapies were most effective for the treatment naive patients（SMV： 85.7 %, TVR ： 85.6 %）. For the safety endpoints, the incidence rate of anemia was significant lower in SMV group compared to TVR group （OR=0.30, P〈0. 001）. For the rate of overall treatment discontinuation, there was no statistically significant difference between SMV and TVR group （OR=0.48, P=0.12）. Conclusions This meta-analysis suggests that the efficacy of SMVbased triple therapy is non-inferior to TVR-based triple therapy. However, the SMV-based triple therapy is more tolerable and has a lower incident rate of anemia and discontinuation due to AEs compared to TVRbased triple therapy.