Ferreira V L, Assis Jarek N A, Tonin F S, Borba H H L, Wiens A, Pontarolo R
Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
J Clin Pharm Ther. 2016 Oct;41(5):478-85. doi: 10.1111/jcpt.12426. Epub 2016 Jul 21.
Interferon-free (IFN-free) therapies for hepatitis C virus (HCV) have been developed to provide more effective, tolerable and safer therapeutic strategies. To date, no network meta-analysis (NMA) evaluating the safety profile of these regimens has been performed. This systematic review and NMA aimed to evaluate safety outcomes of IFN-free treatment options for chronic hepatitis C.
A systematic review was performed according to PRISMA and Cochrane recommendations. A literature search was conducted in PubMed/Medline, Scopus, Cochrane Library, International Pharmaceutical Abstracts and Web of Science electronic databases and included only randomized clinical trials that provided safety outcomes of interest of evaluated second-generation direct-acting antivirals: incidence of any adverse events (AEs) and serious AE. NMA allowed estimating probability for the relative safety of the interventions. A consistency model was used to draw conclusions about relative safety of treatments, presented as odds ratio (OR) and corresponding 95% credible interval (CrI).
Fifty-one clinical trials were included (13 089 participants). Most participants had hepatitis C genotype 1 virus (76%) and were treated for 12 weeks. Two NMAs were built to investigate the incidence of AEs and serious AEs, comparing 13 and 10 IFN-free treatment options, respectively. For the outcome incidence of AEs, few significant differences were observed, which were explained by the presence of RBV. Elbasvir with grazoprevir and placebo were both safer than ombitasvir in combination with paritaprevir, ritonavir, daclatasvir plus RBV [ORs with 95% Crl of 4·09 (1·17-14·09) and 2·40 (1·19-4·77), respectively] and sofosbuvir with RBV [ORs with 95% Crl of 0·22 (0·07-0·72) and 2·69 (1·53-4·80), respectively]. Furthermore, elbasvir with grazoprevir was safer than sofosbuvir used with velpatasvir and RBV [OR 0·19 (95% CrI 0·03-0·98)]; ombitasvir in combination with paritaprevir, ritonavir, daclatasvir was safer than the same therapy but combined with RBV [OR 2·14 (95% CrI 1·09-4·44)]; and sofosbuvir used with velpatasvir was safer than sofosbuvir with RBV [OR 2·07 (95% CrI 1·13-3·79)]. Elbasvir with grazoprevir (50%) followed by placebo (28%) had the highest probabilities of less AEs. No significant differences were observed for serious AE outcomes.
This meta-analysis included a large number of therapies. Small differences were observed in any AEs, but not in serious AEs.
已开发出丙型肝炎病毒（HCV）的无干扰素（IFN-free）疗法，以提供更有效、可耐受且更安全的治疗策略。迄今为止，尚未进行评估这些治疗方案安全性的网状Meta分析（NMA）。本系统评价和NMA旨在评估慢性丙型肝炎无干扰素治疗方案的安全性结局。
根据PRISMA和Cochrane推荐进行系统评价。在PubMed/Medline、Scopus、Cochrane图书馆、国际药学文摘和科学网电子数据库中进行文献检索，仅纳入提供了所评估的第二代直接作用抗病毒药物感兴趣的安全性结局的随机临床试验：任何不良事件（AE）和严重AE的发生率。NMA用于估计干预措施相对安全性的概率。使用一致性模型得出关于治疗相对安全性的结论，以比值比（OR）和相应的95%可信区间（CrI）表示。
纳入51项临床试验（13089名参与者）。大多数参与者感染丙型肝炎病毒1型（76%），治疗12周。构建了两项NMA以研究AE和严重AE的发生率，分别比较了13种和10种无干扰素治疗方案。对于AE发生率，观察到的显著差异较少，这可由利巴韦林（RBV）的存在来解释。艾尔巴韦与格拉瑞韦及安慰剂均比奥比他韦与帕利哌韦、利托那韦、达卡他韦加RBV更安全[OR及95%CrI分别为4.09（1.17 - 14.09）和2.40（1.19 - 4.77）]，以及索磷布韦与RBV[OR及95%CrI分别为0.22（0.07 - 0.72）和2.69（1.53 - 4.80）]。此外，艾尔巴韦与格拉瑞韦比索磷布韦与维帕他韦及RBV更安全[OR 0.19（95%CrI 0.03 - 0.98）]；奥比他韦与帕利哌韦、利托那韦、达卡他韦联合使用比相同疗法但联合RBV更安全[OR 2.14（95%CrI 1.09 - 4.44）]；索磷布韦与维帕他韦比索磷布韦与RBV更安全[OR 2.07（95%CrI 1.13 - 3.79）]。艾尔巴韦与格拉瑞韦（50%）其次是安慰剂（28%）发生较少AE的概率最高。严重AE结局未观察到显著差异。
本Meta分析纳入了大量治疗方法。在任何AE方面观察到的差异较小，但在严重AE方面未观察到差异。
