Wang Zhitao, Ran Youbing, Fu Yihan, Sun Jing, Liu Yuanli
School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Infect Dis Poverty. 2025 Jul 25;14(1):75. doi: 10.1186/s40249-025-01344-2.
Despite price advantages, local direct-acting antiviral agents (DAAs) for hepatitis C (hep C) have not been widely used in China compared with the imported ones. There is no evidence on their relative efficacy and safety, nor whether the small market share of local DAAs was attributable to the potential differences.
This study systematically evaluated the efficacy and safety evidence of 5 local and 6 imported DAAs with valid Chinese registration numbers as of January 25, 2024. Meta-analyses, subgroup analyses and meta-regressions were performed to synthesize evidence and compared the outcomes by using the random-effects empirical Bayes model.
Nineteen randomized controlled trials and 82 single-arm trials (SATs) were included. The results demonstrated no statistically significant difference in 12-week sustained virological response [0.97, (95% confidence interval (CI) 0.95, 0.99) vs 0.96, (95% CI: 0.94, 0.98), P = 0.21], relapse [0.02, (95% CI: 0.01, 0.04) vs 0.02, (95% CI: 0.01, 0.03), P = 0.65], virological breakthrough [0.003, (95% CI: < 0.001, 0.02) vs 0.0000002, (95% CI: < 0.001, 0.0006), P = 0.51] and serious adverse events (SAEs) [0.04, (95% CI: 0.03, 0.06) vs 0.03, (95% CI: 0.02, 0.03), P = 0.12] between local and imported DAAs. By controlling for ethnicities of patients in multiple meta-regression, the local DAAs had a 33.7% higher rate of adverse events (AEs) [0.337, (95% CI: 0.188, 0.486), P < 0.001]. No statistically significant difference was found in the interaction test between local and imported pan-genotypic DAAs regarding the rate of AEs [0.72, (95% CI: 0.64, 0.79) vs 0.73, (95% CI: 0.65, 0.50), P = 0.81].
Current evidence demonstrates no statistically significant differences in efficacy and SAEs between local and imported DAAs. Given that simplified pan-genotypic DAA regimens are now standard care, local pan-genotypic DAAs hold potential to increase hepatitis C virus treatment rates in China. It is critical for local DAA developers to generate more evidence with expanded patient population in terms of age, treatment experience and genotype of hepatitis C virus, conducting head-to-head studies directly comparing the efficacy and safety. Clinical and policy decision-making should be adaptive and evolve as new evidence is generated.
尽管具有价格优势，但与进口的丙型肝炎直接抗病毒药物（DAAs）相比，国产DAAs在中国尚未得到广泛应用。目前尚无关于其相对疗效和安全性的证据，也不清楚国产DAAs市场份额较小是否归因于潜在差异。
本研究系统评价了截至2024年1月25日具有有效中国注册文号的5种国产和6种进口DAAs的疗效和安全性证据。进行荟萃分析、亚组分析和meta回归以综合证据，并使用随机效应经验贝叶斯模型比较结果。
纳入了19项随机对照试验和82项单臂试验（SATs）。结果显示，国产和进口DAAs在12周持续病毒学应答[0.97，（95%置信区间（CI）0.95，0.99）对0.96，（95%CI：0.94，0.98），P = 0.21]、复发[0.02，（95%CI：0.01，0.04）对0.02，（95%CI：0.01，0.03），P = 0.65]、病毒学突破[0.003，（95%CI：<0.001，0.02）对0.0000002，（95%CI：<0.001，0.0006），P = 0.51]和严重不良事件（SAEs）[0.04，（95%CI：0.03，0.06）对0.03，（95%CI：0.02，0.03），P = 0.12]方面无统计学显著差异。通过在多重meta回归中控制患者种族，国产DAAs的不良事件（AEs）发生率高33.7%[0.337，（95%CI：0.188，0.486），P < 0.001]。在国产和进口泛基因型DAAs之间关于AEs发生率的交互检验中未发现统计学显著差异[0.72，（95%CI：0.64，0.79）对0.73，（95%CI：0.65，0.50），P = 0.81]。
目前证据表明国产和进口DAAs在疗效和SAEs方面无统计学显著差异。鉴于简化的泛基因型DAA方案目前是标准治疗，国产泛基因型DAAs有潜力提高中国丙型肝炎病毒治疗率。国产DAA研发者至关重要的是在年龄、治疗经验和丙型肝炎病毒基因型等更广泛患者群体中产生更多证据，开展直接比较疗效和安全性的头对头研究。临床和政策决策应具有适应性，并随着新证据的产生而发展。
