Cheng S J, Bonis P A, Lau J, Pham N Q, Wong J B
Division of Clinical Decision Making, Informatics and Telemedicine, Department of Medicine, New England Medical Center Hospitals, Tufts University School of Medicine, Boston, MA, USA.
Hepatology. 2001 Jan;33(1):231-40. doi: 10.1053/jhep.2001.20675.
The efficacy of interferon (IFN) combined with ribavirin for the treatment of patients with hepatitis C who failed to respond to initial IFN therapy is not well established. The primary goal of this study was to perform a systematic review of the literature evaluating the efficacy of combination therapy in nonresponders. Studies were retrieved from MEDLINE, abstracts of scientific meetings, and review of the bibliographies of retrieved studies. Controlled trials were included in the primary analysis whereas uncontrolled trials and trials reported as abstracts were included for sensitivity analysis. The primary endpoints were biochemical and virologic response. A combined estimate of the odds ratio (OR) for each endpoint was obtained by using the random effects model. The number needed to treat (NNT) was calculated by taking the inverse of the pooled risk difference. Nine controlled trials (789 patients) were identified. Six months after treatment, the overall sustained biochemical and virologic responses to 24 weeks of combination therapy were 15.2% and 13.2% with a common OR of 3.8 (95% confidence interval [CI] 2.2-6.7) and 4.9 (95% CI 2.1-11.2) compared with patients treated with IFN monotherapy. The pooled risk difference for the sustained virologic response (SVR) to combination therapy was 7% (95% CI 2-13). The NNT was 14 (95% CI 8-50), suggesting that approximately 14 patients would need to be treated with 6 months of combination therapy for 1 patient to have a SVR. A number of variables were associated with a high response rate in individual studies. Sensitivity analysis of preliminary trials suggest a higher response rate with longer duration of therapy and non-type 1 genotypes.
干扰素（IFN）联合利巴韦林用于治疗对初始IFN治疗无反应的丙型肝炎患者的疗效尚未明确确立。本研究的主要目的是对评估联合治疗在无反应者中疗效的文献进行系统综述。研究从MEDLINE、科学会议摘要以及对检索到的研究的参考文献回顾中获取。主要分析纳入对照试验，而敏感性分析纳入非对照试验和以摘要形式报道的试验。主要终点为生化和病毒学反应。通过随机效应模型获得每个终点的合并比值比（OR）估计值。治疗所需人数（NNT）通过合并风险差的倒数计算得出。确定了9项对照试验（789例患者）。治疗6个月后，与接受IFN单药治疗的患者相比，联合治疗24周后的总体持续生化和病毒学反应分别为15.2%和13.2%，合并OR分别为3.8（95%置信区间[CI]2.2 - 6.7）和4.9（95%CI 2.1 - 11.2）。联合治疗的持续病毒学反应（SVR）的合并风险差为7%（95%CI 2 - 13）。NNT为14（95%CI 8 - 50），这表明大约14例患者需要接受6个月的联合治疗才能有1例实现SVR。在个别研究中，一些变量与高反应率相关。初步试验的敏感性分析表明，治疗时间更长和非1型基因型的反应率更高。
