Lo Re Vincent, Amorosa Valerianna K, Localio A Russell, O'Flynn Rose, Teal Valerie, Dorey-Stein Zachariah, Kostman Jay R, Gross Robert
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, 423 Guardian Dr., Philadelphia, PA 19104-6021, USA.
Clin Infect Dis. 2009 Jan 15;48(2):186-93. doi: 10.1086/595685.
Suboptimal drug exposure attributable to physician-directed dosage reductions of pegylated interferon and/or ribavirin are associated with decreased sustained virologic response rates. However, data are limited with regard to suboptimal drug exposure that is attributable to missed doses by patients with chronic hepatitis C virus (HCV) infection. We examined the relationship between adherence to pegylated interferon and ribavirin therapy, measured by pharmacy refill, and HCV suppression during the initial 12 weeks of therapy.
We conducted a cohort study involving 188 patients with chronic HCV infection who were treated with pegylated interferon plus ribavirin. Adherence was calculated using pharmacy refill data and could exceed 100%. The primary outcome was decrease in HCV load at 12 weeks; early virologic response was a secondary outcome. Mixed-effects regression models estimated the association between adherence and HCV suppression during the initial 12 weeks. Subanalyses were performed among patients who received optimal weight-based dosages.
The mean decrease in HCV load at 12 weeks was 0.66 log IU/mL greater for patients with > or =85% adherence than for those with <85% adherence (3.23 vs. 2.57 log IU/mL; P = .04). When patients who received a suboptimal ribavirin dosage were excluded, the decrease in viral load was 1.00 log IU/mL greater for persons with > or =85% adherence (3.32 vs. 2.32 log IU/mL; P = .01). Early virologic response was more common among patients with > or =85% adherence than it was among those with <85% adherence to treatment with pegylated interferon (73% vs. 29%; P = .02) and ribavirin (73% vs. 55%; P = .08).
Adherence of > or =85% to pegylated interferon and ribavirin treatment was associated with increased HCV suppression. Decreases in HCV load became greater when patients with > or =85% adherence to their regimen continued to receive their recommended weight-based ribavirin dosage.
聚乙二醇化干扰素和/或利巴韦林因医生指导下的剂量减少导致药物暴露不足,这与持续病毒学应答率降低有关。然而,关于慢性丙型肝炎病毒(HCV)感染患者漏服药物导致的药物暴露不足的数据有限。我们研究了通过药房配药衡量的聚乙二醇化干扰素和利巴韦林治疗依从性与治疗最初12周内HCV抑制之间的关系。
我们进行了一项队列研究,纳入188例接受聚乙二醇化干扰素加利巴韦林治疗的慢性HCV感染患者。使用药房配药数据计算依从性,依从性可能超过100%。主要结局是12周时HCV载量的下降;早期病毒学应答是次要结局。混合效应回归模型估计了最初12周内依从性与HCV抑制之间的关联。在接受基于体重的最佳剂量的患者中进行了亚组分析。
依从性≥85%的患者在12周时HCV载量的平均下降幅度比依从性<85%的患者大0.66 log IU/mL(3.23对2.57 log IU/mL;P = 0.04)。排除接受次优利巴韦林剂量的患者后,依从性≥85%的患者病毒载量下降幅度大1.00 log IU/mL(3.32对2.32 log IU/mL;P = 0.01)。在聚乙二醇化干扰素治疗依从性≥85%的患者中,早期病毒学应答比依从性<85%的患者更常见(73%对29%;P = 0.02),在利巴韦林治疗中也是如此(73%对55%;P = 0.08)。
聚乙二醇化干扰素和利巴韦林治疗的依从性≥85%与HCV抑制增加有关。当依从性≥85%的患者继续接受推荐的基于体重的利巴韦林剂量时,HCV载量的下降幅度更大。