Younossi Zobair M, Stepanova Maria, Sulkowski Mark, Foster Graham R, Reau Nancy, Mangia Alessandra, Patel Keyur, Bräu Norbert, Roberts Stuart K, Afdhal Nezam, Nader Fatema, Henry Linda, Hunt Sharon
Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.
Center for Outcomes Research in Liver Disease, Washington D.C.
Clin Infect Dis. 2016 Oct 15;63(8):1042-1048. doi: 10.1093/cid/ciw496. Epub 2016 Jul 20.
Until recently, the approved treatment regimens for patients with hepatitis C virus (HCV) genotypes (GTs) 2 and 3 contain sofosbuvir (SOF) and ribavirin (RBV) for 12 or 24 weeks. The impact of RBV-free pan-genotypic regimen with SOF and velpatasvir (SOF/VEL) on patient-reported outcomes (PROs) of patients with genotype 2 and 3 has not been described.
PROs data were collected from participants of ASTRAL-2 and ASTRAL-3 studies before, during, and after treatment using 4 PRO instruments (Short Form-36, Chronic Liver Disease Questionnaire-HCV, Functional Assessment of Chronic Illness Therapy-Fatigue, and Work Productivity and Activity Index: Specific Health Problem), and compared between the SOF/VEL and SOF + RBV groups.
A total of 818 HCV patients were included: 78% treatment naive, 25% cirrhosis. The rates of nearly all adverse events were lower in the RBV-free SOF/VEL group (all P < .03). The SOF/VEL group also experienced improvement of their PROs by treatment week 4 (+1.8% on average across all PROs), which continued throughout treatment (+4.1%) and post-treatment (+5.5%). In contrast, those in the SOF + RBV group had a modest decline in their PROs starting at treatment week 4 (up to -3.7%), which lasted until the end of treatment (up to -6.4%). In multiple regression analysis, the association of a treatment regimen with end-of-treatment PROs was significant for nearly all PROs; the average beta was +5.0% for the use of SOF/VEL (reference: SOF + RBV).
Patients receiving ribavirin-free SOF/VEL reported significantly better PRO scores during treatment compared with those receiving the RBV-containing regimen. Furthermore, the interferon- and ribavirin-free SOF/VEL regimen resulted in a rapid improvement of PROs in HCV GTs 2 and 3 patients during treatment and after achieving sustained virologic response.
直到最近，丙型肝炎病毒（HCV）基因2型和3型患者的获批治疗方案都包含索磷布韦（SOF）和利巴韦林（RBV），疗程为12周或24周。不含RBV的索磷布韦和维帕他韦泛基因型方案（SOF/VEL）对基因2型和3型患者报告结局（PRO）的影响尚未见报道。
使用4种PRO工具（简明健康状况调查问卷36项简短形式、丙型肝炎慢性肝病问卷、慢性病治疗功能评估-疲劳以及工作效率和活动指数：特定健康问题），在治疗前、治疗期间和治疗后从ASTRAL-2和ASTRAL-3研究的参与者中收集PRO数据，并在SOF/VEL组和SOF + RBV组之间进行比较。
共纳入818例HCV患者：78%为初治患者，25%有肝硬化。不含RBV的SOF/VEL组几乎所有不良事件的发生率均较低（所有P <.03）。SOF/VEL组在治疗第4周时PRO也有改善（所有PRO平均提高1.8%），在整个治疗期间（提高4.1%）和治疗后（提高5.5%）持续改善。相比之下，SOF + RBV组患者的PRO从治疗第4周开始有适度下降（降幅高达3.7%），一直持续到治疗结束（降幅高达6.4%）。在多元回归分析中，治疗方案与治疗结束时的PRO之间的关联对几乎所有PRO均有显著意义；使用SOF/VEL时的平均β值为+5.0%（参考：SOF + RBV）。
与接受含RBV方案的患者相比，接受不含利巴韦林的SOF/VEL治疗的患者在治疗期间报告的PRO评分显著更好。此外，不含干扰素和利巴韦林的SOF/VEL方案在治疗期间以及实现持续病毒学应答后，使HCV基因2型和3型患者的PRO迅速改善。
