Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension

Robert S Brown Jr, Michelle A Collins, Simone I Strasser, Amanda Emmett, Andrew S Topp, Margaret Burroughs, Rosa Ferreira, Jordan J Feld, Robert S Brown Jr, Michelle A Collins, Simone I Strasser, Amanda Emmett, Andrew S Topp, Margaret Burroughs, Rosa Ferreira, Jordan J Feld

Abstract

Introduction: High efficacy and safety of 8-week glecaprevir/pibrentasvir (G/P) therapy was seen in hepatitis C (HCV)-infected, treatment-naïve (TN), compensated cirrhosis (CC) patients in EXPEDITION-8. To provide further understanding of the efficacy of G/P treatment in HCV-infected TN patients with CC and clinical evidence of portal hypertension (PHT), this analysis focused on differences in sustained virologic response at post-treatment week 12 (SVR12) between 8-week and 12-week G/P treatment groups in patients with PHT, and on differences in safety outcomes between PHT and non-PHT groups.

Methods: Data were derived from an ad hoc subgroup analysis of the EXPEDITION-8 study for patients receiving 8 weeks of G/P therapy, and pooled patient-level data from nine clinical studies for patients receiving 12 weeks of therapy. Evidence of PHT included at least one of the following at baseline: FibroScan ≥ 20 kPa, platelets < 100 × 109/L, or medical history consistent with PHT. The primary efficacy endpoint was SVR12; adverse events (AEs) consistent with hepatic decompensation were assessed.

Results: PHT was identified in 60.6% (208/343) and 57.1% (224/392) of the 8- and 12-week groups, respectively. For those with PHT, SVR12 was 97.6% (203/208) and 98.7% (221/224) with 8- and 12-week treatment, respectively (intention-to-treat population). For those without PHT, 97.8% (132/135) in the 8-week group and 97.6% (164/168) in the 12-week group achieved SVR12. Eight patients with PHT, and seven without, did not achieve SVR12. Similar rates of AEs were observed in the PHT and non-PHT groups. Three cases of hepatic decompensation in the PHT group, unrelated to G/P according to the investigators, were reported.

Conclusion: G/P treatment for 8 or 12 weeks was equally efficacious in HCV patients with features of PHT. Safety outcomes were similar between PHT and non-PHT groups, with G/P treatment well tolerated across groups. NCTS: NCT03089944, NCT02642432, NCT02738138, NCT02243293, NCT02651194, NCT03235349, NCT02707952, NCT02966795, NCT03069365, NCT03219216.

Keywords: Glecaprevir; Hepatitis C; Pibrentasvir; Portal Hypertension; Sustained Virologic Response.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Percentage of patients who achieved SVR12 receiving 8 or 12 weeks of G/P therapy (ITT analysis); % SVR12 ± 95% confidence interval. G/P glecaprevir/pibrentasvir, ITT intention-to-treat, PHT portal hypertension, SVR12 sustained virologic response at post-treatment week 12

References

    1. World Health Organization . Global progress report on hiv, viral hepatitis and sexually transmitted infections. Geneva: WHO; 2021.
    1. Akinyemiju T, Abera S, Ahmed M, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3(12):1683–1691. doi: 10.1001/jamaoncol.2017.3055.
    1. Liu Z, Jiang Y, Yuan H, et al. The trends in incidence of primary liver cancer caused by specific etiologies: results from the global burden of disease study 2016 and implications for liver cancer prevention. J Hepatol. 2019;70(4):674–683. doi: 10.1016/j.jhep.2018.12.001.
    1. de Franchis R. Expanding consensus in portal hypertension: report of the baveno vi consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–752. doi: 10.1016/j.jhep.2015.05.022.
    1. European Association for the Study of the Liver Easl recommendations on treatment of hepatitis c: final update of the series. J Hepatol. 2020;73(5):1170–1218. doi: 10.1016/j.jhep.2020.08.018.
    1. Brown RS, Jr, Buti M, Rodrigues L, et al. Glecaprevir/pibrentasvir for 8 weeks in treatment-naive patients with chronic hcv genotypes 1–6 and compensated cirrhosis: the expedition-8 trial. J Hepatol. 2020;72(3):441–449. doi: 10.1016/j.jhep.2019.10.020.
    1. Zuckerman E, Gutierrez JA, Dylla DE, et al. Eight weeks of treatment with glecaprevir/pibrentasvir is safe and efficacious in an integrated analysis of treatment-naïve patients with hepatitis c virus infection. Clin Gastroenterol Hepatol. 2020;18(11):2544–53.e6. doi: 10.1016/j.cgh.2020.06.044.
    1. Asselah T, Lee SS, Yao BB, et al. Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic hepatitis c virus genotype 5 or 6 infection (endurance-5,6): an open-label, multicentre, phase 3b trial. Lancet Gastroenterol Hepatol. 2019;4(1):45–51. doi: 10.1016/S2468-1253(18)30341-8.
    1. Rockstroh JK, Lacombe K, Viani RM, et al. Efficacy and safety of glecaprevir/pibrentasvir in patients coinfected with hepatitis c virus and human immunodeficiency virus type 1: the expedition-2 study. Clin Infect Dis. 2018;67(7):1010–1017. doi: 10.1093/cid/ciy220.
    1. Wei L, Wang G, Alami NN, et al. Glecaprevir-pibrentasvir to treat chronic hepatitis c virus infection in asia: Two multicentre, phase 3 studies—a randomised, double-blind study (voyage-1) and an open-label, single-arm study (voyage-2) Lancet Gastroenterol Hepatol. 2020;5(9):839–849. doi: 10.1016/S2468-1253(20)30086-8.
    1. Lampertico P, Mauss S, Persico M, et al. Real-world clinical practice use of 8-week glecaprevir/pibrentasvir in treatment-naïve patients with compensated cirrhosis. Adv Ther. 2020;37(9):4033–4042. doi: 10.1007/s12325-020-01449-0.
    1. Abbvie. Maviret [Summary of Product Characteristics]. 2021 [cited 2021 September 10]. Available from: .
    1. AbbVie. Mavyret. North Chicago, IL; 2021.
    1. Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis c virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (expedition-1): A single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17(10):1062–1068. doi: 10.1016/S1473-3099(17)30496-6.
    1. Wyles D, Poordad F, Wang S, et al. Glecaprevir/pibrentasvir for hepatitis c virus genotype 3 patients with cirrhosis and/or prior treatment experience: a partially randomized phase 3 clinical trial. Hepatology. 2018;67(2):514–523. doi: 10.1002/hep.29541.
    1. Gane E, Lawitz E, Pugatch D, et al. Glecaprevir and pibrentasvir in patients with hcv and severe renal impairment. N Engl J Med. 2017;377(15):1448–1455. doi: 10.1056/NEJMoa1704053.
    1. Toyoda H, Chayama K, Suzuki F, et al. Efficacy and safety of glecaprevir/pibrentasvir in japanese patients with chronic genotype 2 hepatitis c virus infection. Hepatology. 2018;67(2):505–513. doi: 10.1002/hep.29510.
    1. Lawitz E, Flisiak R, Abunimeh M, et al. Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic hcv infection. Liver Int. 2020;40(5):1032–1041. doi: 10.1111/liv.14320.
    1. Peribanez-Gonzalez M, Cheinquer H, Rodrigues L, et al. Efficacy and safety of glecaprevir/pibrentasvir in treatment-naive adults with chronic hepatitis c virus genotypes 1–6 in brazil. Ann Hepatol. 2021;20:100257. doi: 10.1016/j.aohep.2020.09.002.
    1. Forns X, Feld JJ, Dylla DE, et al. Safety of patients with hepatitis c virus treated with glecaprevir/pibrentasvir from clinical trials and real-world cohorts. Adv Ther. 2021;38(6):3409–3426. doi: 10.1007/s12325-021-01753-3.
    1. Jonas MM, Rhee S, Kelly DA, et al. Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic hcv: Part 2 of the dora study. Hepatology. 2021;74(1):19–27. doi: 10.1002/hep.31841.
    1. Klinker H, Naumann U, Rossle M, et al. Glecaprevir/pibrentasvir for 8 weeks in patients with compensated cirrhosis: safety and effectiveness data from the german hepatitis c-registry. Liver Int. 2021;41(7):1518–1522. doi: 10.1111/liv.14937.
    1. Su PY, Chen YY, Lai JH, et al. Real-world experience of chronic hepatitis c-related compensated liver cirrhosis treated with glecaprevir/pibrentasvir: a multicenter retrospective study. J Clin Med. 2021;10(22):5236. doi: 10.3390/jcm10225236.
    1. Wedemeyer H, Erren P, Naumann U, et al. Glecaprevir/pibrentasvir is safe and effective in hepatitis c patients with cirrhosis: real-world data from the german hepatitis c-registry. Liver Int. 2021;41(5):949–955. doi: 10.1111/liv.14829.
    1. Zarebska-Michaluk D, Jaroszewicz J, Parfieniuk-Kowerda A, et al. Effectiveness and safety of pangenotypic regimens in the most difficult to treat population of genotype 3 hcv infected cirrhotics. J Clin Med. 2021;10(15):3280. doi: 10.3390/jcm10153280.
    1. Ferenci P. Are all cirrhotic patients equal? J Hepatol. 2020;72(3):389–390. doi: 10.1016/j.jhep.2019.10.022.

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