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Medline ® Abstracts for References 19-22

of 'What's new in gastroenterology and hepatology'

Puoti M, Foster GR, Wang S, et al. High SVR Rates With Eight and Twelve Weeks of Pangenotypic Glecaprevir/Pibrentasvir: Integrated Efficacy Analysis of Genotype 1-6 Patients Without Cirrhosis. Presented at the 52nd Annual Meeting of the European Association for the Study of the Liver (EASL), Amsterdam, The Netherlands, April 19-23, 2017.
no abstract available
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.
Forns X, Lee SS, Valdes J, Lens S, Ghalib R, Aguilar H, Felizarta F, Hassanein T, Hinrichsen H, Rincon D, Morillas R, Zeuzem S, Horsmans Y, Nelson DR, Yu Y, Krishnan P, Lin CW, Kort JJ, Mensa FJ
Lancet Infect Dis. 2017;17(10):1062. Epub 2017 Aug 14.
BACKGROUND: The once-daily, ribavirin-free, pangenotypic, direct-acting antiviral regimen, glecaprevir coformulated with pibrentasvir, has shown high rates of sustained virological response in phase 2 and 3 studies. We aimed to assess the efficacy and safety of 12 weeks of coformulated glecaprevir and pibrentasvir in patients with hepatitis C virus (HCV) infection and compensated cirrhosis.
METHODS: We did this single-arm, open-label, multicentre phase 3 study at 40 sites in Belgium, Canada, Germany, South Africa, Spain, and the USA. We enrolled patients aged 18 years or older with HCV genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. Patients were either HCV treatment-naive or had not responded to treatment with interferon or pegylated interferon with or without ribavirin, or sofosbuvir plus ribavirin with or without pegylated interferon. Oral glecaprevir (300 mg) coformulated with pibrentasvir (120 mg) was administered once daily for 12 weeks. Theprimary efficacy endpoint was sustained virological response at post-treatment week 12 (HCV RNA<15 IU/mL). We assessed efficacy and safety in all patients who received at least one dose of study drug (intention-to-treat population). This study is registered with ClinicalTrials.gov, number NCT02642432.
FINDINGS: Between Dec 7, 2015, and May 4, 2016, we enrolled 146 patients with compensated cirrhosis, of whom 48 (33%) had genotype 1a HCV infection, 39 (27%) had genotype 1b infection, 34 (23%) had genotype 2 infection, 16 (11%) had genotype 4 infection, two (1%) had genotype 5 infection, and seven (5%) had genotype 6 infection. 12 weeks after treatment, 145 patients (99%, 95% CI 98-100) achieved sustained virological response, with one (1%) relapse at post-treatment week 8. We recorded 101 (69%) adverse events, of which 65 (64%) were mild. The most common adverse events were fatigue (n=28 [19%]) and headache (n=20 [14%]). 11 (8%) patients had serious adverse events, none of which were deemed related to study drugs. No patients had elevations in alanine aminotransferase and no patients prematurely discontinued treatment because of adverse events.
INTERPRETATION: Our results show that 99% of patients treated with once-daily glecaprevir plus pibrentasvir achieved a sustained virological response at 12 weeks. Furthermore, this drug regimen had a favourable safety profile in previously treated or untreated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. These findings could help simplify treatment algorithms and reduce treatment burden.
Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain. Electronic address: xforns@clinic.cat.
Wyles D, Poordad F, Wang S, et al. SURVEYOR-II, Part 3: Efficacy and safety of glecaprevir/pibrentasvir (ABT-493/ABT-530) in patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or cirrhosis. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston, MA, November 11-15, 2016.
no abstract available
Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment.
Gane E, Lawitz E, Pugatch D, Papatheodoridis G, Bräu N, Brown A, Pol S, Leroy V, Persico M, Moreno C, Colombo M, Yoshida EM, Nelson DR, Collins C, Lei Y, Kosloski M, Mensa FJ
N Engl J Med. 2017;377(15):1448.
BACKGROUND: Chronic hepatitis C virus (HCV) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease. Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end-stage renal disease than those who have chronic kidney disease without HCV infection. Patients with both HCV infection and advanced chronic kidney disease have limited treatment options.
METHODS: We conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease (with or without cirrhosis) with severe renal impairment, dependence on dialysis, or both. Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon, ribavirin, sofosbuvir, or a combination of these medications. The primary end point was a sustained virologic response 12 weeks after the end of treatment.
RESULTS: Among the 104 patients enrolled in the trial, 52% had genotype 1 infection, 16% had genotype 2 infection, 11% had genotype 3 infection, 19% had genotype 4 infection, and 2% had genotype 5 or 6 infection. The sustained virologic response rate was 98% (102 of 104 patients; 95% confidence interval, 95 to 100). No patients had virologic failure during treatment, and no patients had a virologic relapse after the end of treatment. Adverse events that were reported in at least 10% of the patients were pruritus, fatigue, and nausea. Serious adverse events were reported in 24% of the patients. Four patients discontinued the trial treatment prematurely because of adverse events; three of these patients had a sustained virologic response.
CONCLUSIONS: Treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection. (Funded by AbbVie; ClinicalTrials.gov number, NCT02651194 .).
From the Liver Unit, Auckland City Hospital, Auckland, New Zealand (E.G.); the Texas Liver Institute, University of Texas Health, San Antonio (E.L.); AbbVie, North Chicago, IL (D.P., C.C., Y.L., M.K., F.J.M.); the Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens (G.P.); the James J. Peters Veterans Affairs Medical Center, Bronx, and Icahn School of Medicine at Mount Sinai, New York - both in New York (N.B.); Imperial College Healthcare, London (A.B.); Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris (S.P.), and Centre Hospitalier Universitaire de Grenoble, Grenoble (V.L.) - both in France; the Internal Medicine and Hepatology Unit, University of Salerno, Salerno (M.P.), Humanitas Clinical and Research Center, Rozzano (M.C.), and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Universitàdi Milano, Milan (M.C.) - all in Italy; Cliniques