title: Simeprevir plus sofosbuvir for eight or 12 weeks in treatment-naïve and treatment-experienced hepatitis C virus genotype 4 patients with or without cirrhosis.
abstract: The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.
authors: Faculty of Medicine, Cairo University, Cairo, Egypt.
authors: M
authors: M
authors: El Raziky
authors: Janssen Research & Development, Beerse, Belgium.
authors: M
authors: M
authors: Gamil
authors: Faculty of Medicine, Cairo University, Cairo, Egypt.
authors: M K
authors: MK
authors: Ashour
authors: National Liver Institute, Menoufiya, Egypt.
authors: E A
authors: EA
authors: Sameea
authors: National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
authors: W
authors: W
authors: Doss
authors: Faculty of Medicine, Cairo University, Cairo, Egypt.
authors: Y
authors: Y
authors: Hamada
authors: Janssen Research & Development, Beerse, Belgium.
authors: G
authors: G
authors: Van Dooren
authors: Janssen Research & Development, Titusville, NJ, USA.
authors: R
authors: R
authors: DeMasi
authors: Janssen-Cilag Farmacêutica, Barcarena, Portugal.
authors: S
authors: S
authors: Keim
authors: Janssen Pharmaceuticals, Paris, France.
authors: I
authors: I
authors: Lonjon-Domanec
authors: National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
authors: R
authors: R
authors: Hammad
authors: National Liver Institute, Menoufiya, Egypt.
authors: M S
authors: MS
authors: Hashim
authors: National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
authors: M
authors: M
authors: Hassany
authors: National Liver Institute, Menoufiya, Egypt.
authors: I
authors: I
authors: Waked
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D000069616:Simeprevir / Q000008:administration & dosage* / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000069616:Simeprevir; D000069474:Sofosbuvir
keywords: Egypt; genotype 4; hepatitis C; simeprevir; sustained virologic response