Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomisedstudy

Author(s): Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, et al.

Abstract

Background: Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.

Methods: We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790.

Findings: 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12.

Interpretation: Combined simeprevir and sofosbuvir was efficacious and well tolerated.

Funding: Janssen.

Similar Articles

Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome

Author(s): Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, et al.

Global burden of disease (GBD) for hepatitis C

Author(s): Global Burden Of Hepatitis C Working Group

The hepatitis C virus life cycle as a target for new antiviral therapies

Author(s): Pawlotsky JM, Chevaliez S, McHutchison JG

Global distribution and prevalence of hepatitis C virus genotypes

Author(s): Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, et al.

HCV genotypes among 1013 Saudi nationals: a multicenter study

Author(s): Al Traif I, Al Balwi MA, Abdulkarim I, Handoo FA, Alqhamdi HS, et al.

Genetic epidemiology of hepatitis C virus throughout egypt

Author(s): Ray SC, Arthur RR, Carella A, Bukh J, Thomas DL

Telaprevir activity in treatment-naive patients infected hepatitis C virus genotype 4: a randomized trial

Author(s): Benhamou Y, Moussalli J, Ratziu V, Lebray P, De Backer K, et al.

Socioeconomic status in HCV infected patients - risk and prognosis

Author(s): Omland LH, Osler M, Jepsen P, Krarup H, Weis N, et al.

Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4

Author(s): Hasan F, Asker H, Al-Khaldi J, Siddique I, Al-Ajmi M, et al.

Response to pegylated interferon alfa-2a and ribavirin in chronic hepatitis C genotype 4

Author(s): El Makhzangy H, Esmat G, Said M, Elraziky M, Shouman S, et al.

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4

Author(s): Martín-Carbonero L, Puoti M, García-Samaniego J, De Luca A, Losada E, et al.

Sofosbuvir for previously untreated chronic hepatitis C infection

Author(s): Lawitz E, Mangia A Wyles D, Rodriguez-Torres M, Hassanein T, et al.

Efficacy and safety of sofosbuvir-based triple therapy in hepatitis C genotype 4 infection

Author(s): Wehmeyer MH, Jordan S, Lüth S, Hartl J, Stoehr A, et al.

Daclatasvir plus peginterferonalfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study

Author(s): Hézode C, Hirschfield GM, Ghesquiere W, Sievert W, Rodriguez-Torres M, et al.

Daclatasvir and asunaprevir plus peginterferonalfa and ribavirin in HCV genotype 1 or 4 non-responders

Author(s): Jensen D, Sherman KE, Hézode C, Pol S, Zeuzem S, et al.

Hepatitis C virus treatment in the real world: optimising treatment and access to therapies

Author(s): Zoulim F, Liang TJ, Gerbes AL Aghemo A4, Deuffic-Burban S5, et al.

Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4

Author(s): Doss W, Shiha G, Hassany M, Soliman R, Fouad R, et al.

Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection

Author(s): Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, et al.

Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection

Author(s): Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, et al.