TY - JOUR
T1 - 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
T2 - The COSMOS randomised study
AU - Lawitz, Eric
AU - Sulkowski, Mark S.
AU - Ghalib, Reem
AU - Rodriguez-Torres, Maribel
AU - Younossi, Zobair M.
AU - Corregidor, Ana
AU - Dejesus, Edwin
AU - Pearlman, Brian
AU - Rabinovitz, Mordechai
AU - Gitlin, Norman
AU - Lim, Joseph K.
AU - Pockros, Paul J.
AU - Scott, John D.
AU - Fevery, Bart
AU - Lambrecht, Tom
AU - Ouwerkerk-Mahadevan, Sivi
AU - Callewaert, Katleen
AU - Symonds, William T.
AU - Picchio, Gaston
AU - Lindsay, Karen L.
AU - Beumont, Maria
AU - Jacobson, Ira M.
N1 - Funding Information:
EL has received research support from AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Presidio, Roche, Santaris Pharmaceuticals, and Vertex Pharmaceuticals; has acted as part of the speaker's bureau for Gilead, Janssen, Kadmon, Merck, and Vertex Pharmaceuticals; and has been a board or advisory panel member for AbbVie, Achillion Pharmaceuticals, BioCryst, Biotica, Enanta, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Santaris Pharmaceuticals, Theravance, and Vertex Pharmaceuticals. MSS is a member of the Janssen Pharmaceuticals Scientific Advisory Board; has acted as a consultant or advisory board member for AbbVie Inc, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb, Gilead Sciences Inc, Idenix Pharmaceuticals Inc, Merck & Co Inc, and Tobira Therapeutics Inc; has participated on the data safety monitoring board for Gilead Sciences Inc and the study steering committee for Pfizer Inc; and has been an investigator for AbbVie Inc, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb, Gilead Sciences Inc, Merck & Co Inc, and Vertex Pharmaceuticals. MR-T has acted as a consultant or advisor for Akros, Bristol-Myers Squibb, Genentech, Hoffman-La Roche, Inhibitex, Janssen, Merck Sharp & Dohme, Pharmasset, Santaris, and Vertex, and has received research/grant support from Abbott, Akros, Anadys, Beckman Coulter, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead, GlaxoSmithKline, Hoffman-La Roche, Human Genome Sciences, Idenix, Idera, Inhibitex, Janssen, Merck Sharp & Dohme, Mochida, Novartis, Pfizer, Pharmasset, Santaris Pharma, Scynexis, Siemens Healthcare Diagnostics, Vertex, and Zymogenetics. ZMY has acted as a consultant or advisor for Gilead Sciences Inc, Janssen, Bristol-Myers Squibb, Merck, Achillion Pharmaceuticals, Salix Pharmaceuticals, Conatus, and Synageva. BP has received research grants from Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, and Merck and acted as a speaker for Gilead Sciences Inc, Janssen, Kadmon, Merck, and Vertex. MR has acted as an advisor for Janssen. NG has received research grants from, and acted as a speaker for, Bristol-Myers Squibb, Gilead, Janssen, Merck, Roche/Genentech, and Vertex. JKL has received research grants from Abbott, Achillion, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead, Janssen, and Vertex; and served as an advisor/consultant to Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, and Merck. PJP has received research grants from Janssen, Vertex, Gilead, Bristol-Myers Squibb, Boehringer Ingelheim, Roche/Genentech, Intercept, Novartis, Beckman Coulter, Mochida and Pfizer; served as an advisor/consultant to Janssen, Vertex, Gilead, Bristol-Myers Squibb, Roche/Genentech, Intercept, Merck, Novartis, Beckman Coulter, and Mochida; and acted as a speaker for Vertex, Merck, and Bristol-Myers Squibb. JDS has received research or grant support from Gilead, Janssen, Merck, Roche/Genentech, and Vertex; served as an advisor/consultant to Gilead and Tacere Therapeutics; acted as a speaker for Janssen, Merck, and Roche/Genentech; and has a patent pending for antiviral resistance testing. BF, SO-M, KC, GP, RK, and MB are employees of Janssen Research and Development. KLL is a former employee of Janssen Research and Development. WTS is an employee of Gilead Sciences Inc. IMJ has received research or grant support from AbbVie, Achillion, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Novartis, Roche, Merck, Janssen, and Vertex; has acted as a consultant or adviser for AbbVie, Achillion, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Idenix, Novartis, Roche, Schering, Merck, Janssen, and Vertex; and has been on the speaker's bureau for Bristol-Myers Squibb, Gilead, Janssen, Roche, and Vertex. The other authors declare that they have no competing interests.
PY - 2014/11/15
Y1 - 2014/11/15
N2 - 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.
AB - 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.
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U2 - 10.1016/S0140-6736(14)61036-9
DO - 10.1016/S0140-6736(14)61036-9
M3 - Article
C2 - 25078309
AN - SCOPUS:84911409020
SN - 0140-6736
VL - 384
SP - 1756
EP - 1765
JO - The Lancet
JF - The Lancet
IS - 9956
ER -