PMID- 25363449
OWN - NLM
STAT- MEDLINE
DCOM- 20151123
LR  - 20150312
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 22
IP  - 4
DP  - 2015 Apr
TI  - Simeprevir with peginterferon/ribavirin for treatment of chronic hepatitis C 
      virus genotype 1 infection: pooled safety analysis from Phase IIb and III 
      studies.
PG  - 366-75
LID - 10.1111/jvh.12346 [doi]
AB  - This pooled analysis of five Phase IIb and III studies evaluated the safety and 
      tolerability of simeprevir, a once daily, oral hepatitis C virus (HCV) NS3/4A 
      protease inhibitor. Data were summarised for patients who received simeprevir 150 
      mg once daily (n = 924) or placebo (n = 540) plus pegylated 
      interferon-alpha/ribavirin for 12 weeks. During the first 12 weeks of treatment, few 
      patients discontinued simeprevir or placebo due to adverse events (AEs) (both 
      2.2%). Pruritus (23.8% vs 17.4%), rash (any; 22.9% vs 16.7%) and photosensitivity 
      (3.2% vs 0.6%) [Correction added on 16 January 2015, after first online 
      publication: In the above sentence, the values in 'Photosensitivity' were 
      previously incorrect and have now been changed to 3.2% vs 0.6%.] were more 
      prevalent in the simeprevir vs the placebo groups. Most AEs were grade 1/2 (72.4% 
      for simeprevir vs 71.3% for placebo). All grade 3/4 AEs occurred in <5.0% of 
      patients, except neutropenia (9.8% vs 7.6%). Overall incidence of neutropenia was 
      similar (17.3% vs 15.7%). Incidence of anaemia was 13.2% for simeprevir vs 10.9% 
      for placebo, and incidence of increased bilirubin was 8.4% vs 2.8%. Bilirubin 
      increases were mild-to-moderate and transient without concurrent transaminase 
      increases or association with hepatic injury. Safety and tolerability did not 
      vary with METAVIR score, although increased bilirubin and anaemia were more 
      frequent in simeprevir-treated patients with METAVIR F4 (increased bilirubin, 
      13.0% vs 3.3%; anaemia, 19.0% vs 14.8%). Serious AEs were infrequent (2.1% for 
      simeprevir vs 3.0% for placebo). No deaths were reported during the first 12 
      weeks of treatment. Patient-reported fatigue and other outcomes were comparable 
      for both groups, but were of shorter duration for simeprevir due to the use of 
      response-guided therapy. Simeprevir is well tolerated in HCV genotype 1-infected 
      patients.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Manns, M P
AU  - Manns MP
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Medizinische 
      Hochschule Hannover, Hannover, Germany.
FAU - Fried, M W
AU  - Fried MW
FAU - Zeuzem, S
AU  - Zeuzem S
FAU - Jacobson, I M
AU  - Jacobson IM
FAU - Forns, X
AU  - Forns X
FAU - Poordad, F
AU  - Poordad F
FAU - Peeters, M
AU  - Peeters M
FAU - Fu, M
AU  - Fu M
FAU - Lenz, O
AU  - Lenz O
FAU - Ouwerkerk-Mahadevan, S
AU  - Ouwerkerk-Mahadevan S
FAU - Jessner, W
AU  - Jessner W
FAU - Scott, J A
AU  - Scott JA
FAU - Kalmeijer, R
AU  - Kalmeijer R
FAU - De La Rosa, G
AU  - De La Rosa G
FAU - Sinha, R
AU  - Sinha R
FAU - Beumont-Mauviel, M
AU  - Beumont-Mauviel M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141103
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon-alpha)
RN  - 49717AWG6K (Ribavirin)
RN  - 9WS5RD66HZ (Simeprevir)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Anemia/chemically induced/epidemiology
MH  - Antiviral Agents/administration & dosage/*adverse effects
MH  - Bilirubin/blood
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Controlled Clinical Trials as Topic
MH  - Drug Therapy, Combination/adverse effects/methods
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/pathology
MH  - Exanthema/chemically induced/epidemiology
MH  - Genotype
MH  - Hepacivirus/classification/genetics
MH  - Hepatitis C, Chronic/*drug therapy/virology
MH  - Humans
MH  - Interferon-alpha/administration & dosage/*adverse effects
MH  - Neutropenia/chemically induced/epidemiology
MH  - Prevalence
MH  - Pruritus/chemically induced/epidemiology
MH  - Ribavirin/administration & dosage/*adverse effects
MH  - Simeprevir/administration & dosage/*adverse effects
OTO - NOTNLM
OT  - hepatitis C virus
OT  - protease inhibitor
OT  - safety
OT  - simeprevir
EDAT- 2014/11/05 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/11/04 06:00
PHST- 2014/05/16 00:00 [received]
PHST- 2014/09/03 00:00 [accepted]
PHST- 2014/11/04 06:00 [entrez]
PHST- 2014/11/05 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1111/jvh.12346 [doi]
PST - ppublish
SO  - J Viral Hepat. 2015 Apr;22(4):366-75. doi: 10.1111/jvh.12346. Epub 2014 Nov 3.