Effectiveness of Simeprevir Plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients With HCV Genotype 1 Infection.
OBJECTIVE
The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America.


METHODS
We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET--a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most patients had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as the level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment--a 2-week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias.


RESULTS
The overall SVR rate was 84% (675 of 802 patients, 95% confidence interval, 81%-87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively.


CONCLUSIONS
In a large prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811.
Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: msulkowski@jhmi.edu.
Mark S
MS
Sulkowski
Mayo Clinic-Arizona, Phoenix, Arizona.
Hugo E
HE
Vargas
Saint Louis University School of Medicine, St. Louis, Missouri.
Adrian M
AM
Di Bisceglie
University of California, San Diego, California.
Alexander
A
Kuo
University of Pennsylvania, Philadelphia, Pennsylvania.
K Rajender
KR
Reddy
Yale University School of Medicine, New Haven, Connecticut.
Joseph K
JK
Lim
University of Florida School of Medicine, Gainesville, Florida.
Giuseppe
G
Morelli
University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Jama M
JM
Darling
Toronto Western Hospital Liver Center, Toronto, Canada.
Jordan J
JJ
Feld
Columbia University, New York, New York.
Robert S
RS
Brown
Liver Wellness Center, Little Rock, Arkansas.
Lynn M
LM
Frazier
University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Thomas G
TG
Stewart
University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Michael W
MW
Fried
University of Florida School of Medicine, Gainesville, Florida.
David R
DR
Nelson
Mount Sinai Beth Israel, New York, New York.
Ira M
IM
Jacobson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069616:Simeprevir / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D000998:Antiviral Agents; D015415:Biomarkers; D012367:RNA, Viral; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir
Chronic Hepatitis; Direct-Acting Agent; NS3/4A Protease Inhibitor; NS5B