Clinical Therapeutics/Volume 35, Number 2, 2013

Telaprevir Versus Boceprevir in Chronic Hepatitis C: A

Meta-Analysis of Data From Phase II and III Trials
Mugdha Sitole, BSc, PharmD; Matthew Silva, PharmD, BCPS;
Linda Spooner, PharmD, BCPS; Morgan K. Comee, PharmD; and
Michael Malloy, PharmD
Massachusetts College of Pharmacy & Health Sciences, Worcester, Massachusetts
ABSTRACT
Background: Telaprevir and boceprevir are protease inhibitors now added to therapy for patients with
chronic hepatitis C virus (HCV) genotype 1 infection
who either are treatment naive or have a history of
relapse or recurrence following a previous course of
treatment with pegylated interferon ribavirin (PegIFN RBV). Because these agents are fairly new to the
market, providers may have limited experience with
them in the management of chronic HCV.
Objective: This meta-analysis compared 24- and 48week sustained viral responses (SVR) and drug-related
adverse events (AEs) between telaprevir and boceprevir triple-therapy regimens in the treatment of chronic
HCV infection.
Methods: MEDLINE, EMBASE, and Cochrane databases were searched for articles published from January 1995 to October 2012 on randomized controlled
trials that reported SVR at 24 weeks in patients with
HCV receiving triple-therapy regimens that included
telaprevir or boceprevir or placebo pegylated interferon ribavirin (Peg-IFN RBV). Pooled odds ratios
(ORs) were calculated and used to compare SVR at 24
and 48 weeks. Secondary end points included common
drug-related AEs and treatment discontinuations.
Results: Eight studies were included in this metaanalysis (N 4144 treatment-naive and treatmentexperienced patients). With telaprevir, the ORs (95%
CI) for SVR at 24 weeks in treatment-naive and treatment-experienced patients were 3.31 (2.27 4.82; P
0.0001) and 4.21 (1.839.72; P 0.001), respectively.
Telaprevir triple therapy did not result in more drugrelated discontinuations but did cause additional rash,
pruritis, and anemia. With boceprevir, the ORs (95%
CI) were improved in both treatment-naive and treatment experienced patients (3.55 [2.66-4.56; P
0.0001] and 7.34 [3.9213.9; P 0.0001]), but with
more treatment-related anemia and dysgeusia.

190

Conclusions: Based on the findings from this metaanalysis, telaprevir or boceprevir combined with PegIFN RBV had favorable short-term data on SVR
while resulting in more drug-related AEs. Extended
follow-up is required to determine whether these
agents offer a reduction in the risk for chronic hepatitis
C genotype 1related mortality and/or hospitalization.
(Clin Ther. 2013;35:190197) 2013 Elsevier HS
Journals, Inc. All rights reserved.
Key words: boceprevir, chronic hepatitis C, hepatitis C genotype 1, protease inhibitors, telaprevir.

INTRODUCTION
Infection with chronic hepatitis C virus (HCV) increases the risk for life-threatening hepatocellular carcinoma and cirrhosis in 170 million patients worldwide.1 Of the six hepatitis C genotypes, genotype 1 is
the most common and difficult to treat.2 Combination
treatment with pegylated interferon ribavirin (PegIFN RBV) is a preferred approach for achieving sustained viral response (SVR; defined as an undetectable
concentration of HCV RNA at 24 weeks after the completion of treatment) in patients with uncomplicated
infection with chronic HCV genotype 1.3 SVR rates in
these patients range from 40% to 50%, with rates as
low as 19% among black patients.4,5 Pegylated interferon offers once-weekly dosing (instead of TIW),
making interferon ribavirin combinations easier to
manage while improving rates of SVR.6 9 Newer approaches to improving treatment response include
adding a novel protease inhibitor to an existing regimen of Peg-IFN RBV.13,10 The US Food and Drug
Accepted for publication December 28, 2012.
http://dx.doi.org/10.1016/j.clinthera.2012.12.017
0149-2918/$ - see front matter
2013 Elsevier HS Journals, Inc. All rights reserved.

Volume 35 Number 2

M. Sitole et al.
Administration has approved triple-therapy combinations of a specific protease inhibitor (telaprevir or boceprevir) pegylated interferon (alfa 2a or alfa 2b)
ribavirin, administered for up to 48 weeks in patients
with HCV genotype 1 infection.11,12 Telaprevir and
boceprevir are reversible, selective, orally bioavailable
chronic HCV protease inhibitors specific to the nonstructural 3/4A serine protease.13,14 Telaprevir and boceprevir increase the likelihood of early SVR, but there
are no data on important long-term outcomes, including effects on the risk for hepatocellular carcinoma and
hepatic-related mortality, with either agent used adjunctively with Peg-IFN RBV.13,10,1517 Because
these 2 protease inhibitors have similar mechanisms of
action, clinicians may consider these drugs interchangeable; however, tolerability, food preferences, and pill burden may influence individual treatment decisions.
For the purposes of the present meta-analysis, the
investigators chose to review and systematically pool
available data from prospective Phase II and III randomized controlled trials (RCTs) in patients with
chronic HCV genotype 1 infection to determine
whether there were differences in SVR with telaprevir
or boceprevir added to an existing regimen of PegIFN RBV. The objectives were to review the rates of
SVR at 24 and 48 weeks, together with commonly
reported treatment-associated adverse events (AEs).
Patients new to treatment were considered separately
from those who were treatment experienced, and data
were pooled for a final summary response to consider
the views of an institution responsible for ordering or
stocking medications on-formulary.

METHODS
Literature Search
A search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify and select
original Phase II and III RCTs of triple therapy with
telaprevir or boceprevir or placebo Peg-IFN RBV
in treatment-naive and treatment-experienced patients
with chronic HCV genotype 1 infection. Search terms
included telaprevir, boceprevir, and chronic hepatitis
C. We imposed search limits by publication date (January 1995 to October 2012) to reflect current practice
and included published peer-reviewed, full-length,
English-language studies reporting an SVR of 24
weeks and drug-related AEs. References of retrieved
articles were reviewed to identify additional articles,
and investigators were contacted with requests to iden-

February 2013

tify unpublished data meeting the criteria for inclusion

in the present meta-analysis. Two reviewers (M. Sitole
and M. Silva) reviewed abstracts and selected full-text
articles of retrieved records to evaluate eligibility. Disagreements on eligibility were resolved by evaluating
objective data from each study and discussion.

Inclusion and Exclusion Criteria

RCTs that compared SVRs at 24 weeks between
1 group receiving triple therapy with telaprevir or
boceprevir Peg-IFN RBV and a group receiving
placebo Peg-IFN RBV (placebo control group)
were included in the analysis. Trials with telaprevirbased treatment arms included 12- and 8-hour dosing
regimens, whereas boceprevir trials used 8-hour treatment
regimens only. Reports describing subgroup analysis and
other duplicate post hoc reinterpretations were omitted.

Baseline Characteristics of Patients

A studys eligibility and quality were determined using a standardized, nonblinded evaluation process and
electronic form. All trials satisfying the inclusion criteria were independently evaluated by 2 authors (M. Sitole and M. Silva) to extract data on study quality and
end points, including SVR at 24 and 48 weeks (if available). Quality scores were evaluated using the standard
Oxford (Jadad) quality scoring system.18 Drug-related
AEs and discontinuations were included for review.
Patients characteristics were extracted for meta-regression of final outcomes according to groups characteristics. Information collected for meta-regression
included patients age, sex, race, HCV RNA concentration, baseline alanine aminotransferase (ALT) concentration, and hepatic fibrosis staging (graded as no
or minimal fibrosis, portal fibrosis, or bridging fibrosis), together with cirrhosis status. Data were compared prior to analysis to identify discrepancies, which
were resolved by review and discussion.

End Points
A standardized definition of SVR (undetectable
HCV RNA 6 months after the last dose of treatment)
was used. SVR at 24 weeks was selected as an end point
of interest, and SVR at 48 weeks, when available and
reported, was also included. This review included
data from treatment-naive and treatment-experienced
patients because the response rates in both patient populations were of interest. Combined SVRs, which included data from both treatment-nave and treatment-

191

Clinical Therapeutics

586 Records identified through

database searching

564 Records excluded

22 RCTs identified and screened

11 RCTs excluded : no comparative

treatment groups

11 RCTs assessed for eligibility

1 RCTs excluded : patient characteristics

2 RCTs excluded : no control group

8 Studies included in final

quantitative meta-analysis

Figure. Results of search strategy used to identify the randomized controlled trials (RCTs) included in this
meta-analysis of telaprevir versus bocepavir.

experienced patients, were compared at 24 and 48

weeks of treatment to represent the viewpoint of a
pharmacy or a managed-care organization that offered
telaprevir or boceprevir to its members. The rate of
rapid (at 4 weeks with telaprevir or 8 weeks with boceprevir) viral response to treatment and the rate of
relapse were also assessed. Other end points explored
were AEs resulting in discontinuation of the study drug
and AEs commonly reported with the use of either telaprevir (anemia, diarrhea, nausea, pruritis, and rash) or
boceprevir (anemia, chills, diarrhea, and dysgeusia).
The present meta-analysis compared the effects of
telaprevir or boceprevir to those of placebo and indirectly compared these 2 active treatments to each other
in a simple pairwise comparison. The likelihood of
achieving SVR (odds ratio [OR] [95% CI]) was calculated and assessed using the random-effects model and
Comprehensive Meta-Analysis version 2 (BioStat International, Inc, Englewood, New Jersey).19 Heterogeneity was evaluated using the Cochran Q score and the
I2 statistic, and funnel plots were reviewed to estimate
the extent of publication bias.19 22 Absolute risk was
derived from the reported rate of events and used to
calculate a number needed to treat (NNT) for SVR and
number needed to harm (NNH) for AEs.

RESULTS
The search yielded 586 studies, 22 of which were RCTs
of telaprevir or boceprevir (Figure). There were 586

192

records identified using applied limits. Studies without

control groups or failing to report outcomes data were
omitted, leaving 8 for inclusion in the analysis (telaprevir, 5; boceprevir, 3).1,3,4,10,16,17,23 A telaprevir study
in Japanese patients was excluded from the analysis
due to a varying AE profile specific to the Japanese
population.24 A review of references did not identify
additional records.
Table I shows the baseline characteristics of the patients who received telaprevir or boceprevir in the trials
(mean or median age, 49 years [range, 18 70 years]).
Treatment-naive telaprevir and boceprevir patients represented 27% and 39% of patients, respectively, in the
present analysis. Treatment-experienced telaprevir and
boceprevir patients represent 24% and 10% of patients,
respectively. Approximately 63% of patients enrolled
were men with hepatitis C genotype 1a or 1b. Baseline
concentrations of ALT and HCV RNA (ranges, 56 84
and 6.3 6.67 log(10) IU/mL, respectively) were reported
in most of the studies. Fibrosis was reported differently
between trials, using either staging or assigned Metavir
scores. Studies included in the present meta-analysis had
a minimum Oxford score of 3 (range, 35).

Telaprevir
Five studies in 2124 patients including treatmentnaive and treatment-experienced groups were included
in the telaprevir analysis. In the treatment-naive patients, SVR at 24 weeks was greater in the telaprevir

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February 2013

Table I. Baseline characteristics of the patients in the randomized controlled trials included in this meta-analysis of telaprevir versus bocepavir.*
Age

NS3 Protease Inhibitor/

Source/Treatment History
Telaprevir
Treatment naive
(n 1120)
McHutchison
(PROVE-1)3
Hezode et al
(PROVE-2)4
Jacobson et al
(ADVANCE)23
Treatment experienced
(n 1004)
McHutchison et al
(PROVE-3)1
Zeuzem et al
(REALIZE)16
Boceprevir
Treatment naive
(n 1617)
Kwo et al (SPRINT1)10
Poordad et al
(SPRINT-2)17
Treatment experienced
(n 403)
Bacon et al
(RESPOND-2)2

HCV RNA None or

log(10), Minimal,
n or %
IU/mL

Range

Mean/
Median

Male
Sex, %

Baseline
ALT,
IU/L

233

1865

49.3

62.2

1a, 1b

163

1865

45.5

61.5

55.5

1a, 1b

724

1869

49

58.5

84

342

1865

51

68.7

662

2170

50.7

520

1860

47.3

No. of
Patients

Dosing

Fibrosis Status

Ribavirin Dosing

Oxford
Quality
Score

Assessor
Blinding

1250 mg on day 1,
then 750 mg
q8h
1125 mg loading
dosing, then
750 mg q8h

10001200 mg/d
for 24 or 48 wk

Unknown

10001200 mg/d
for 24 or 48 wk

Unknown

750 mg q8h

10001200 mg/d
for 48 wk
10001200 mg/d
for 48 wk

Unknown

Unknown

800 mg TID

8001400 mg/d

Unknown

800 mg TID

6001400 mg/d

Yes

800 mg TID

6001400 mg/d

Yes

Portal,
%

Bridging,
%

Cirrhosis,
n or %

PI

6.45

38.5%

51

10.5

0.01%

1a, 1b

6.67

23.4%

35

26.4

15.4%

79

1a, 1b

6.6

24

29

22.4

25

69.3

83.3

1a, 1b, 1c

6.3

37

43

14.4

5.8%

750 mg q8h

58.6

NR

1a, 1b

6.55

NR

NR

NR

7.6%

Genotype

1,097

1860

49.3

59.7

NR

1a, 1b

403

1860

52.7

67.3

69

1a, 1b

12

193

M. Sitole et al.

ALT alanine aminotransferase; NS3 nonstructural 3; NR not reported; PROVE Members of the Protease Inhibition for Viral Evaluation; ADVANCE A New Direction in HCV Care: A Study of Treatment-Naive
Hepatitis C Patients with telaprevir; REALIZE Retreatment of Patients with Telaprevir-based Regimen to Optimize Outcomes; RESPOND Retreatment with HCV Serine Protease Inhibitor Boceprevir and
PegIntron/Rebetol 2; SPRINT Serine Protease Inhibitor Therapy 2.
*All studies were double-blind (investigator and patient) with the exception of Kwo et al (SPRINT-1),10 which was open-label. Randomization and allocation concealment were unknown in all studies.

All patients received pegylated interferon alfa-2a 180 g/wk (telaprevir studies) or alfa-2b 1.5 g/kg (boceprevir studies).

Metavir score was used to report liver status at enrollment.

Clinical Therapeutics

Table II. Sustained viral response (SVR), early response, and relapse data from the randomized controlled trials
included in this meta-analysis of telaprevir versus bocepavir.
Responders
Trials
24-Wk SVR
Telaprevir
Treatment naive
Treatment experienced
Combined
Boceprevir
Treatment naive
Treatment experienced
Combined
48-Wk SVR
Telaprevir
Treatment naive
Treatment experienced
Combined
Boceprevir
Treatment naive
Early response
Telaprevir (4 wk)
Treatment naive
Treatment experienced
Combined
Boceprevir (8 wk)
Treatment naive
Treatment experienced
Combined
Relapse
Telaprevir
Treatment naive
Treatment experienced
Boceprevir
Treatment naive
Treatment experienced

MH

OR

95% CI

z Score

Treated

Control

Q Score

I2

NNT*

2
2
4

3.31
4.27
3.59

2.274.82
2.736.7
2.535.11

6.22
6.34
7.14

0.0001
0.0001
0.0001

372/521
116/196
488/717

189/436
54/196
243/632

1
1
3.45

0
0
12.9

2
3
3

2
1
3

3.55
7.34
4.52

2.574.89
3.9213.8
2.777.38

7.72
6.23
6.03

0.0001
0.0001
0.0001

319/470
107/161
426/631

176/466
17/80
193/546

1
NA
1.84

0
NA
0

3
2
3

2
2
4

1.98
8.46
4.09

1.422.76
5.7212.5
1.749.65

4.04
10.7
3.22

0.0001
0.0001
0.001

143/230
406/643
549/873

194/436
38/247
232/683

0.32
0.58
2.53

0
0
0

6
2
3

2.95

2.233.9

7.56

0.0001

358/469

244/467

0.45

2
2
4

22
48.2
26.1

15.231.9
6.83340
15.344.5

16.3
3.89
12

0.0001
0.0001
0.0001

384/539
401/647
785/1186

42/436
13/264
55/700

0.62
1.41
3.86

0
0
0

2
2
2

2
1
3

3.39
11.4
5.03

0.85113.48
4.9426.2
1.7614.4

1.73
5.71
3.02

0.083
0.0001
0.003

250/307
84/161
334/468

73/164
7/80
80/244

1
NA
2.28

0
NA
12.2

3
2
3

0.160.37
0.0438.52

6.46
0.371

0.0001
0.711

30/365
92/584

109/396
51/210

0.03
1.58

0
0

5
7

4.66
2.49

0.0001
0.013

20/333
8/25

49/266
14/121

0.58
NA

0
NA

8
5

2
2

0.24
0.607

2
1

0.263
3.6

0.150.462
1.319.86

MH Mantel-Haenszel; NNT number needed to treat; OR odds ratio; SVR sustained viral response.
*Rounded up or down to the nearest patient.

Peg-IFN RBV treated group compared with the control group (OR 3.31; 95% CI, 2.27 4.82; P
0.0001) (Table II). In the treatment-experienced patients, the SVR rates at 24 weeks were similar between
the active and control groups (OR 4.21; 95% CI,
1.839.72; P 0.001). In the treatment-naive patients,
SVR at 48 weeks was greater in the telaprevir PegIFN RBV treated group compared with the control
group (OR 1.98; 95% CI, 1.422.76; P 0.0001).
In the treatment-experienced patients, 48-week SVR
rates were similar between the triple-therapy and control groups (OR 8.46; 95% CI, 5.7212.50; P

194

0.0001). Combined 24 and 48 week responses were

similar among treatment-naive and treatment-experienced patients (OR 3.59; 95% CI, 2.535.11; P
0.0001) and (OR 4.1; 95% CI, 1.74 9.65; P
0.001). In treatment-naive patients, there was less
investigator-defined relapse among telaprevir-treated
patients compared with the control group (OR 0.24;
95% CI, 0.15 0.37; P 0.0001) but not in treatmentexperienced patients (OR 0.61; 95% CI, 0.05 8.13;
P 0.71). Rapid viral response to telaprevir at 4 weeks
was predictive of 24-week SVR in treatment-naive and
-experienced patients.

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M. Sitole et al.

Table III. Treatment-related adverse events (AEs) reported in the randomized controlled trials included in this
meta-analysis of telaprevir versus bocepavir.
AE

OR

95% CI

NNH

Telaprevir-related AEs
Any AE leading to D/C
Any rash
Pruritis
Anemia
Diarrhea
Nausea

1.43
2.40
2.36
2.33
1.62
1.67

0.424.92
1.673.43
1.773.14
1.713.18
1.162.25
1.322.10

0.57
0.0001
0.0001
0.0001
0.005
0.0001

96
6
6
7
12
10

Boceprevir-related AEs
Any AE leading to D/C
Anemia
Chills
Diarrhea
Dysgeusia

1.48
2.5
1.2
1.09
3.88

0.683.24
1.963.2
0.911.59
0.841.41
2.875.26

0.33
0.0001
0.2
0.51
0.0001

53
5
26
46
4

D/C discontinuation; NNH number needed to harm; OR odds ratio.

Treatment with telaprevir-based triple therapy did not

result in more discontinuations due to adverse drug reactions compared with controls (OR 1.43; 95% CI,
0.42 4.92; P 0.57). Telaprevir was associated with an
increase in treatment-associated AEs compared with placebo (Table III). It was calculated that treating 100 (naive
or experienced) HCV patients with telaprevir-based triple therapy would result in 18 additional reports of rash,
18 of pruritis, and 15 of anemia.

Boceprevir
Three studies in 2020 patients (including treatmentnaive and treatment-experienced groups) were included
in the boceprevir analysis. In treatment-naive patients,
24-week SVR was improved in the group that received
boceprevir compared with controls (OR 3.55; 95% CI,
2.66 4.56; P 0.0001); this finding was also true in the
treatment-experienced subgroup (OR 7.34; 95% CI,
3.9213.9; P 0.0001) (Table II). Combining treatment-naive and previously treated patients continued to
demonstrate improved 24-week SVR in the boceprevirtreated group (OR 4.52; 95% CI, 2.777.38; P
0.0001). In the treatment-naive subgroup, 48-week SVR
was improved in the group that received boceprevir compared with the control group (OR 1.98; 95% CI, 1.42
2.76); this finding was also true in the treatment-experienced subgroup (OR 8.46; 95% CI, 5.7212.5).

February 2013

Boceprevir was associated with increased prevalences of anemia and dysgeusia (Table III). It was calculated that treating 100 (naive or experienced) HCV
patients with boceprevir-based triple therapy would
result in 21 additional instances of anemia and 26 of
dysgeusia linked to treatment.

Telaprevir Versus Boceprevir

An indirect treatment comparison between telaprevir and boceprevir favored telaprevir for inducing 24week SVR in treatment-naive patients (OR 1.78;
95% CI, 1.39 2.28; P 0.0001); however, the rates
of 48-week SVR in treatment-naive patients were similar between telaprevir and boceprevir (OR 0.82;
95% CI, 0.6 1.11; P 0.2). Telaprevir and boceprevir
were also similar regarding discontinuation from
ADRs (OR 1.23; 95% CI, 0.951.6; P 0.11).

DISCUSSION
Telaprevir and boceprevir are protease inhibitors now
added to therapy for patients with chronic HCV genotype 1 infection who are either treatment naive or have
a history of relapse or recurrence following a previous
course of treatment with Peg-IFN RBV. These agents
are fairly new to the market, and providers may still
have limited experience with them in the management
of chronic HCV. The present meta-analysis found 8

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Clinical Therapeutics
studies covering Phase II and III trials, and each found
telaprevir or boceprevir to improve the likelihood of
SVR while resulting in predictable AEs. Telaprevir improved 24- and 48-week SVR in treatment-naive patients and treatment-experienced patients. The risk for
relapse was reduced in patients who were new to therapy but not among those who had undergone a previous course of treatment.
We also found that 4-week response rates supported
the practice of response-guided therapy, which minimizes treatment exposure and may reduce the overall
impact of resistance. Because Peg-IFN RBV therapy
has a high baseline for treatment-related AEs, producing
some type of treatment-related AE in nearly all patients
during therapy, we expected more discontinuations when
telaprevir was added to an existing regimen of Peg-IFN
RBV. Instead, telaprevir triple therapy did not result in
more treatment-related discontinuations due to ADRs
compared with placebo Peg-IFN RBV; however,
triple therapy did result in higher prevalences of anemia,
rash, and pruritis.
Boceprevir also improved 24- and 48-week SVR in
treatment-naive patients and treatment-experienced
patients, although the available data supplied less information regarding early responses to therapy and
discontinuations. Boceprevir was also associated with
increased prevalences of anemia and dysgeusia.
A simple indirect comparison of 24-week SVR between telaprevir and boceprevir was provided because:
(1) direct, randomized trials comparing the 2 agents have
not been performed; (2) the treatment-naive and treatment-experienced patient populations in these telaprevir
and boceprevir trials were similar; and (3) the control
groups were similar in these studies of telaprevir or
boceprevir.
We were unable to find published literature that did
not use 24- or 48-week SVR to demonstrate the efficacy of triple therapy. Although this finding could be
interpreted as publication bias, it may also suggest that
triple therapy with either agent is more effective when
patients are informed of the ADR profile, choose treatment according to their preferences, and are able to
tolerate the drug-related AEs occurring during therapy. Discussions between providers and patients about
expected ADRs during the course of therapy is crucial
because each drug has a unique AE profile, different
patient populations show highly variable rates of
ADRs, and patients will choose medications differently
according to their preferences. Additionally, there are

196

differences between telaprevir and boceprevir in terms

of food requirements and pill burden; these must be
reviewed with patients prior to treatment initiation to
ensure that patients will be able to adhere to therapy. For
example, some patients may prefer not to have to ingest
foods with at least 20 g of fat every 8 hours, as is required
with telaprevir, thus preferring the use of boceprevir.
Also, some patients may be overwhelmed by the idea of
taking 4 boceprevir capsules every 8 hours in addition to
their other medications, thus preferring the use of telaprevir, which is dosed as 2 tablets every 8 hours. All of these
factors should be considered when selecting treatment
regimens for individuals with HCV genotype 1 infection.
Studies in this analysis did not assess patients coinfected with HCV/HBV and/or HCV/HIV; therefore,
the authors could not evaluate treatment effects in this
group of patients. Moreover, direct-comparison trials
of telaprevir versus boceprevir triple therapy have not
been performed in treatment-naive or treatment-experienced patients, which limits an absolute comparison
of efficacy and tolerability in these populations with
HCV genotype 1 infection. A recent study excluded
from this analysis reflects the unique responses of Japanese patients who were treatment naive. After careful
review and evaluation of AEs during the course of
treatment, it was found that Japanese patients experienced rates of drug-related AEs that were 3- to 5-fold
greater compared with US and European populations.22 Therefore, Japanese patients should be assessed separately to account for differences in the treatment response owing to possible genetic differences in
bioavailability or drug metabolism.

CONCLUSIONS
Triple therapy consisting of telaprevir or boceprevir in
combination with Peg-IFN RBV for HCV genotype
1 infection resulted in more patients reaching SVR at
24 and 48 weeks but also in more drug-related AEs.
The short-term treatment response to telaprevir or boceprevir using disease-oriented end points was robust
in a mix of treatment-naive and -experienced patients;
however, little is known about whether telaprevir or
boceprevir reduces the longer-term risk for hepatocellular carcinoma. Telaprevir and boceprevir are new
pharmacologic entities; extended follow-up is needed
to determine the effects of treatment in HCV mortality
and/or disease-related hospitalization. Direct-comparison trials of telaprevir versus boceprevir regimens

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M. Sitole et al.
would provide physicians with better insight into treatment response and treatment-related AEs.
10.

ACKNOWLEDGMENTS
Drs. Sitole and Silva were involved in all parts of this
meta-analysis (study design, data collection, analysis,
manuscript writing and revisions). Dr. Spooner contributed to study design, data analysis, manuscript writing.
Dr. Comee contributed to data collection and analysis.
Dr. Malloy contributed to data analysis and revision.

11.

12.

CONFLICTS OF INTEREST
The authors have indicated that they have no conflicts
of interest with regard to the content of this article.
13.

REFERENCES
1. McHutchison JG, Manns MP, Muir AJ, et al. Telaprevir for
previously treated chronic HCV infection. N Engl J Med.
2010;362:12921303.
2. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for
previously treated chronic HCV genotype 1 infection. N Engl
J Med. 2011;364:12071217.
3. McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir
with peginterferon and ribavirin for chronic HCV genotype
1 infection. N Engl J Med. 2009;360:18271838.
4. Hezode C, Forestier N, Dusheiko G, et al. Telaprevir and
peginterferon with or without ribavirin for chronic HCV
infection. N Engl J Med. 2009;360:1839 1850.
5. Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b
and ribavirin for the treatment of chronic hepatitis C in
blacks and non-Hispanic whites. N Engl J Med. 2004;350:
22652271.
6. Glue P, Fang JW, Rouzier-Panis R, et al, for the Hepatitis C
Intervention Therapy Group. Pegylated interferon-alpha2b:
pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Clin Pharmacol Ther. 2000;68:556 567.
7. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon
alfa-2a plus ribavirin for chronic hepatitis C virus infection.
N Engl J Med. 2002;347:975982.
8. Chung RT, Andersen J, Volberding P, et al. Peginterferon
Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin
for chronic hepatitis C in HIV-coinfected persons. N Engl
J Med. 2004;351:451 459.
9. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al.
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C

14.
15.

16.
17.

18.

19.
20.
21.

22.
23.

24.

virus infection in HIV-infected patients. N Engl J Med.

2004;351:438 450.
Kwo PY, Lawitz EJ, McCone J, et al. Efficacy of boceprevir,
an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with
genotype 1 hepatitis C infection (SPRINT-1): an openlabel, randomised, multicentre phase 2 trial. Lancet. 2010;
376:705716.
US Food and Drug Administration. FDA approves Victrelis
for Hepatitis C. http://www.fda.gov/NewsEvents/Newsroom/
PressAnnouncements/ucm255390.htm. Accessed September 5, 2012.
US Food and Drug Administration. Approval of Incivek
(telaprevir), a direct acting antiviral drug (DAA) to treat
hepatitis C (HCV). http://www.fda.gov/ForConsumers/
ByAudience/ForPatientAdvocates/ucm256328.htm. Accessed April 27, 2012.
Victrelis (boceprevir) [prescribing information]. Whitehouse Station, NJ: Merck; 2012.
Incivek (telaprevir) [prescribing information]. Cambridge,
Mass: Vertex Pharmaceuticals Inc; 2012.
Sherman KE, Flamm SL, Afdhal NH, et al. Response-guided
telaprevir combination treatment for hepatitis C virus
infection. N Engl J Med. 2011;365:1014 1024.
Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:24172428.
Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for
untreated chronic HCV genotype 1 infection. N Engl J Med.
2011;364:11951206.
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality
of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:112.
DerSimonian R, Laird N. Meta-analysis in clinical trials.
Control Clin Trials. 1986;7:177188.
Ioannidis JP. Interpretation of tests of heterogeneity and bias
in meta-analysis. J Eval Clin Pract. 2008;14:951957.
Sutton AJ JD, Abrams KR, Sheldon TA, Song F. Publication
bias. In: Methods for Meta-Analysis in Medical Research. 1 ed.
Chichester, UK: John Wiley & Sons; 2000.
Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring
inconsistency in meta-analyses. BMJ. 2003;327:557560.
Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus
infection. N Engl J Med. 2011;364:24052416.
Kumada H, Toyota J, Okanoue T, et al. Telaprevir with
peginterferon and ribavirin for treatment-naive patients
chronically infected with HCV of genotype 1 in Japan.
J Hepatol. 2012;56:78 84.

Address correspondence to: Mugdha Sitole. BSc, PharmD, Massachusetts

College of Pharmacy & Health SciencesWorcester/Manchester, 19 Foster
Street, Worcester, MA 01608. E-mail: mugdha.sitole@mcphs.edu

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