2013 Telaprevir Versus Boceprevir in Chronic Hepatitis C- A Meta-Analysis of Data From Phase II and...

7/24/2019 2013 Telaprevir Versus Boceprevir in Chronic Hepatitis C- A Meta-Analysis of Data From Phase II and III Trials

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Telaprevir Versus Boceprevir in Chronic Hepatitis C: AMeta-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; andMichael Malloy, PharmD

Massachusetts College of Pharmacy & Health Sciences, Worcester, Massachusetts

ABSTRACT

Background: Telaprevir and boceprevir are pro-

tease 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 (Peg-

IFNRBV). 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 48-

week sustained viral responses (SVR) and drug-related

adverse events (AEs) between telaprevir and bocepre-

vir triple-therapy regimens in the treatment of chronic

HCV infection.

Methods:MEDLINE, EMBASE, and Cochrane da-

tabases were searched for articles published from Jan-

uary 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 inter-

feron ribavirin (Peg-IFNRBV). 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 meta-

analysis (N 4144 treatment-naive and treatment-

experienced patients). With telaprevir, the ORs (95%

CI) for SVR at 24 weeks in treatment-naive and treat-

ment-experienced patients were 3.31 (2.274.82; P

0.0001) and 4.21 (1.839.72; P 0.001), respectively.

Telaprevir triple therapy did not result in more drug-

related discontinuations but did cause additional rash,

pruritis, and anemia. With boceprevir, the ORs (95%

CI) were improved in both treatment-naive and treat-

ment 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.

Conclusions:Based on the findings from this meta-

analysis, telaprevir or boceprevir combined with Peg-

IFN 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, hepati-

tis C genotype 1, protease inhibitors, telaprevir.

INTRODUCTIONInfection with chronic hepatitis C virus (HCV) in-

creases the risk for life-threatening hepatocellular car-

cinoma and cirrhosis in

170 million patients world-wide.1 Of the six hepatitis C genotypes, genotype 1 is

the most common and difficult to treat.2 Combination

treatment with pegylated interferon ribavirin (Peg-

IFNRBV) is a preferred approach for achieving sus-

tained viral response (SVR; defined as an undetectable

concentration of HCV RNA at 24 weeks after the com-

pletion 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 inter-

feron offers once-weekly dosing (instead of TIW),making interferon ribavirin combinations easier to

manage while improving rates of SVR.69 Newer ap-

proaches to improving treatment response include

adding a novel protease inhibitor to an existing regi-

men 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.

Clinical Therapeutics/Volume 35, Number 2, 2013

190 Volume 35 Number 2
http://dx.doi.org/10.1016/j.clinthera.2012.12.017http://dx.doi.org/10.1016/j.clinthera.2012.12.017


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Administration has approved triple-therapy combina-

tions of a specific protease inhibitor (telaprevir or bo-

ceprevir) 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 non-structural 3/4A serine protease.13,14 Telaprevir and bo-

ceprevir increase the likelihood of early SVR, but there

are no data on important long-term outcomes, includ-

ing effects on the risk for hepatocellular carcinoma and

hepatic-related mortality, with either agent used ad-

junctively with Peg-IFN RBV.13,10,1517 Because

these 2 protease inhibitors have similar mechanisms of

action, clinicians may consider these drugs interchange-

able; however, tolerability, foodpreferences, and pillbur-

den may influence individual treatment decisions.

For the purposes of the present meta-analysis, theinvestigators chose to review and systematically pool

available data from prospective Phase II and III ran-

domized 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 Peg-

IFN 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 datawere pooled for a final summary response to consider

the views of an institution responsible for ordering or

stocking medications on-formulary.

METHODSLiterature Search

A search of the MEDLINE, EMBASE, and Co-

chrane 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 (Jan-

uary 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-

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. Dis-

agreements on eligibility were resolved by evaluating

objective data from each study and discussion.

Inclusion and Exclusion CriteriaRCTs 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 telaprevir-

based 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 PatientsA studys eligibility and quality were determined us-

ing a standardized, nonblinded evaluation process and

electronic form. All trials satisfying the inclusion crite-

ria were independently evaluated by 2 authors (M. Si-

tole and M. Silva) to extract data on study quality and

end points, including SVR at 24 and 48 weeks (if avail-

able). 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-re-

gression of final outcomes according to groups char-

acteristics. Information collected for meta-regression

included patients age, sex, race, HCV RNA concen-

tration, baseline alanine aminotransferase (ALT) con-

centration, and hepatic fibrosis staging (graded as no

or minimal fibrosis, portal fibrosis, or bridging fibro-

sis), together with cirrhosis status. Data were com-

pared prior to analysis to identify discrepancies, which

were resolved by review and discussion.

End PointsA standardized definition of SVR (undetectable

HCV RNA 6 months after the last dose of treatment)

was used. SVR at 24weekswas 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 pop-

ulations were of interest. Combined SVRs, which in-

cluded data from both treatment-nave and treatment-

M. Sitole et al.

February 2013 191


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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 bo-

ceprevir) 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 tel-

aprevir (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 indi-

rectly compared these 2 active treatments to each other

in a simple pairwise comparison. The likelihood of

achieving SVR (odds ratio [OR] [95% CI]) was calcu-

lated and assessed using the random-effects model and

Comprehensive Meta-Analysis version 2 (BioStat In-

ternational, Inc, Englewood, New Jersey).19 Heteroge-

neity was evaluated using the Cochran Q score and the

I2 statistic, and funnel plots were reviewed to estimate

the extent of publication bias.1922 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.

RESULTSThe search yielded 586 studies, 22 of which were RCTs

of telaprevir or boceprevir (Figure). There were 586

records identified using applied limits. Studies without

control groups or failing to report outcomes data were

omitted, leaving 8 for inclusion in the analysis (telapre-

vir, 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 Ishows the baseline characteristics of the pa-

tients who received telaprevir or boceprevir in the trials

(mean or median age, 49 years [range, 1870 years]).

Treatment-naive telaprevir and boceprevir patients rep-

resented 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, 5684

and 6.36.67 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).

TelaprevirFive studies in 2124 patients including treatment-

naive and treatment-experienced groups were included

in the telaprevir analysis. In the treatment-naive pa-

tients, SVR at 24 weeks was greater in the telaprevir

586 Records identified throughdatabase searching

564 Records excluded

11 RCTs excluded : no comparativetreatment groups

1 RCTs excluded : patient characteristics2 RCTs excluded : no control group

22 RCTs identified and screened

11 RCTs assessed for eligibility

8 Studies included in finalquantitative meta-analysis

Figure. Results of search strategy used to identify the randomized controlled trials (RCTs) included in this

meta-analysis of telaprevir versus bocepavir.

Clinical Therapeutics



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Table I. Baseline characteristics of the patients in the randomized controlled trials included in this meta-anal

NS3 Protease Inhibitor/Source/Treatment History

No. ofPatients

Age

MaleSex, %

Baseline

ALT,IU/L Genotype

HCV RNA

log(10),IU/mL

Fibrosis Status

Cirrhosis,n or %Range

Mean/Median

None or

Minimal,n or %

Portal,%

Bridging,%

Telaprevir

Treatment naive

(n 1120)

McHutchison

(PROVE-1)3233 1865 49.3 62.2 1a, 1b

Hezode et al

(PROVE-2)4163 1865 45.5 61.5 55.5 1a, 1b 6.45 38.5% 51 10.5 0.01% 1250 m

then

q8h

Jacobson et al

(ADVANCE)23724 1869 49 58.5 84 1a, 1b 6.67 23.4% 35 26.4 15.4% 1125 m

dosin

750 m

Treatment experienced

(n 1004)

McHutchison et al(PROVE-3)1

342 1865 51 68.7 79 1a, 1b 6.6 24 29 22.4 25 750 mg

Zeuzem et al

(REALIZE)16662 2170 50.7 69.3 83.3 1a, 1b, 1c 6.3 37 43 14.4 5.8% 750 mg

Boceprevir

Treatment naive

(n 1617)

Kwo et al (SPRINT-

1)10520 1860 47.3 58.6 NR 1a, 1b 6.55 NR NR NR 7.6% 800 mg

Poordad et al

(SPRINT-2) 171,097 1860 49.3 59.7 NR 1a, 1b 800 mg

Treatment experienced

(n 403)

Bacon et al

(RESPOND-2)2403 1860 52.7 67.3 69 1a, 1b 12 800 mg

ALT alanine aminotransferase; NS3nonstructural 3; NRnotreported; PROVEMembersof theProtease Inhibitionfor Viral Evaluation; ADVANCEA N

Hepatitis C Patients with telaprevir; REALIZE Retreatment of Patients with Telaprevir-based Regimen to Optimize Outcomes; RESPOND Retreatme

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 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.

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Peg-IFNRBV treated group compared with the con-

trol group (OR 3.31; 95% CI, 2.274.82; P

0.0001) (Table II). In the treatment-experienced pa-

tients, 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 Peg-

IFN 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 con-

trol groups (OR 8.46; 95% CI, 5.7212.50; P

0.0001). Combined 24 and 48 week responses were

similar among treatment-naive and treatment-experi-

enced patients (OR 3.59; 95% CI, 2.535.11; P

0.0001) and (OR 4.1; 95% CI, 1.749.65; 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, 0.150.37; P 0.0001) but not in treatment-

experienced 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.

Table II. Sustained viral response (SVR), early response, and relapse data from the randomized controlled trialsincluded in this meta-analysis of telaprevir versus bocepavir.

Trials MH OR 95% CI z Score P

Responders

Q Score I2 NNT*Treated Control

24-Wk SVR

Telaprevir

Treatment naive 2 3.31 2.274.82 6.22 0.0001 372/521 189/436 1 0 2

Treatment experienced 2 4.27 2.736.7 6.34 0.0001 116/196 54/196 1 0 3

Combined 4 3.59 2.535.11 7.14 0.0001 488/717 243/632 3.45 12.9 3

Boceprevir

Treatment naive 2 3.55 2.574.89 7.72 0.0001 319/470 176/466 1 0 3

Treatment experienced 1 7.34 3.9213.8 6.23 0.0001 107/161 17/80 NA NA 2

Combined 3 4.52 2.777.38 6.03 0.0001 426/631 193/546 1.84 0 3

48-Wk SVR

Telaprevir

Treatment naive 2 1.98 1.422.76 4.04 0.0001 143/230 194/436 0.32 0 6

Treatment experienced 2 8.46 5.7212.5 10.7 0.0001 406/643 38/247 0.58 0 2

Combined 4 4.09 1.749.65 3.22 0.001 549/873 232/683 2.53 0 3Boceprevir

Treatment naive 1 2.95 2.233.9 7.56 0.0001 358/469 244/467 0.45 0 4

Early response

Telaprevir (4 wk)

Treatment naive 2 22 15.231.9 16.3 0.0001 384/539 42/436 0.62 0 2

Treatment experienced 2 48.2 6.83340 3.89 0.0001 401/647 13/264 1.41 0 2

Combined 4 26.1 15.344.5 12 0.0001 785/1186 55/700 3.86 0 2

Boceprevir (8 wk)

Treatment naive 2 3.39 0.85113.48 1.73 0.083 250/307 73/164 1 0 3


Combined 3 5.03 1.7614.4 3.02 0.003 334/468 80/244 2.28 12.2 3

Relapse

TelaprevirTreatment naive 2 0.24 0.160.37 6.46 0.0001 30/365 109/396 0.03 0 5

Treatment experienced 2 0.607 0.0438.52 0.371 0.711 92/584 51/210 1.58 0 7

Boceprevir

Treatment naive 2 0.263 0.150.462 4.66 0.0001 20/333 49/266 0.58 0 8


MH Mantel-Haenszel; NNT number needed to treat; OR odds ratio; SVR sustained viral response.

*Rounded up or down to the nearest patient.




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Treatment with telaprevir-based triple therapy did not

result in more discontinuations due to adverse drug reac-

tions compared with controls (OR 1.43; 95% CI,

0.424.92; P 0.57). Telaprevir was associated with an

increase in treatment-associated AEs compared with pla-

cebo (Table III). It was calculated that treating 100 (naive

or experienced) HCV patients with telaprevir-based tri-

ple therapy would result in 18 additional reports of rash,

18 of pruritis, and 15 of anemia.

BoceprevirThree studies in 2020 patients (including treatment-

naive and treatment-experienced groups) were included

in the boceprevir analysis. In treatment-naive patients,

24-week SVR was improved in the group that received

boceprevircomparedwithcontrols (OR3.55; 95% CI,

2.664.56; 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 treat-

ment-naive and previously treated patients continued to

demonstrate improved 24-week SVR in the boceprevir-

treated 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 com-

pared with thecontrol group (OR1.98; 95% CI,1.42

2.76); this finding was also true in the treatment-experi-

enced subgroup (OR 8.46; 95% CI, 5.7212.5).

Boceprevir was associated with increased preva-

lences of anemia and dysgeusia (Table III). It was cal-

culated 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 BoceprevirAn indirect treatment comparison between telapre-

vir and boceprevir favored telaprevir for inducing 24-

week SVR in treatment-naive patients (OR 1.78;

95% CI, 1.392.28;P 0.0001); however, the rates

of 48-week SVR in treatment-naive patients were sim-

ilar between telaprevir and boceprevir (OR 0.82;

95% CI, 0.61.11; P 0.2). Telaprevir and boceprevir

were also similar regarding discontinuation from

ADRs (OR 1.23; 95% CI, 0.951.6; P 0.11).

DISCUSSIONTelaprevir and boceprevir are protease inhibitors now

added to therapy for patients with chronic HCV geno-

type 1 infection who are either treatment naive or have

a history of relapse or recurrence following a previous

course of treatment with Peg-IFNRBV. 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

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

AE OR 95% CI P NNH

Telaprevir-related AEs

Any AE leading to D/C 1.43 0.424.92 0.57 96

Any rash 2.40 1.673.43 0.0001 6

Pruritis 2.36 1.773.14 0.0001 6

Anemia 2.33 1.713.18 0.0001 7

Diarrhea 1.62 1.162.25 0.005 12

Nausea 1.67 1.322.10 0.0001 10

Boceprevir-related AEs

Any AE leading to D/C 1.48 0.683.24 0.33 53

Anemia 2.5 1.963.2 0.0001 5

Chills 1.2 0.911.59 0.2 26

Diarrhea 1.09 0.841.41 0.51 46Dysgeusia 3.88 2.875.26 0.0001 4

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

M. Sitole et al.

February 2013 195


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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 im-

proved 24- and 48-week SVR in treatment-naive pa-

tients and treatment-experienced patients. The risk for

relapse was reduced in patients who were new to ther-

apy but not among those who had undergone a previ-ous course of treatment.

We also found that 4-week response rates supported

the practice of response-guided therapy, which mini-

mizes 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 in-

formation 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 be-

tween telaprevir and boceprevir was provided because:

(1) direct, randomized trials comparing the 2 agents have

not been performed; (2) the treatment-naive and treat-

ment-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 effi-

cacy 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 treat-

ment according to their preferences, and are able to

tolerate the drug-related AEs occurring during ther-

apy. 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

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 telapre-

vir, 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 coin-

fected 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-expe-

rienced 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 Jap-

anese patients who were treatment naive. After careful

review and evaluation of AEs during the course of

treatment, it was found that Japanese patients experi-

enced rates of drug-related AEs that were 3- to 5-fold

greater compared with US and European popula-tions.22 Therefore, Japanese patients should be as-

sessed separately to account for differences in the treat-

ment response owing to possible genetic differences in

bioavailability or drug metabolism.

CONCLUSIONSTriple 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 bo-ceprevir 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 hepatocel-

lular 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-compar-

ison trials of telaprevir versus boceprevir regimens




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would provide physicians with better insight into treat-

ment response and treatment-related AEs.

ACKNOWLEDGMENTSDrs. Sitole and Silva were involved in all parts of this

meta-analysis (study design, data collection, analysis,manuscript writing and revisions). Dr. Spooner contrib-

uted to study design, data analysis, manuscript writing.

Dr. Comee contributed to data collection and analysis.

Dr. Malloy contributed to data analysis and revision.

CONFLICTS OF INTERESTThe authors have indicated that they have no conflicts

of interest with regard to the content of this article.

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

College of Pharmacy & Health SciencesWorcester/Manchester, 19 Foster

Street, Worcester, MA 01608. E-mail: [email protected]

M. Sitole et al.

February 2013 197
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm255390.htmhttp://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm255390.htmhttp://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htmhttp://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htmmailto:[email protected]:[email protected]://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htmhttp://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htmhttp://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm255390.htmhttp://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm255390.htm


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