Journal of Infectious Diseases Advance Access published June 26, 2014
1 Reply to "Telaprevir Activity in Treatment‐Naive Patients Infected Hepatitis C Virus
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Genotype 4: A Randomized Trial" by Benhamou et al. published on July 11, 2013
Roberta K. Sefcik, Kian Bichoupan, Valérie Martel-Laferrière, Joseph A. Odin,
Lawrence U. Liu, Ponni Perumalswami, Meena Bansal, Douglas T. Dieterich, Jawad
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Ahmad, Thomas D. Schiano, Andrea D. Branch
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Corresponding author: Roberta Sefcik –
[email protected] – Phone: (727) 7090180
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e‐mail:
[email protected].
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TO THE EDITOR-Benhamou et al. demonstrated that the tolerability and pharmacokinetics of telaprevir (T) in hepatitis C virus-infected (HCV) genotype 4 patients were similar to those found in HCV genotype 1 patients. In their study, HCV genotype 4 patients were randomized to: (a) T monotherapy for 15 days, (b) T, pegylatedinterferon α-2a and ribavirin (TPR) for 15 days, or (c) placebo, pegylated-interferon α-2a and ribavirin (PR) for 15 days. Following the initial 2 weeks, a standard treatment of PR was given for 46-48 weeks. The findings from this study support the investigation of TPR for 12 weeks and PR for an additional 36 weeks in HCV genotype 4 patients (1). With Institutional Review Board approval, we performed a chart review of HCV genotype 4 patients receiving TPR at Mount Sinai Hospital from April, 2011 until October 2012. The aim was to determine the rate of sustained virologic response-week 24 (SVR24), which was defined as undetectable HCV RNA 24 weeks after the end-of-treatment. Patients who were chronically infected with HCV genotype 4, and received at least one dose of T were included. The demographics of our patients are described in Table 1. Patients were treated with the TPR treatment algorithm approved for genotype 1
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HCV patients (TPR for 12 weeks then PR for an additional 12 (response-guided therapy) or 36 weeks) with the following exceptions (2). Patient 1 began TPR, and after two
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weeks it was discovered that he was given 200 mg RBV BID instead of 600 mg BID. He mistakenly discontinued telaprevir after 8 weeks, and PR treatment was discontinued due to virologic breakthrough (detectable HCV RNA after HCV RNA falls below the limit-
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of-detection on-treatment) that occurred after 41 weeks of treatment. Patient 3 began TPR, and decided to stop treatment after 40 weeks of treatment, and achieved a SVR24. Patient 5 initiated TPR, and after 11 weeks discontinued T due to adverse events. Patient 6 received nitazoxanide and PR treatment and his viral load after 4 weeks decreased to
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5,414 IU/mL, and he discontinued nitazoxanide at this time due to adverse events. T was added after 22 weeks for 12 weeks. After 31 weeks of treatment, his HCV RNA level
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fell below the limit of quantification, but he relapsed six weeks after the end-oftreatment. Patient 7 began TPR but discontinued treatment after 2 weeks due to adverse events (hepatic encephalopathy (HE), ascites, thrombocytopenia, and neutropenia). He
3 continued to decompensate, and was discharged to hospice 13 weeks after the end-oftreatment where he died.
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Our patients experienced similar adverse events to patients observed by
Benhamou and colleagues (1). The most common adverse events experienced by our patients included but were not limited to: flu-like symptoms, rash,
fatigue/weakness/shortness of breath, anemia, low neutrophil count, low platelets, low
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white blood cell count, anorectal symptoms, nausea/vomiting/diarrhea,
abdominal/stomach pain, pruritus, and constipation. Two patients experienced a liver
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decompensation (patient 5: HE; patient 7: HE, ascites, thrombocytopenia requiring platelet transfusion, and neutropenia). One patient required epoeitin, and 2 required
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epoeitin and a blood transfusion. Less common adverse events included but were not limited to: difficulty controlling diabetes that resolved after T discontinuation,
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conjunctivitis, hypothyroidism, vision changes, and depression and moodiness. Overall, 4 patients had visits to the ED. Reasons for emergency care included, but were not limited to: hepatic encephalopathy (572.2), urinary tract infection (599.0), anemia (285.9), abdominal pain (789.0), headache (784.0), back pain (724) and severe interferon reaction (995.29). Patient 1 developed hepatocellular carcinoma (HCC) within a year after
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treatment ended, and patient 7 had a history of HCC.
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We observed a 50% SVR24 rate. All of the patients that did not obtain a SVR24
were cirrhotic and did not follow the TPR treatment algorithm approved for HCV genotype 1 patients. One patient has not reached 24 weeks after the end-of-treatment. The SVR24 rate obtained in our study reflects the same SVR24 rate that Benhamou et al. found in patients treated with TPR for 15 days and then PR for 46 weeks. It is important
4 to note that our patients differed from those found in the study by Benhamou and colleagues, as we included an HIV co-infected patient, cirrhotic patients, and older
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patients (median age of 56 years (Range: 43-68 years) vs. 41 years (Range: 28-52 years). Our results reinforce the findings by Benhamou et al., and support additional research of
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TPR in HCV genotype 4 patients (1).
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Table 1. Patient demographics, baseline characteristics, and treatment response. Baseline
Age, Patient
Previously Gender
Race
year
Treatment
HIV
Cirrhosis Log HCV
treated
Outcome
Duration
RNA
Virologic
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Caucasian
Yes
43
M
Caucasian
No
3
51
F
Unknown
No
4
63
M
Caucasian
Yes
5
68
M
Caucasian
No
6
53
M
Caucasian
Yes
No
Yes
No
5.38
5.00
41 weeks
Breakthrough 24 weeks
SVR24
No
No
6.33
40 weeks
SVR24
No
No
6.27
48 weeks
SVR24
No
Yes
4.04
48 weeks
SVR5
No
Yes
5.47
41 weeks
Relapse
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2
No
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1
Treatment M
Caucasian
Yes
Yes
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60
Yes
4.78
2 weeks
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References 1.
Benhamou Y, Moussalli J, Ratziu V, Lebray P, De Backer K, De Meyer S, et al.
Telaprevir activity in treatment-naive patients infected hepatitis C virus genotype 4: a randomized trial. J Infect Dis 2013;208:1000-7. Epub 2013/06/27.
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2.
INCIVEK (telaprevir) Film Coated Tablets, for oral use. Available at
http://pi.vrtx.com/files/uspi_telaprevir.pdf (accessed 1, November 2013).
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6 Footnotes
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Roberta K. Sefcik, Kian Bichoupan, Valérie Martel-Laferrière, Joseph A. Odin, Lawrence U. Liu, Ponni Perumalswami, Meena Bansal, Douglas T. Dieterich, Jawad Ahmad, Thomas D. Schiano, Andrea D. Branch
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RS and MB have no financial disclosures. KB is a consultant for companies that include Gilead Sciences and Janssen Pharmaceuticals. ADB is a consultant for companies that include Gilead Sciences and Janssen Pharmaceuticals. DTD serves as a paid lecturer, consultant and is a member on scientific advisory boards of companies, which either develop or assess medicines used for the treatment of viral hepatitis. These companies include Gilead Sciences, Boehringer Ingelheim, Novartis, Vertex Pharmaceuticals, Achillion, Tibotex, Idenix, Merck, Kadmon, Bayer Healthcare, Genentech and HoffmanLa Roch, Inc. and Bristol-Myers Squibb. TDS is a paid lecturer, consultant and a participant in the DSMB of companies that include Bristol-Myers Squibb/sanofi-aventis partnership, Novartis, Pfizer Inc., and Salix Pharmaceuticals, Inc. Data from this article has not been previously presented.
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Declaration of funding interests: This study was funded in full by the National Institutes of Health DA031095 and DK090317 to ADB. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Valerie Martel-Laferriere: 2011 AMMI Canada/Pfizer Post Residency Fellowship, 2012 Grant of the CHUM Foundation.
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Corresponding author: Roberta Sefcik –
[email protected] – Phone: (727) 709-0180