2015, Number 1
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Ann Hepatol 2015; 14 (1)
Effects on anemia of drug adjustment in patients with chronic hepatitis C during telaprevir-combined therapy
Tamori A, Kioka K, Sakaguchi H, Enomoto M, Hai H, Kawamura E, Hagihara A, Fujii H, Uchida-Kobayashi S, Iwai S, Morikawa H, Murakami Y, Kawasaki Y, Tsuruta D, Kawada N
Language: English
References: 35
Page: 28-35
PDF size: 210.73 Kb.
ABSTRACT
Aim. Anemia is the most common adverse event in patients with chronic hepatitis C virus (HCV) treated
with telaprevir (TVR) combined triple therapy. We examined the effects of drug dose adjustment on anemia
and a sustained viral response (SVR) during combination therapy.
Material and methods. This study enrolled
62 patients treated with TVR (2,250 mg) for 12 weeks plus pegylated interferon-alpha-2b and ribavirin
for 24 weeks. The patients were assigned randomly to the TVR-standard or -reduced groups before treatment.
At the occurrence of anemia (hemoglobin ‹ 12 g/dL), the TVR-reduced group received 1500 mg TVR
plus the standard dose of ribavirin, whereas the TVR-standard group received the standard TVR dose
(2,250 mg) and a reduced dose of ribavirin (200 mg lower than prescribed originally). The safety and SVR at
24 weeks were compared between the TVR-standard (n = 28) and TVR-reduced (n = 25) groups.
Results. No
differences in the proportion of patients who became HCV RNA-negative were detected between the TVRstandard
and -reduced groups (72 and 72% at week 4, 79 and 84% at the end of treatment, and 76 and 80%
at SVR24, respectively). Two groups had comparable numbers of adverse events, which led to the discontinuation
of TVR in 14 patients of TVR-standard group and in 14 of TVR-reduced group. A lower incidence
of renal impairment was observed in the TVR-reduced group (6%) than the TVR-standard group (11%, not
statistically significant).
Conclusions. TVR dose adjustment could prevent anemia progression without
weakening the anti-viral effect during triple therapy in HCV-patients.
REFERENCES
Pearlman BL. Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care. Lancet Infect Dis 2012; 12: 717-28.
Imai Y, Tamura S, Tanaka H, Hiramatsu N, Kiso S, Doi Y, Inada M et al. Reduced risk of hepatocellular carcinoma after interferon therapy in aged patients with chronic hepatitis C is limited to sustained viological responders. J Viral Hepat 2010; 17: 185-91.
Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, Yasui Y, et al. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010; 52: 518-27.
McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, Dienstag J, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 2002; 123: 1061-9.
Coppola N, Pisaturo M, Tonziello G, Sagnelli C, Sagnelli E, Angelillo IF. Efficacy of pegylated interferon α-2a and α-2b in patients with genotype 1 chronic hepatitis C: a metaanalysis. BMC Infect Dis 2012; 12: 357.
Tamori A, Kioka K, Kurai O, Sakaguchi H, Enomoto M, Fujii H, Kobayashi S, et al. Favorable factors for re-treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus. Hepatol Res 2011; 41: 1169-77.
Hai H, Tamori A, Enomoto M, Morikawa H, Uchida-Kobayashi S, Fujii H, Hagihara A, et al. Relationship between inosine triphosphate genotype and outcome of extended therapy in hepatitis C virus patients with a late viral response to pegylated-interferon and ribavirin. J Gastroenterol Hepatol 2014; 29: 201-7.
Hézode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009; 360: 1839-50.
McHutchison JG, Manns MP, Muir AJ, Terrault NA, Jacobson IM, Afdhal NH, Heathcote EJ, et al. Telaprevir for previously treated chronic HCV infection. N Engl J Med 2010; 362: 1292-303.
Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, et al. ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364: 2405-16.
Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364: 2417-28.
Buti M, Agarwal K, Horsmans Y, Sievert W, Janczewska E, Zeuzem S, Nyberg L, et al. Telaprevir Twice Daily is Noninferior to Telaprevir Every 8 hrs for Patients with Chronic Hepatitis C. Gastroenterology 2014; 146: 744-53.
Furusyo N, Ogawa E, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, et al. Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C. J Hepatol 2013; 59: 205-12.
Colombo M, Fernández I, Abdurakhmanov D, Ferreira PA, Strasser SI, Urbanek P, Moreno C, et al. Safety and ontreatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C. Gut 2014; 63: 1150-8. 35 TVR dose reduction for anemia. , 2015; 14 (1): 28-35
Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 1433-44.
Editors of the Drafting Committee for Hepatitis Management Guidelines: The Japan Society of Hepatology Guidelines for the Management of Hepatitis C Virus Infection. Hepatol Res 2013; 43: 1-34.
Ogawa E, Furusyo N, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, et al. Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy. J Hepatol 2013; 59: 667-74.
Kumada H, Toyota J, Okanoue T, Chayama K, Tsubouchi H, Hayashi N. Telaprevir with peginterferon and ribavirin for treatment-naive patients chronically infected with HCV of genotype 1 in Japan. J Hepatol. 2012; 56: 78-84.
Hayashi N, Okanoue T, Tsubouchi H, Toyota J, Chayama K, Kumada H. Efficacy and safety of telaprevir, a new protease inhibitor, for difficult-to-treat patients with genotype 1 chronic hepatitis C. J Viral Hepat 2012; 19: e134-e142.
Kamar N, Chatelut E, Manolis E, Lafont T, Izopet J, Rostaing L. Ribavirin pharmacokinetics in renal and liver transplant patients: evidence that it depends on renal function. Am J Kidney Dis 2004; 43: 140-6.
Oze T, Hiramatsu N, Kurashige N, Tsuda N, Yakushijin T, Kanto T, Takehara T, et al. Early decline of hemoglobin correlates with progression of ribavirin-induced hemolytic anemia during interferon plus ribavirin combination therapy in patients with chronic hepatitis C. J Gastroenterol 2006; 41: 862-72.
Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009; 41: 1105-9.
Fellay J, Thompson AJ, Ge D, Gumbs CE, Urban TJ, Shianna KV, Little LD, et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature 2010; 464: 405-8.
Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, Lok AS, et al. Peginterferon alfa- 2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004; 126: 1015-23.
Suzuki F, Suzuki Y, Sezaki H, Akuta N, Seko Y, Kawamura Y, Hosaka T, et al. Exploratory study on telaprevir given every 8 h at 500 mg or 750 mg with peginterferon-alpha- 2b and ribavirin in hepatitis C patients. Hepatol Res 2013; 43: 691-701.
Kawakami Y, Suzuki F, Karino Y, Toyota J, Kumada H, Chayama K. Telaprevir is effective given every 12 hours at 750 mg with peginterferon-alfa-2b and ribavirin to Japanese patients with HCV-1b IL28B rs8099917 TT. Antivir Ther 2013 [in press].
Sezaki H, Suzuki F, Hosaka T, Akuta N, Fukushima T, Hara T, Kawamura Y, et al. Effectiveness and safety of reduced- dose telaprevir-based triple therapy in chronic hepatitis C patients. Hepatol Res 2013 [in press].
Reesink HW, Zeuzem S, Weegink CJ, Forestier N, van Vliet A, van de Wetering de Rooij J, McNair L, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX- 950: a phase Ib, placebo-controlled, randomized study. Gastroenterology 2006; 131: 997-1002.
McCurry J. Japan battles with obesity. Lancet 2007; 369: 451-52.
Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the Study of Obesity. New criteria for ‘obesity disease’ in Japan. Circ J 2002; 66: 987-92.
AASLD and IDSA. Recommendations for Testing, Managing, and Treating Hepatitis C 2014. Available at: http:// www.hcvguidelines.org
Zeuzem S, Berg T, Gane E, Ferenci P, Foster GR, Fried MW, Hezode C, et al. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology 2014; 146: 430-41.
Forns X, Lawitz E, Zeuzem S, Gane E, Bronowicki JP, Andreone P, Horban A, et al. Simeprevir with Peginterferon and Ribavirin Leads to High Rates of SVR in Patients with HCV Genotype 1 Who Relapsed After Previous Therapy: a Phase 3 Trial. Gastroenterology 2014; 146: 1669-79.
Izumi N, Hayashi N, Kumada H, Okanoue T, Tsubouchi H, Yatsuhashi H, Kato M, et al. Once-daily simeprevir with peginterferon and ribavirin for treatment-experienced HCV genotype 1-infected patients in Japan: the CONCERTO- 2 and CONCERTO-3 studies. J Gastroenterol 2014; 49: 941-53.
Halfon P, Locarnini S. Hepatitis C virus resistance to protease inhibitors. J Hepatol 2011; 55: 192-206.