2015, Number 1
<< Back Next >>
Ann Hepatol 2015; 14 (1)
Boceprevir and telaprevir for chronic genotype 1 hepatitis C virus infection. A systematic review and meta-analysis
Manzano-Robleda MC, Ornelas-Arroyo V, Barrientos-Gutiérrez T, Méndez-Sánchez N, Uribe M, Chávez-Tapia NC
Language: English
References: 50
Page: 46-57
PDF size: 136.77 Kb.
ABSTRACT
Background. Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic
in some countries because of the lack of availability. Aim. Assess benefits and harms of boceprevir (BOC)
and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit.
Material and methods. Search from 2009-2013 in PubMed, EMBASE, and “gray literature” of published
and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC
or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison
protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines
were applied. Comparisons between PI + PR
vs. PR were performed. Main outcomes were expressed
as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed.
Results. 33 studies
(10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression,
previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE
were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95%
CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis,
statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels.
In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed
superior response rates. Specific predictors will determine the best candidates for treatments that will offer
real-life therapeutic alternatives.
REFERENCES
Guidelines for the screening, care and treatment of persons with hepatitis infection. World Health Organization 2014. Available at: www.who.int/about/licensing/ copyright_form/en/index.html.
Jayasekera CR, Barry M, Roberts LR, Nguyen MH. Treating hepatitis C in lower-income countries. N Engl J Med 2014; 370: 1869-71.
AASLD and IDSA Launch Web-Based Recommendations for Testing, Managing, and Treating HCV. AASLD 2014.
Yokoyama S, Takahashi S, Kawakami Y, Hayes CN, Kohno H, Kohno H, Tsuji K, et al. Effect of vitamin D supplementation on pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b: a randomized controlled trial. J Viral Hepat 2014; 21: 348-56.
Pearlman BL, Ehleben C. Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferManzano- Robleda MC, et al. , 2015; 14 (1): 46-57 56 on/ribavirin obviates a protease inhibitor. Hepatology 2014; 59: 71-7.
Park C, Jiang S, Lawson KA. Efficacy and safety of telaprevir and boceprevir in patients with hepatitis C genotype 1: a meta-analysis. J Clin Pharm Ther 2014; 39: 14-24.
Coppola N, Pisaturo M, Sagnelli C, Sagnelli E, Angelillo IF. Peg-Interferon Plus Ribavirin with or without Boceprevir or Telaprevir for HCV Genotype 1: A Meta-Analysis on the Role of Response Predictors. PLoS One 2014; 9: e94542.
Chou R, Hartung D, Rahman B, Wasson N, Cottrell EB, Fu R. Comparative effectiveness of antiviral treatment for hepatitis C virus infection in adults: a systematic review. Ann Intern Med 2013; 158: 114-23.
Lawitz EJ, Membreno FE. Response-Guided Therapy in Patients with Genotype 1 HCV: Current Status and Future Prospects. J Gastroenterol Hepatol 2014; 29 (8): 1574-81 doi: 10.1111/jgh.12632.
Jensen DM, Morgan TR, Marcellin P, Pockros PJ, Reddy KR, Hadziyannis SJ, Ferenci P, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy. Hepatology 2006; 43: 954-60.
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
G.A.W. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Otawa Hospital Reaserch Institute. Available at: http:// www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Thorlund K. User manual for trial sequential analysis (TSA). Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark; 2011, p. 1-115.
Hezode 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.
McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360: 1827-38.
Sulkowski M. Telaprevir in Combination with Peginterferon Alfa- 2a/Ribavirin in HCV/HIV Co-infected Patients: SVR24 Final Study Results. Hepatology 2012; 56: 1144A.
Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1207-17.
Poordad F, McCone J, Jr., Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195-206.
Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364: 2405-16.
Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT, Fried MW, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 2011; 365: 1014-24.
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.
Sulkowski M, Pol S, Mallolas J, Fainboim H, Cooper C, Slim J, Rivero A, et al. Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. Lancet Infect Dis 2013; 13: 597-605.
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.
Flamm SL, Lawitz E, Jacobson I, Bourliere M, Hezode C, Vierling JM, Bacon BR, et al. Boceprevir with peginterferon alfa-2a-ribavirin is effective for previously treated chronic hepatitis C genotype 1 infection. Clin Gastroenterol Hepatol 2013; 11: 81-87, e84; quiz e85.
Sulkowski MS, Sherman KE, Dieterich DT, Bsharat M, Mahnke L, Rockstroh JK, Gharakhanian S, et al. Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann Intern Med 2013; 159: 86-96.
Coilly A, Roche B, Dumortier J, Leroy V, Botta-Fridlund D, Radenne S, Pageaux GP, et al. Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: a multicenter experience. J Hepatol 2014; 60: 78-86.
Hezode C, Fontaine H, Dorival C, Larrey D, Zoulim F, Canva V, de Ledinghen V, et al. Triple therapy in treatmentexperienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) - NCT01514890. J Hepatol 2013; 59: 434-41.
Akiyama MJ, Piotrowski JI, Roytman MM, Chan SM, Hong LK, Huddleston L, Trujillo R, et al. New triple therapy for chronic hepatitis C: real life clinical experience in a community setting. Hawaii J Med Public Health 2013; 72: 6-13.
Backus LI, Belperio PS, Shahoumian TA, Cheung R, Mole LA. Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large U.S. cohort. Aliment Pharmacol Ther 2014; 39: 93-103.
Singh G. The Real Life Experience With the Development and Management of Anemia in the Era of Protease Inhibitors for Chronic Hepatitis C Infection. Gastroenterology 2013; 144: S-1136.
Sulkowski M. Anemia during treatment with peginterferon alfa-2b/ ribavirin with or without boceprevir is associated with higher svr rates: analysis of previously untreated and previous-treatment-failure patients. J Hepatol 2011; 54: 594.
Karino Y. Analysis of the optimal TVR dose per weight judging from anemia during PEG-IFN/RBV/TVR combination therapy. J Hepatol 2013; 58: S338.
Lawitz E. Timing and magnitude of ribavirin dose reduction (RBV DR) do not impact sustained virologic response (SVR) rates with boceprevir (BOC) + peginterferon alfa-2b/ribavirin (P/RBV) in the Anemia Management Study in chronic HCV genotype 1 patients. Hepatology 2012; 56: 1144A.
Purohit T. Is Week 1 (W1) and Week 2 (W2) Monitoring Helpful in Patients Treated for Chronic Hepatitis C With Pegylated Interferon, Ribavirin and a Protease Inhibitor. Gastroenterology 2013; 144: S983-S984.
Asahina Y. Serum Interleukin-6 levels during treatment correlate with resistance to Telaprevir based triple therapy in chronic hepatitis C. J Hepatol 2013; 58: S321.
Ogawa E. Impact of the viral kinetics of chronic hepatitis C patients treated with telaprevir in combination with Pegylated Interferon A2b and Ribavirin. J Hepatol 2013; 58: S-632.
Susser S, Vermehren J, Forestier N, Welker MW, Grigorian N, Fuller C, Perner D, et al. Analysis of long-term persistence of resistance mutations within the hepatitis C virus NS3 protease after treatment with telaprevir or boceprevir. J Clin Virol 2011; 52: 321-7.
Hoffmann L, Ramos JA, Souza EV, Araujo Ramos AL, Villela- Nogueira CA, Urmenyi TP, Tanuri A, et al. Dynamics of resistance mutations to NS3 protease inhibitors in a cohort of Brazilian patients chronically infected with hepatitis C virus (genotype 1) treated with pegylated interferon and ribavirin: a prospective longitudinal study. Virol J 2013; 10: 57.
Thomas XV. Long-Term Follow-Up Of Chronic Hepatitis C Infected Patients Treated With Telaprevir: Evaluation Of Persistence Of Resistant Variants By Ultra-Deep Sequencing. J Hepatol 2011; 54: S490-S491.
Pinson P. Dynamics Of Hcv Quasispecies During Telaprevir Treatment Dissected Using Ultra-Deep Pyrosequencing: Treatment Failure In 100% Of Genotype 1a Patients. J Hepatol 2012; 56: S614.
Volpe JM. Cross-sectional Assessment of Telaprevir and Boceprevir resistance-associated mutations of 500 clinical samples submitted for HCV NS3/4A protease inhibitor drug resistance testing in the US. Hepatology 2012; 54: 1144A.
Velazquez C. Timing And Characteristics Of Drug Resistance Mutations (Drms) In Chronic Hepatitis C Patients During And After Treatment With Protease Inhibitor Therapy At A Single Centre. J Hepatol 2013; 58: S632.
Messina E. Amino Acid Change In The Positions Associated With Protease Inhibitors Resistance Is Less Frequent In Genotype 3 Than In Genotype 1 Hcv Natural Strain. J Hepatol 2013; 58: S632.
Galmozzi. Clinical implications of baseline population sequencing of the NS3 protease in HCV-1 partial or null-responders to Peg-interferon/ribavirin. Dig Liver Dis 2013; 45: S54.
Cento V. HCV Kinetics And Quasispecies Evolution Within The First Hours Of Telaprevir-Based Triple Therapy In Previously Treated HCV-Patients. J Hepatol 2013; 58: S632.
Cento V. Correlation Of Early Detection Of Hcv Ns3-Resistance And Virological Failure In Patients Treated With Triple Therapy Including Telaprevir Or Boceprevir. J Hepatol 2013; 58: S632.
Rau M, Baur K, Geier A. Host genetic variants in the pathogenesis of hepatitis C. Viruses 2012; 4: 3281-302.
Halfon P, Locarnini S. Hepatitis C virus resistance to protease inhibitors. J Hepatol 2011; 55: 192-206.
Leggewie M, Sreenu VB, Abdelrahman T, Leitch EC, Wilkie GS, Klymenko T, Muir D, et al. Natural NS3 resistance polymorphisms occur frequently prior to treatment in HIV-positive patients with acute hepatitis C. AIDS 2013; 27: 2485-8.