Nuevos fármacos en el abordaje terapéutico de la hepatitis C

R. Jimenez Galan, Á. Albacete Ramirez, P. Monje Agudo, Y. Borrego Izquierdo, R. Morillo Verdugo

Resumen


Objetivos: Analizar la eficacia y seguridad de los nuevos agentesantivirales directos (AAD) que formaran parte del arsenal terapéuticopara el tratamiento de la hepatitis C.Método: Se realizó una búsqueda en la base de datos electrónicaPubMed, de artículos publicados Febrero de 2014 quecumplieran los siguientes criterios: ensayos clínicos (EC) en faseII o III y cuyos objetivos fueran evaluar la eficacia y seguridad denuevas generaciones de inhibidores de la proteasa (IP) frente alVHC, excluyendo con boceprevir y telaprevir.Resultados: Se incluyeron de 24 EC que incluyen asociacionesde AAD con ribavirina (RBV) y con o sin peginterferon (PegINF)y asociaciones de varios AAD. Los resultados de daclatasvircon PegINF y RBV no han sido muy satisfactorios. Por el contrario,sofosbuvir es activo en todos los genotipos virales y permiteser administrado en regímenes libres de PegINF. Alrededordel 90% de los pacientes naïve alcanzan respuesta viralsostenida (RVS) , y no llegan al 80% en pretratados. En cuantoa la segunda generación de IP NS3/4A, destacar a simeprevir,con respuestas próximas al 90% en pacientes naïve y cercanasal 80% en pretratados. Entre las combinaciones de AAD evaluadas,sofosbuvir y daclatasvir y sofosbuvir y ledipasvir alcanzanel 100% de respuesta en no respondedores a triple terapiacon boceprevir y telaprevir.Conclusiones: Las nuevas generaciones de AAD frente al VHCvan a suponer un aumento de las tasas de curación en todoslos subtipos de pacientes, a través de regímenes más sencillosy mejor tolerados.

Palabras clave


Hepatitis C crónica; Terapia; Agente antiviral directo

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Referencias


Poynard T, Yuen M-F, Ratziu V, Lai CL. Viral hepatitis C. Lancet. 2003 Dec 20;362(9401):2095–100.

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958–65.

Thomas DL. Advances in the treatment of hepatitis C virus infection. Top Antivir Med. 2012 May;20(1):5–10.

http://www.ema.europa.eu/ema/.

www.fda.gov.

Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1207–17.

Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1195–206.

Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011 Jun 23;364(25):2405–16.

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009 Aug 6;361(6):580–93.

Chopra A, Klein PL, Drinnan T, Lee SS. How to optimize HCV therapy in genotype 1 patients: management of side-effects. Liver Int Off J Int Assoc Study Liver. 2013 Feb;33 Suppl 1:30–4.

Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature. 2010 May 6;465(7294):96–100.

Pol S, Ghalib RH, Rustgi VK, Martorell C, Everson GT, Tatum HA, et al. Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial. Lancet Infect Dis. 2012 Sep;12(9):671–7.

Lam AM, Murakami E, Espiritu C, Steuer HMM, Niu C, Keilman M, et al. PSI-7851, a pronucleotide of beta-D-2’-deoxy-2’-fluoro-2’-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication. Antimicrob Agents Chemother. 2010 Aug;54(8):3187–96.

Label information Sofosbuvir. FDA. 2013. [citado 10/12/2013]. Disponible en: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204671s000lbl.pdf.

Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34–44.

Lawitz E, Lalezari JP, Hassanein T, Kowdley KV, Poordad FF, Sheikh AM, et al. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2013 May;13(5):401–8.

Kowdley KV, Lawitz E, Crespo I, Hassanein T, Davis MN, DeMicco M, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet. 2013 Jun 15;381(9883):2100–7.

Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013 May 16;368(20):1878–87.

Osinusi A, Meissner EG, Lee Y-J, Bon D, Heytens L, Nelson A, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA J Am Med Assoc. 2013 Aug 28;310(8):804–11.

Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013 May 16;368(20):1867–77.

Manns MP, Bourlière M, Benhamou Y, Pol S, Bonacini M, Trepo C, et al. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol. 2011 Jun;54(6):1114–22.

Sulkowski MS, Asselah T, Lalezari J, Ferenci P, Fainboim H, Leggett B, et al. Faldaprevir combined with pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic genotype 1 HCV: SILEN-C1 trial. Hepatol Baltim Md. 2013 Jun;57(6):2143–54.

Sulkowski MS, Bourlière M, Bronowicki J-P, Asselah T, Pawlotsky J-M, Shafran SD, et al. Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial. Hepatol Baltim Md. 2013 Jun;57(6):2155–63.

Nishiguchi S, Sakai Y, Kuboki M, Tsunematsu S, Urano Y, Sakamoto W, et al. Safety and efficacy of faldaprevir with pegylated interferon alfa-2a and ribavirin in Japanese patients with chronic genotype-1 hepatitis C infection. Liver Int Off J Int Assoc Study Liver. 2014 Jan;34(1):78–88.

HIVandHEPATITIS.com. San Francisco. [citado el 10/12/2013]. Disponible en: http://hivandhepatitis.com/hcv-treatment/experimental-hcv-drugs/4429-aasld-2013-faldaprevir-triple-therapy-effective-across-patient-subgroups.

Manns M, Reesink H, Berg T, Dusheiko G, Flisiak R, Marcellin P, et al. Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial. Antivir Ther. 2011;16(7):1021–33.

Hayashi N, Seto C, Kato M, Komada Y, Goto S. Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1-infected patients in Japan: the DRAGON study. J Gastroenterol. 2013 Sep 5;

Fried MW, Buti M, Dore GJ, Flisiak R, Ferenci P, Jacobson I, et al. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: The randomized PILLAR study. Hepatol Baltim Md. 2013 Dec;58(6):1918–29.

Zeuzem S, Berg T, Gane E, Ferenci P, Foster GR, Fried MW, et al. Simeprevir Increases Rate of Sustained Virologic Response Among Treatment-Experienced Patients With HCV Genotype-1 Infection: A Phase IIb Trial. Gastroenterology. 2013 Nov 1;

Manns MP, Gane E, Rodriguez-Torres M, Stoehr A, Yeh C-T, Marcellin P, et al. Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: a randomized phase II study. Hepatol Baltim Md. 2012 Sep;56(3):884–93.

Lawitz E, Rodriguez-Torres M, Stoehr A, Gane EJ, Serfaty L, Bhanja S, et al. A phase 2B study of MK-7009 (vaniprevir) in patients with genotype 1 HCV infection who have failed previous pegylated interferon and ribavirin treatment. J Hepatol. 2013 Jul;59(1):11–7.

Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012 Jan 19;366(3):216–24.

Suzuki Y, Ikeda K, Suzuki F, Toyota J, Karino Y, Chayama K, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2013 Apr;58(4):655–62.

Everson GT, Sims KD, Rodriguez-Torres M, Hézode C, Lawitz E, Bourlière M, et al. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterology. 2014 Feb;146(2):420–9.

Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211–21.

Nakamoto S, Kanda T, Wu S, Shirasawa H, Yokosuka O. Hepatitis C virus NS5A inhibitors and drug resistance mutations. World J Gastroenterol WJG. 2014 Mar 21;20(11):2902–12.

Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515–23.

Zeuzem S, Asselah T, Angus P, Zarski J-P, Larrey D, Müllhaupt B, et al. Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results. Antivir Ther. 2013;18(8):1015–9.

Zeuzem S, Soriano V, Asselah T, Bronowicki J-P, Lohse AW, Müllhaupt B, et al. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med. 2013 Aug 15;369(7):630–9.

Poordad F, Lawitz E, Kowdley KV, Cohen DE, Podsadecki T, Siggelkow S, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):45–53.

Lawitz E, Poordad F, Kowdley KV, Cohen DE, Podsadecki T, Siggelkow S, et al. A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1. J Hepatol. 2013 Jul;59(1):18–23.

Hézode C. Boceprevir and telaprevir for the treatment of chronic hepatitis C: safety management in clinical practice. Liver Int Off J Int Assoc Study Liver. 2012 Feb;32 Suppl 1:32–8.

Chayama K, Suzuki Y, Ikeda K, Toyota J, Karino Y, Kawasaki Y et al. All-oral Combination of Daclatasvir Plus Asunaprevir in Interferon Ineligible Naive/Intolerant and Nonresponder Japanese Patients Chronically Infected with HCV Genotype 1b: Results from a Phase 3 Trial. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington, DC, November 1-5, 2013. Abstract211.




DOI: http://dx.doi.org/10.7399%2Ffh.2014.38.3.7314

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