Mini review

Dermatological adverse effects during genotype-1 hepatitis C treatment with the protease inhibitors telaprevir and boceprevir. Patient management

Telaprevir es un fármaco que administrado junto a interferón y ribavirina incrementa de forma significativa la respuesta al tratamiento de la infección por el virus de la hepatitis C. Sin embargo, su empleo incrementa también la probabilidad de desarrollar efectos adversos, en muchos casos cutáneos que pueden condicionar el mantenimiento del tratamiento.

Conocer la incidencia, características clínicas y evolutivas y respuesta al tratamiento de las toxicodermias por telaprevir en el contexto del tratamiento de la infección por el virus de la hepatitis C.

Estudio prospectivo observacional realizado entre mayo de 2012 y julio de 2013 en el que se incluyeron aquellos pacientes que iniciaron tratamiento con telaprevir durante ese periodo. En aquellos en los que se detectaron toxicodermia se recogieron los datos demográficos de los pacientes, las características clínicas de las lesiones y la evolución tras la aplicación de las recomendaciones de las guías clínicas.

De un total de 43 pacientes que recibieron tratamiento triple un 46% presentó toxicodermia atribuible a telaprevir. En el 90% de los casos esta fue leve o moderada (grados 1 o 2) y consistió en un exantema constituido por pápulas y placas eritematoedematosas y descamativas. En alrededor de un tercio de los pacientes se comprobó la progresión de la toxicodermia, principalmente en extensión, durante el curso del tratamiento. En 2 casos (4,6%) las lesiones cutáneas condicionaron la suspensión del fármaco. Un 79% de los tratados (34 pacientes) alcanzó una respuesta viral sostenida tras el tratamiento.

Las toxicodermias asociadas a telaprevir son frecuentes en el curso del tratamiento y a menudo progresivas. Sin embargo, solo de forma excepcional condicionan su suspensión.

When co-administered with interferon and ribavirin, the prescription drug telaprevir significantly improves treatment response in patients with chronic hepatitis C virus (HCV) infection. Its use, however, also increases the likelihood of adverse effects that may lead to discontinuation of treatment. Cutaneous adverse effects are particularly common.

To determine the frequency and clinical characteristics of drug eruptions induced by telaprevir in patients receiving HCV treatment and to analyze the clinical course of lesions and response to treatment.

We performed a prospective observational study of all patients who started a treatment regimen that included telaprevir between May 2012 and July 2013. We recorded the demographic characteristics of the patients who developed telaprevir-induced eruptions, and analyzed the clinical characteristics of the lesions and their clinical course following the application of guideline-based treatment recommendations.

Twenty (46%) of the 43 patients who received triple therapy with interferon, ribavirin, and telaprevir during the study period developed drug reactions attributable to telaprevir. The reaction was classified as mild or moderate (grades 1 or 2) in 90% of cases and consisted of an exanthem with erythematous-edematous scaling plaques and papules. The rash worsened, mainly by spreading, in about one-third of cases. The skin lesions led to discontinuation of treatment in 2 patients (4.6%). Sustained viral response was achieved in 34 patients (79%).

Telaprevir-induced eruptions are common and often progress, but they rarely require patients to discontinue treatment.

The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient’s baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism.

Hepatitis C virus (HCV) infection is curable by therapy. The antiviral treatment of chronic hepatitis C has been based for decades on the use of interferon (IFN)-α, combined with ribavirin. More recently, new therapeutic approaches that target essential components of the HCV life cycle have been developed, including direct-acting antiviral (DAA) and host-targeted agents (HTA). A new standard-of-care treatment has been approved in 2011 for patients infected with HCV genotype 1, based on a triple combination of pegylated IFN-α, ribavirin, and either telaprevir or boceprevir, two inhibitors of the HCV protease. New triple and quadruple combination therapies including pegylated IFN-α, ribavirin, and one or two DAAs/HTAs, respectively, are currently being evaluated in Phase II and III clinical trials. In addition, various options for all-oral, IFN-free regimens are currently being evaluated. This chapter describes the characteristics of the different drugs used in the treatment of chronic hepatitis C and those currently in development and provides an overview of the current and future standard-of-care treatments of chronic hepatitis C.