title: [Cutaneous adverse events of telaprevir/peginterferon/ribavirin therapy for chronic hepatitis C: A multicenter prospective cohort study].
abstract: BACKGROUND
  Telaprevir, sale of which was suspended, has been approved in combination with pegylated interferon and ribavirin (triple therapy) in the treatment of chronic hepatitis C virus (HCV). Skin eruptions and isolated cases of severe cutaneous adverse reactions (SCAR) have been reported.
  
  
  OBJECTIVE
  Our aim was to assess the incidence of skin eruption and the clinical characteristics of mucocutaneous adverse events (AE), and to identify potential risk factors for telaprevir-associated skin eruption.
  
  
  METHODS
  A prospective observational multicenter follow-up cohort study with monthly controls by a dermatologist and additional examinations in case of any undercurrent AE.
  
  
  RESULTS
  Among the 48 enrolled patients, the incidence of skin eruption was 58.4%, consisting mainly of maculopapular and eczematous lesions and only one case of SCAR. Telaprevir was discontinued in 6% of patients due to severe rash, whereas peginterferon and ribavirin were continued. The median time to onset of rash following telaprevir initiation was 25 days (range: 3-79 days). The rash was preceded by skin dryness and associated with pruritus in 100% and 90% of patients, respectively. Of those presenting with skin eruption, 37.5% also complained of conjunctival or oral lesions, or of anorectal symptoms. Neither a past history of dermatological conditions nor sociodemographic or viral status was predictive factor for skin rash.
  
  
  CONCLUSIONS
  Telaprevir-related dermatitis has a high incidence but is mostly of mild intensity. In most cases, tri-therapy was continued under close dermatological follow-up allowing rapid detection of rare instances of severe drug eruptions. Ribavirin and Interferon were thus continued even in the event of diffuse eruptions, enabling confirmation of the causative role of telaprevir in these eruptions.
authors.affiliation: Inserm CRO2, UMR 911, service de dermatologie et de cancérologie cutanée, hôpital de la Timone, Aix-Marseille université, AP-HM, 264, rue Saint-Pierre, 13385 Marseille cedex 5, France.
authors.forename: S
authors.initials: S
authors.lastname: Lorcy
authors.affiliation: Inserm CRO2, UMR 911, service de dermatologie et de cancérologie cutanée, hôpital de la Timone, Aix-Marseille université, AP-HM, 264, rue Saint-Pierre, 13385 Marseille cedex 5, France. Electronic address: caroline.gaudy@ap-hm.fr.
authors.forename: C
authors.initials: C
authors.lastname: Gaudy-Marqueste
authors.affiliation: Service d'hépato-gastroentérologie, hôpital Conception, Aix-Marseille université, AP-HM, 147, boulevard Baille, 13005 Marseille, France.
authors.forename: D
authors.initials: D
authors.lastname: Botta
authors.affiliation: Service d'hépato-gastroentérologie, hôpital Conception, Aix-Marseille université, AP-HM, 147, boulevard Baille, 13005 Marseille, France.
authors.forename: I
authors.initials: I
authors.lastname: Portal
authors.affiliation: Service de dermatologie, hôpital Saint-Joseph, 26, boulevard de Louvain, 13285 Marseille, France.
authors.forename: N
authors.initials: N
authors.lastname: Quiles
authors.affiliation: Service d'hépato-gastroentérologie, hôpital Saint-Joseph, 26, boulevard de Louvain, 13285 Marseille, France.
authors.forename: V
authors.initials: V
authors.lastname: Oulies
authors.affiliation: Inserm, IRD, SESSTIM, service de santé publique et d'information médicale, hôpital de la Timone, Aix-Marseille université, AP-HM, 13385 Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Mancini
authors.affiliation: Inserm CRO2, UMR 911, service de dermatologie et de cancérologie cutanée, hôpital de la Timone, Aix-Marseille université, AP-HM, 264, rue Saint-Pierre, 13385 Marseille cedex 5, France.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Grob
authors.affiliation: Inserm CRO2, UMR 911, service de dermatologie et de cancérologie cutanée, hôpital de la Timone, Aix-Marseille université, AP-HM, 264, rue Saint-Pierre, 13385 Marseille cedex 5, France.
authors.forename: M-A
authors.initials: MA
authors.lastname: Richard
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003875:Drug Eruptions / Q000209:etiology*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a
keywords: Drug eruption; Effets secondaires; Hepatitis C; Hépatite C; Interferon; Interféron; Ribavirin; Ribavirine; Side effects; Telaprevir; Toxidermie; Télaprévir