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Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

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Foster, Graham R Coppola, Carmine Derbala, Moutaz Ferenci, Peter Orlandini, Alessandra Horsmans, Yves [UCL]

(eng) BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin. TRIAL REGISTRATION: ClinicalTrials.gov NCT01344889.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2016
Language Anglais
Journal information "PLoS One" - Vol. 11, no. 3, p. e0151703 [1-20] (2016)
Peer reviewed yes
Publisher Public Library of Science ((United States) San Francisco, CA)
e-issn 1932-6203
Publication status Publié
Affiliations UCL - SSS/IREC-Institut de recherche expérimentale et clinique
UCL - SSS/IREC/GAEN-Pôle d'Hépato-gastro-entérologie
UCL - (SLuc) Service d'hépato-gastro-entérologie
MESH Subject Adult ; Hepacivirus ; Hepatitis C, Chronic ; Host-Pathogen Interactions ; Humans ; Interferon-alpha ; Male ; Middle Aged ; Neutropenia ; Outcome Assessment (Health Care) ; Polyethylene Glycols ; Aged ; Proportional Hazards Models ; RNA, Viral ; Recombinant Proteins ; Ribavirin ; Withholding Treatment ; Anemia ; Antiviral Agents ; Asthenia ; Cohort Studies ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female
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Bibliographic reference Foster, Graham R ; Coppola, Carmine ; Derbala, Moutaz ; Ferenci, Peter ; Orlandini, Alessandra ; et. al. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.. In: PLoS One, Vol. 11, no. 3, p. e0151703 [1-20] (2016)
Permanent URL http://hdl.handle.net/2078.1/180115