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 peginter-feron alfa-2a/ribavirin.
Bibliographical noteFunding Information:
The authors of this manuscript have the following competing interests: G. R. Foster reports Speaker and consultancy fees from Roche, Merck, Gilead Sciences, Novartis, AbbVie, Janssen, Bristol-Myers Squibb, Boehringer Ingelheim, Idenix, Achillion. C. Coppola and M. Derbala report no competing interests. P. Ferenci reports the following interests: Global Advisory board: Roche/Genentech, Merck; Advisor: AbbVie, Gilead Sciences, Janssen, Achillion; Speaker’s bureau: Roche, MSD Austria, Janssen Austria, BMS Austria, Gilead Sciences, AbbVie, Boehringer Ingelheim; Unrestricted research grant: Roche Austria. A. Orlandini reports no competing interests. K.R. Reddy reports the following interests: Advisory Board: Merck, Gilead Sciences, AbbVie, Bristol-Myers Squibb, Genentech-Roche, Idenix, Novartis, Janssen, Vertex. Research Support: Merck, Gilead, Bristol-Myers Squibb, AbbVie, Janssen, Vertex. L. Tallarico has no competing interests. M.L. Shiffman has the following interests: Advisory board: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Hologic, Janssen, Merck, Novartis, Roche/Genentech and Vertex; Grant support from AbbVie, Achillion, Beckman-Colter, Bristol-Myers Squibb, Boehringer Ingelheim, Conatus, Gilead Sciences, Hologic, Intercept, Lumena, Merck and Novartis; and speaker fees from Abbvie, Bayer, Bristol-Myers Squibb, Gilead, Janssen, Merck, Roche/Genentech and Vertex. S. Ahlers is an employee of PROMETRIS GmbH the clinical research organization providing data management and statistical services to Roche. G. Bakalos is an employee of F. Hoffmann-La Roche Ltd, Basel, Switzerland. T. Hassanein has reveived the following Research Grants: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Gilead Sciences, Idenix, Ikaria, Janssen, La Jolla Pharmaceuticals, Merck, Mochida, NGM BioPharmaceuticals, Roche, Ocera, Sundise, Salix, TaiGen, Takeda, Tobria, Vertex, Vital Therapies. He is also on the following advisory boards: AbbVie, Bristol-Myers Squibb. Speaker: Baxter, Bristol-Myers Squibb, Gilead Sciences, Salix. Peginterferon alfa-2a (PEGASYS®) and ribavirin (COPEGUS®) are both products marketed by F. Hoffmann-La Roche, Basel, Switzerland and protected by various intellectual property rights. There are no other patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
The authors thank Fernando Tatsch for his contributions to the initiation and set-up of this study while in the employment of F. Hoffmann-La Roche Ltd, Basel, Switzerland. This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
© 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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