Objective We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.
Design Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).
Results Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.
Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.
Trial registration number NCT0209966.
- ANTIVIRAL THERAPY
- CHRONIC VIRAL HEPATITIS
- HEPATITIS C
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Collaborators All collaborators are listed in online supplementary table S6.
Contributors All programme participants are listed in online supplementary table S6. MJJ-E developed the concept and design of the programme. TMW, JP, KH, PF, MG, HW, TB, US, OW, MvdV, JR, MP-R and SZ acquired the data. YZ and MJJ-E analysed the data. All authors participated in data interpretation, manuscript preparation and critical review and approved the final version of the manuscript.
Funding This CUP was funded by Bristol-Myers Squibb. Editorial assistance was provided by Richard Boehme of Articulate Science and funded by Bristol-Myers Squibb.
Competing interests TMW—consultant: Novartis, Janssen, Gilead, AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb. JP—grant: Roche, GlaxoSmithKline; consultant: Bristol-Myers Squibb, Gilead, Novartis, Merck; speaking and teaching: Abbott, Tibotec, Merck. PF—consultant: Idenix, Gilead, Merck, Janssen, Salix, AbbVie, Bristol-Myers Squibb; patent held/filed: Madaus Rottapharm; speaking and teaching: Gilead, Roche. MG—consultant: Janssen, Bristol-Myers Squibb, Gilead, AbbVie; speaking and teaching: Janssen, Bristol-Myers Squibb, Gilead, AbbVie. HW—grant: Merck, Novartis, Gilead, Roche, Abbott, AbbVie; speaking and teaching: Bristol-Myers Squibb, Merck, Novartis, Italfarmaco, AbbVie, Gilead; advisory committee or review panel: Transgene, Merck, Roche, Gilead, Abbott, AbbVie, Bristol-Myers Squibb, Falk, Novartis, GlaxoSmithKline. TB—grant: Gilead, Bristol-Myers Squibb, Roche, Tibotec, Vertex, Janssen, Merck, Boehringer Ingelheim, Novartis, AbbVie; consultant: Gilead, Bristol-Myers Squibb, Roche, Tibotec, Vertex, Janssen, Novartis, Abbott, Merck, AbbVie; speaking and teaching: Gilead, Bristol-Myers Squibb, Roche, Tibotec, Vertex, Janssen, Merck, Novartis, Bayer, AbbVie. OW—speakers' bureau: Merck, Roche, Bristol-Myers Squibb, Novartis, Janssen, Medivir, Gilead, AbbVie; consultant: Merck, Bristol-Myers Squibb, Medivir, Gilead, AbbVie. MvdV—consultant: Gilead, Merck, Bristol-Myers Squibb, AbbVie, Janssen, ViiV Healthcare, Roche. JR—grant: Merck; consultant: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Roche, Tibotec, Bionor, Tobira, ViiV Healthcare, Gilead, Janssen, Novartis; speaking and teaching: Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Roche, Tibotec, Gilead, Janssen, ViiV Healthcare. MP-R—grant: Bayer, Roche, Gilead, Merck, AbbVie; consultant: Bayer, Boehringer Ingelheim, Jennerex, Eli Lilly, AbbVie; advisory committee or review panel: Bayer, Gilead, Janssen, Bristol-Myers Squibb, AbbVie; speaking and teaching: Bayer, Roche, Gilead, Merck, Eli Lilly, AbbVie. YZ—employee: Bristol-Myers Squibb. MJJ-E—employee: Bristol-Myers Squibb. SZ—consultant: AbbVie, Bristol-Myers Squibb, Gilead, Merck, Janssen.
Patient consent Obtained.
Ethics approval This programme was approved by national health authorities for all participating countries. Ethics committee approval was managed by participating sites on an individual basis in accordance with local legislation regulating CUPs.
Provenance and peer review Not commissioned; externally peer reviewed.
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