Efficacy, Safety and UK Cost-Effectiveness in Treatment-Naive Patients with F2 Fibrosis Treated with Telaprevir (TVR; T) in Combination with Peginterferon (P) and Ribavirin (R) vs Peginterferon and Ribavirin Alone

Abstract

Purpose: In their deliberations about whether to initiate protease-inhibitor based therapy in patients with genotype 1 HCV infection, clinicians place considerable reliance upon whether patients have mild or advanced fibrosis. Patients with Metavir F2 present a particular challenge as they fall in the intermediate range of degree of fibrosis. In this post-hoc analysis of the Phase III ADVANCE study, the efficacy, safety and cost-effectiveness of TPR vs PR in treatment-naïve genotype 1 HCV-infected patients with F2 fibrosis are reported to assess the value of treating F2 patients with TPR. Methods: Baseline (BL) characteristics, virologic response and safety were analyzed in the F2 subset of T12PR (PR for 24 or 48 weeks) (N=156) and PR48 (N=141) patients in the ADVANCE study. Fibrosis stage was assessed using the Metavir scoring system. Number Needed to Treat (NNT) was derived as the inverse of the difference in absolute efficacy response (TPR - PR). Cost-effectiveness of TPR vs PR in F2 patients was determined based on a UK economic model (costs estimated in UK £s). Results: Overall, 41% (297/724) of patients randomized to TPR or PR48 had F2 fibrosis at study entry. BL characteristics were well-balanced across treatment arms (Table). Virologic response rates were statistically (p<0.0001) higher with TPR vs PR within the F2 subgroup. Using SVR24, NNT in F2 patients was estimated to be 3.3, i.e. ˜3 patients would need to be treated with TPR to obtain 1 additional cure vs treatment with PR alone. In F2 patients, TVR was associated with higher costs and improved outcomes relative to PR, resulting in an Incremental Cost Effectiveness Ratio (ICER) of £9930/Quality Adjusted Life Year (QALY). Conclusion: In this post-hoc analysis of HCV-infected, treatment-naïve patients from the ADVANCE trial with F2 fibrosis, higher efficacy of TPR vs PR and a favorable NNT to obtain an additional cure were observed. In addition, in F2 patients, TPR was cost-effective vs PR. The large number of F2 patients in the HCV-infected population represents an opportunity for a substantial number of additional cures with TPR vs PR alone. Disclosure: Ira M Jacobson: Grant/Research support: Achillion, Anadys, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, GlobeImmune, Novartis, Pfizer, Pharmasset, Roche/Genentech, Schering/Merck, Tibotec/Janssen, Vertex, Zymogenetics; Consulting: Abbott, Achillion, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Glaxo Smithkline, GlobeImmune, Inhibitex, Idenix, Kadmon, Novartis, Pharmasset, Presidio, Roche/Genentech, Schering/Merck, Tibotec/Janssen, Vertex; Speakers Bureau: Bristol Myers Squibb, Gilead, Roche/Genentech, Schering/Merck, Vertex. Alessandra Baldini, Ralph DeMasi, Sandra Gavart, Donghan Luo, Joseph Mrus and James Witek are all full-time employees of Janssen. Patrick Marcellin is a speaker and investigator for BMS, Boehring-Ingelheim, Tibotec, Janssen, Gilead, Roche and Merck. This research was supported by an industry grant from The ADVANCE trial was supported by Janssen Infectious Diseases BVBA and Vertex Pharmaceuticals Incorporated.Figure: †FDA Snapshot analysis; ‡Any Rash Special Search Categories (SSC) clinical AE; SVR = sustained virologic response.