Impact of PegIntron (PEG) Maintenance Therapy (MT) on Fibrosis Biomarkers (FibroTest (FT)/FibroSURE) in Prior Nonresponders With METAVIR Fibrosis Scores (MFS) of F2/F3: Final Results From the EPIC 3 Program

Background & Aims: The EPIC 3 F2/3 study, designed to evaluate the efficacy of low dose PEG-2b (0.5 mcg/kg/week) MT vs observation (OBS) on improvement of MFS in previous nonresponders did not demonstrate efficacy of MT. The aim of the present study was to assess if there was a treatment effect on FT and Actitest (AT), two validated sensitive non-invasive markers of fibrosis with similar prognostic values, compared to liver biopsy (LBx) (FT: FibroTest, AT: necroinflammatory activity). Methods: Patients with F2/F3 MFS who failed retreatment (ReRx) were randomized to PEG or OBS for 36 months. Blinded LBx obtained before ReRx and after MT were evaluated using MFS and MAS. FT-AT were blindly assessed using predetermined cutoffs. The primary biochemical endpoint was the percentage of patients who did not progress at least 0.20 for FT or 0.25 for AT corresponding to 1 MFS and 1 activity grade respectively, at the last assay in comparison with baseline. Results: Of 539 randomized, 357 were included, 182 not included (170 with 600,000IU/mL, and 94% genotype 1, median FT 0.67, AT 0.62. Using FT equivalence of MFS, significantly more patients worsened in OBS vs PEG (14% vs 6%; P = .02) and using AT equivalence more PEG patients improved in activity METAVIR grade AS vs OBS (16% vs 5%; P =.001). There was significant worsening in fibrosis estimated using last FT, in controls vs patients treated with PEG, as well as for necro-inflammatory activity estimated using last AT (table). Impact by time is in Table. Conclusions: Using biomarkers this randomized trial demonstrated improvement of both fibrosis and necroinflammatory estimates with PEG maintenance therapy. Due to the risk of under powered conclusions, using biopsy as the main endpoint in maintenance therapy clinical trials should be revisited. Table. Fibrotest and Actitest over Time (mean change from baseline; 95%CI)