A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients: The TT4 randomized trial

Digestive and Liver Disease

Available online 13 November 2013

In Press, Corrected Proof — Note to users

Liver, Pancreas and Biliary Tract

Simona Francioso^a,  Cristiana Almerighi^a, Paolo Forte^b, Franco Bandiera^c,  Lorenzo Nosotti^d,  Raffaella Lionetti^e, Gloria Taliani^f, Maria Rosaria Piras^g, Maria Laura Ponti^g, Giustino Parruti^h, Francesco Di Candiloⁱ, Silvia Gentile^a, Paola Piccolo^a, Angela Salso^a, Francesca Riccobelli^a, Sara Renzi^b, Maria Antonella Longo^e, Marzia Montalbano^e, Salvatore Zaru^c, Elisa Biliotti^f, Francesco Di Masi^h, Francesco Santopaolo^a, Mario Angelico^a

a Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
b G. Careggi Hospital, University of Florence, Italy
c SS Annunziata Hospital, Sassari, Italy
d National Institute for Health Migration and Poverty (NIHMP), Rome, Italy
e National Institute of Infectious Diseases, L. Spallanzani Hospital, Rome, Italy
f Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy
g G. Brotzu Hospital, Cagliari, Italy
h Ospedale Civile, Pescara, Italy
i S.M. Misericordia Hospital, Perugia, Italy

Abstract

Background Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4).

Method 267 naïve HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n = 180) or current standard-of-care (SoC, n = 87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2 log₁₀ at week 12 or detectable HCV-RNA at week 24 discontinued treatment.

Results Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25 ± 15 vs. 36 ± 12.1 weeks], and for subgroups: G1 [35.3 ± 16.7 vs. 47.3 ± 2.6 weeks], G2 [18.3 ± 7.5 vs. 24 ± 2.8 weeks], G3 [15.2 ± 8.7 vs. 22.8 ± 3 weeks] and G4 [26.9 ± 13 vs. 48 weeks].

Conclusions In HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction.

Keywords HCV treatment; Dual therapy; Pegylated interferon; Ribavirin; Rapid viral response; Response-guided therapy; Individualized therapy

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