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

Simona Francioso, Cristiana Almerighi, Paolo Forte, Franco Bandiera, Lorenzo Nosotti, Raffaella Lionetti, Gloria Taliani, Maria Rosaria Piras, Maria Laura Ponti, Giustino Parruti, Francesco Di Candilo, Silvia Gentile, Paola Piccolo, Angela Salso, Francesca Riccobelli, Sara Renzi, Maria Antonella Longo, Marzia Montalbano, Salvatore Zaru, Elisa BiliottiFrancesco Di Masi, Francesco Santopaolo, Mario Angelico

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 ≤2log10 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.

Original languageEnglish
Pages (from-to)164-169
Number of pages6
JournalDigestive and Liver Disease
Volume46
Issue number2
DOIs
Publication statusPublished - Feb 2014

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Chronic Hepatitis C
Hepacivirus
Genotype
Ribavirin
RNA
Therapeutics
Virus Diseases
Standard of Care
Liver Diseases
Costs and Cost Analysis
Recurrence
Population

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients : The TT4 randomized trial. / Francioso, Simona; Almerighi, Cristiana; Forte, Paolo; Bandiera, Franco; Nosotti, Lorenzo; Lionetti, Raffaella; Taliani, Gloria; Piras, Maria Rosaria; Ponti, Maria Laura; Parruti, Giustino; Di Candilo, Francesco; Gentile, Silvia; Piccolo, Paola; Salso, Angela; Riccobelli, Francesca; Renzi, Sara; Longo, Maria Antonella; Montalbano, Marzia; Zaru, Salvatore; Biliotti, Elisa; Di Masi, Francesco; Santopaolo, Francesco; Angelico, Mario.

In: Digestive and Liver Disease, Vol. 46, No. 2, 02.2014, p. 164-169.

Research output: Contribution to journalArticle

Francioso, S, Almerighi, C, Forte, P, Bandiera, F, Nosotti, L, Lionetti, R, Taliani, G, Piras, MR, Ponti, ML, Parruti, G, Di Candilo, F, Gentile, S, Piccolo, P, Salso, A, Riccobelli, F, Renzi, S, Longo, MA, Montalbano, M, Zaru, S, Biliotti, E, Di Masi, F, Santopaolo, F & Angelico, M 2014, '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, vol. 46, no. 2, pp. 164-169. https://doi.org/10.1016/j.dld.2013.10.002
Francioso, Simona ; Almerighi, Cristiana ; Forte, Paolo ; Bandiera, Franco ; Nosotti, Lorenzo ; Lionetti, Raffaella ; Taliani, Gloria ; Piras, Maria Rosaria ; Ponti, Maria Laura ; Parruti, Giustino ; Di Candilo, Francesco ; Gentile, Silvia ; Piccolo, Paola ; Salso, Angela ; Riccobelli, Francesca ; Renzi, Sara ; Longo, Maria Antonella ; Montalbano, Marzia ; Zaru, Salvatore ; Biliotti, Elisa ; Di Masi, Francesco ; Santopaolo, Francesco ; Angelico, Mario. / A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients : The TT4 randomized trial. In: Digestive and Liver Disease. 2014 ; Vol. 46, No. 2. pp. 164-169.
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T1 - A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients

T2 - The TT4 randomized trial

AU - Francioso, Simona

AU - Almerighi, Cristiana

AU - Forte, Paolo

AU - Bandiera, Franco

AU - Nosotti, Lorenzo

AU - Lionetti, Raffaella

AU - Taliani, Gloria

AU - Piras, Maria Rosaria

AU - Ponti, Maria Laura

AU - Parruti, Giustino

AU - Di Candilo, Francesco

AU - Gentile, Silvia

AU - Piccolo, Paola

AU - Salso, Angela

AU - Riccobelli, Francesca

AU - Renzi, Sara

AU - Longo, Maria Antonella

AU - Montalbano, Marzia

AU - Zaru, Salvatore

AU - Biliotti, Elisa

AU - Di Masi, Francesco

AU - Santopaolo, Francesco

AU - Angelico, Mario

PY - 2014/2

Y1 - 2014/2

N2 - 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 ≤2log10 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.

AB - 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 ≤2log10 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.

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KW - HCV treatment

KW - Individualized therapy

KW - Pegylated interferon

KW - Rapid viral response

KW - Response-guided therapy

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