Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
ACCURATE PERSONALIZATION OF PEG-IFN+RBV TREATMENT DURATION BASED ON THE DECLINE OF HCV INFECTED CELLS COMPUTED DURING THE 1ST MONTH OF THERAPY
P. Colombatto1*, V. Romagnoli1, L. Civitano1, P. Ciccorossi1, A.M. Maina1, F. Oliveri1, B. Coco1, B. Cherubini1, F. Bonino2,3, M.R. Brunetto1
1University Hospital of Pisa, 2University of Pisa, Pisa, 3Foundation IRCCS “Policlinico” of Milan, Milano, Italy. *email@example.com
Background and aims: According to HCV-RNA decline at week 4 and 12 PegIFN+RBV therapy can be shortened (12-24 weeks) or prolonged (48-72 weeks) to improve its cost-efficacy. Modelling the decline of the infected cells may allow for a more accurate calculation of treatment duration. We tested in a randomised controlled trial (EudraCT registration # 2006−002483−26) duration and efficacy of model tailored (MT) vs Guide Line (GL) approaches.
Patients and methods: One hundred consecutive patients (38 naïve - 62 retreated, 60 Genotype1-4 and 40 Genotype2-3, 60 peg-IFN 2a and 40 2b), were stratified and randomised 1:1 to receive GL or MT schedules. GL patients were treated for 24 weeks if Genotype2-3 and for 48 weeks if Genotype1-4 applying the week 12 stopping rule in Genotype1 non responders (NR). MT patients had ALT and HCV-RNA measured at day 0-2-4-7-14-21-28 to compute the infected cell number at the end of therapy (Ieot): if Ieot>5000 at GL duration treatment was stopped (week 6), otherwise tailored to achieve Ieot< 250.
Results: Leot could be computed in 42 (84%) MT patients, the remaining 8 were switched to GL schedules (not included in this analysis). Therapy was withdrawn/modified because of side effects in 13 (26%) MT and in 9 (18%) GL patients; 11 (22%) MT and 8 (16%) GL patients were NR. Per protocol analysis showed SVR rates of 85% in MT and 82% in GL schedules. Individual treatment durations in MT SVR patients ranged between 18-55 weeks in 7 Genotype1, 13-21 weeks in 3 Genotype2 and 21-56 weeks in 5 Genotype3 patients. In GL patients who completed therapy the treatment required for SVR was 21% longer than in MT patients.
Conclusions: The duration of the antiviral treatment can be calculated with accuracy at the single patient level by modelling the decline of the infected cells. By this approach we showed that the treatment required to achieve an SVR is widely variable among patients and only in part related to the HCV Genotype. Optimization in larger studies of the Ieot threshold used to tailor duration might further improve the cost-efficacy of this personalized approach.