- Email: [email protected]
247 PREDICTING TREATMENT OUTCOME AMONG SLOW RESPONDERS: A RETROSPECTIVE ANALYSIS OF THE SUCCESS STUDY
POSTERS who were stable on substitution therapy and well motivated, could be referred to the hepatologist. During therapy the hospital pharmacy monitored adherence, the addiction centers provided substitution maintenance therapy. In problematic cases intensive communication between the hepatology service and the addiction center was organised. Results: In 549 HCV-ab + patients referred to the hepatology unit, encompassing 338 IVDUs (62%) and 211 non-IVDUs, 257 (76%) IVDUs and 156 (74%) non-IVDUs were HCV-RNA positive. In 214 IVDUs and 118 non-IVDUs with elevated serum transaminases resp. 125 (58%) and 79 (67%) started antiviral medication. There was no difference in the rate of treatment start between the two groups: the main reasons in IVDUs for not starting were: uncontrolled alcohol (n = 14–15%) and substance abuse (n = 2–2%), uncontrolled psychiatric disease (n = 3–3%) with suicidal ideation (n = 1), social problems (n = 7–7%), imprisonment (5–5%). In the treated population, 79% of the IVDUs was male versus 58% among the non-IVDUs. Median age was resp. 35 and 41 y, with a median viral load of resp. 2.17 and 1.48. Using intention-to-treat analysis, SVR was obtained in 79 (63%) of the IVDUs versus 38 (48%) of the non-IVDUs (p = 0.03). Conclusion: A very high uptake and SVR can be obtained in chronic hepatitis C patients infected after substance use in a nonunder one roof multidisciplinary collaboration. Especially intense collaboration and not the location of the management is of importance. 246 ASSESSMENT OF PAROXETINE IN THE PREVENTION OF DEPRESSION IN PATIENTS WITH CHRONIC HEPATITIS C TREATED BY PEG-INTERFERON-RIBAVIRIN.: A DOUBLE-BLINDED, RANDOMIZED STUDY. ANRS HC18 PAROPEG J.-P. Bronowicki1 , V. Canva2 , A. Tran3 , M.-N. Hilleret4 , S. Pol5 , M. Mainard6 , M. Bourliere ` 7 , V. de Ledinghen8 , A. Abergel9 , K. Barange10 , N. Ganne11 , P. Cales12 , V. Di Martino13 , O. Goria14 , J.-M. Molina15 , L. Alric10 , J.-J. Raabe16 . 1 CHU de Nancy, Vandoeuvrel`es-Nancy, 2 CHU de Lille, Lille, 3 CHU de Nice, Nice, 4 CHU de Grenoble, Grenoble, 5 Hopital Cochin, Paris, 6 CHU de Lyon, Lyon, 7 Hopital Saint Joseph, Marseille, 8 CHU de Bordeaux – Hˆ opital Pellegrin, Bordeaux, 9 CHU de Clermont Ferrand, Clermont Ferrand, 10 CHU de Toulouse, Toulouse, 11 Hopital Jean Verdier, Bondy, 12 CHU Angers, Angers, 13 CHU 14 de Besancon, ¸ Besancon, ¸ CHU de Rouen, Rouen, 15 Hopital Saint-Louis, Paris, 16 CHR Metz, Metz, France E-mail: [email protected] Background and Aim: Treatment with PEG-interferon (PEG-IFN) for chronic hepatitis C (CHC) is associated with depression. The aim of the study was to determine the efficacy of paroxetine for preventing depression induced by PEG-IFN in CHC patients. Methods: We designed a prospective, multicenter, double-blind, placebo-controlled trial of the antidepressant paroxetine in CHC adult patients who were eligible for therapy with PEG-IFN-alpha 2a or 2b and ribavirin [NCT00196664]. Patients with symptomatic mental disorders at baseline were excluded, as well as those with HBV or HIV coinfection. The study was conducted in 17 French hospitals. Patients were randomly assigned to receive paroxetine (20 mg/day, n = 73) or placebo (n = 76). Stratification was done on: PEG-IFN (2a vs 2b), history of previous antiviral treatment (no vs yes), HCV genotype (1/4/5 vs 2/3). Treatment was begun 2 weeks before PEG-IFN and continued until 2 weeks after the end of the antiviral therapy. Patients were evaluated every month until the end of PEG-IFN. Main variables were the presence of a major depression evaluated by the Mini International Neuropsychiatric Interview (MINI) and a Montgomery-Asberg Depression Rating Scale (MADRS) >15. We hypothesized a 20 % decrease of depression incidence with paroxetine. Chi-square test and Student’s T test were used for categorical and continuous variables respectively. S104
Results: The characteristics of the 159 included patients were as follow: male: 58 %, age: 50 years, history of psychiatric disorders: 30 %, history of drug use: 32 %, METAVIR F3–F4: 48 %, genotype 1/4/5: 58 %. 64 % patients were naïve of treatment and 52 % received PEGIFN 2a. The 2 arms were well matched. The incidence of depression was not statistically different between the 2 arms according to the MINI (paroxetine: 4 % vs 11 %) and the MADRS (paroxetine: 18 vs 28 %). There was no difference in terms of antiviral dose reduction (34% vs 36 %) and serious adverse events (22% vs 14%). The SVR rates were also comparable (46 vs 54 %). Conclusion: Our results do not support the systematic use of paroxetine in the prevention of the depression induced by PEGIFN in the treatment of CHC. 247 PREDICTING TREATMENT OUTCOME AMONG SLOW RESPONDERS: A RETROSPECTIVE ANALYSIS OF THE SUCCESS STUDY M. Buti1 , V.G. Morozov2 , V.V. Rafalskiy3 , F. Wong4 , J. Sumskiene5 , X. Yu6 , R. Faruqi6 , L.D. Pedicone6 , R. Esteban7 . 1 Dept. of Internal Medicine – Hepatology, Liver Unit Hospital General Universitario Valle Hebron and Ciber-ehd del Instituto Carlos III, Barcelona, Spain; 2 Hepatolog Medical Center, Samara, 3 Smolensk State Medical Academy, Smolensk, Russia; 4 Toronto General Hospital, Toronto, ON, Canada; 5 Clinic of Gastroenterology, Kaunas, Lithuania; 6 Schering Corp., a Division of Merck & Co., Kenilworth, NJ, USA; 7 Liver Unit Hospital General Universitario Valle Hebron and Ciber-ehd del Instituto Carlos III, Barcelona, Spain E-mail: [email protected] Background: Several studies have examined a 72-week (wk) treatment duration with peginterferon plus ribavirin for patients with chronic hepatitis C (CHC) genotype 1 infection; however, there is no consensus regarding the subgroup of patients for which extended treatment should be considered. Aim: To identify on-treatment predictors of sustained virologic response (SVR) in slow responders (≥2log decline in HCV RNA yet detectable at wk 12 and undetectable at wk 24) treated for 48 or 72 wks. Method: This was an open-label, randomized, international study of patients with CHC genotype 1. Slow responders were randomized to receive peginterferon alfa-2b (1.5 mg/kg/wk) plus ribavirin (800– 1400 mg/d) for 48 or 72 wks. Results: 1,428 patients were enrolled of which 159 slow responders were randomized to 48 (n = 86) or 72 wks treatment (n = 73). SVR rates were 43.0% and 47.9% in 48 wk and 72 wk arms. Mean absolute HCV RNA levels at wk 4, 8, and 12 were similar in both arms. Change in HCV RNA at wk 4 was not predictive of SVR (Table). Among slow responders with <2log decline at wk 8, SVR rates were 18.8% and 38.5% in 48 wk and 72 wk arms. Extended treatment did not improve SVR among slow responders with ≥2log decline at wk 8 or with ≥3log decline at wk 12; however, SVR was 25.0% and 46.7% in slow responders with 2–3log decline at week 12 when treated for 48 or 72 wks. Logistic regression revealed a weak association between week 8 viral load (≤2 versus >2log decline) and SVR (odds ratio = 2.504; 95% CI, 0.948 to 6.613; P = 0.064). Conclusion: Slow responders with <2log decline from baseline at wk 8, 2–3log decline at wk 12 and undetectable HCV RNA at wk 24 represent a group of patients who could benefit most from extended treatment. Table. SVR by decline in HCV RNA from baseline Week 4
48 wk arm 72 wk arm
Week 8
Week 12
<2 log
≥2 log
<2 log
≥2 log
2–3 log
3–4 log
≥4 log
27/66 (40.9) 29/58 (50.0)
9/19 (47.4) 6/13 (46.2)
3/16 (18.8) 5/13 (38.5)
33/69 (47.8) 29/57 (50.9)
4/16 (25.0) 7/15 (46.7)
17/38 (44.8) 11/28 (39.3)
16/32 (50.0) 17/30 (56.7)
Journal of Hepatology 2010 vol. 52 | S59–S182
Results: The characteristics of the 159 included patients were as follow: male: 58 %, age: 50 years, history of psychiatric disorders: 30 %, history of drug use: 32 %, METAVIR F3–F4: 48 %, genotype 1/4/5: 58 %. 64 % patients were naïve of treatment and 52 % received PEGIFN 2a. The 2 arms were well matched. The incidence of depression was not statistically different between the 2 arms according to the MINI (paroxetine: 4 % vs 11 %) and the MADRS (paroxetine: 18 vs 28 %). There was no difference in terms of antiviral dose reduction (34% vs 36 %) and serious adverse events (22% vs 14%). The SVR rates were also comparable (46 vs 54 %). Conclusion: Our results do not support the systematic use of paroxetine in the prevention of the depression induced by PEGIFN in the treatment of CHC. 247 PREDICTING TREATMENT OUTCOME AMONG SLOW RESPONDERS: A RETROSPECTIVE ANALYSIS OF THE SUCCESS STUDY M. Buti1 , V.G. Morozov2 , V.V. Rafalskiy3 , F. Wong4 , J. Sumskiene5 , X. Yu6 , R. Faruqi6 , L.D. Pedicone6 , R. Esteban7 . 1 Dept. of Internal Medicine – Hepatology, Liver Unit Hospital General Universitario Valle Hebron and Ciber-ehd del Instituto Carlos III, Barcelona, Spain; 2 Hepatolog Medical Center, Samara, 3 Smolensk State Medical Academy, Smolensk, Russia; 4 Toronto General Hospital, Toronto, ON, Canada; 5 Clinic of Gastroenterology, Kaunas, Lithuania; 6 Schering Corp., a Division of Merck & Co., Kenilworth, NJ, USA; 7 Liver Unit Hospital General Universitario Valle Hebron and Ciber-ehd del Instituto Carlos III, Barcelona, Spain E-mail: [email protected] Background: Several studies have examined a 72-week (wk) treatment duration with peginterferon plus ribavirin for patients with chronic hepatitis C (CHC) genotype 1 infection; however, there is no consensus regarding the subgroup of patients for which extended treatment should be considered. Aim: To identify on-treatment predictors of sustained virologic response (SVR) in slow responders (≥2log decline in HCV RNA yet detectable at wk 12 and undetectable at wk 24) treated for 48 or 72 wks. Method: This was an open-label, randomized, international study of patients with CHC genotype 1. Slow responders were randomized to receive peginterferon alfa-2b (1.5 mg/kg/wk) plus ribavirin (800– 1400 mg/d) for 48 or 72 wks. Results: 1,428 patients were enrolled of which 159 slow responders were randomized to 48 (n = 86) or 72 wks treatment (n = 73). SVR rates were 43.0% and 47.9% in 48 wk and 72 wk arms. Mean absolute HCV RNA levels at wk 4, 8, and 12 were similar in both arms. Change in HCV RNA at wk 4 was not predictive of SVR (Table). Among slow responders with <2log decline at wk 8, SVR rates were 18.8% and 38.5% in 48 wk and 72 wk arms. Extended treatment did not improve SVR among slow responders with ≥2log decline at wk 8 or with ≥3log decline at wk 12; however, SVR was 25.0% and 46.7% in slow responders with 2–3log decline at week 12 when treated for 48 or 72 wks. Logistic regression revealed a weak association between week 8 viral load (≤2 versus >2log decline) and SVR (odds ratio = 2.504; 95% CI, 0.948 to 6.613; P = 0.064). Conclusion: Slow responders with <2log decline from baseline at wk 8, 2–3log decline at wk 12 and undetectable HCV RNA at wk 24 represent a group of patients who could benefit most from extended treatment. Table. SVR by decline in HCV RNA from baseline Week 4
48 wk arm 72 wk arm
Week 8
Week 12
<2 log
≥2 log
<2 log
≥2 log
2–3 log
3–4 log
≥4 log
27/66 (40.9) 29/58 (50.0)
9/19 (47.4) 6/13 (46.2)
3/16 (18.8) 5/13 (38.5)
33/69 (47.8) 29/57 (50.9)
4/16 (25.0) 7/15 (46.7)
17/38 (44.8) 11/28 (39.3)
16/32 (50.0) 17/30 (56.7)
Journal of Hepatology 2010 vol. 52 | S59–S182