Z Gastroenterol 2012; 50 - P4_50
DOI: 10.1055/s-0031-1295936

All-trans retinoic acid co-administered with pegylated interferon and ribavirin does not influence viral kinetics in hepatitis C infected patients with previous non-response: Results of the ATRACTION study

M Schuchmann 1, JM Kittner 1, JF Schlaak 2, D Klaas 3, C Eisenbach 4, T Berg 5, C Trautwein 6, R Günther 7, S Zeuzem 8, R Goesseringer 9, A Ehrlich 10, K Neumann 11, D Wachtlin 10, WO Boecher 12, PR Galle 1
  • 1I. Medizinische Klinik der Universitätsmedizin Mainz, Mainz
  • 2Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen
  • 3Innere Medizin I, Universitätsklinikum Ulm, Ulm
  • 4Innere Medizin IV, Gastroenterologie, Hepatologie, Infektionskrankheiten und Vergiftungen, Universitätsklinikum Heidelberg, Heidelberg
  • 5University of Leipzig, Leipzig
  • 6Medizinische Klinik III, Universitätsklinikum Aachen, Aachen
  • 7Universitätsklinikum Schleswig-Holstein, Klinik für allgemeine Innere Medizin, Kiel
  • 8Medinizische Klinik I, Klinikum der Johann-Wolfgang Goethe-Universität, Frankfurt am Main
  • 9Roche Pharma AG, Grenzach
  • 10Interdisziplinäres Zentrum Klinische Studien, Mainz
  • 11Charite Berlin, Medizinische Biometrie, Berlin
  • 12Boehringer Ingelheim, Biberach

Background: To assess antiviral potential, safety, and tolerability of all-trans retinoic acid (tretinoin) in combination with peg-IFN alfa–2a and ribavirin in HCV–1 infected patients with prior non-response. Viral kinetics in the initial 12 weeks of treatment were used as the primary endpoint. Method: Randomized, open label, multicenter clinical trial. Patients received either pegIFN (P)/ribavirin (R) plus tretinoin in a dosage of 45mg/m2 for 12 weeks followed by PR therapy for 36 weeks (A) or standard therapy (PR) only (B). Therapy-induced viral decay was estimated using a three compartment model (“free viral load”, “productively infected hepatocytes”, and “uninfected hepatocytes”), with differential equations describing “clearance rate of free virions” (c), “antiviral effects in the initial phase” (ε), and “clearance rates of infected hepatocytes” during the second (δ) or third phase (Mδ), respectively. Results: 81 patients received at least one dosage of treatment. Due to major protocol deviations at one trial site, 13 patients had to be excluded, allowing safety analysis in 68 patients (34 in each arm). Adverse events (AE) were more common in arm A with triple combination: gastrointestinal 30 vs. 18 cases, headache 28 vs. 13, and dermatological (dry skin, alopecia) 29 vs. 18. 9 patients in arm A experienced AEs of severe intensity (headache (4) and others), whereas AEs in arm B were all mild or moderate. No SUSAR was observed. Viral kinetic parameters were analyzed in the per protocol population (27 pts. in arm A, 30 pts. in arm B). No significant differences between the study groups were seen for any of the kinetic parameters. In line with this, rates of ≥2 log10 drop at week 12 were similar between arm A (10/27) and arm B (11/30). Conclusion: Addition of tretinoin to PR was safe and acceptably tolerated. However, it did not influence viral kinetics of HCV RNA decline in patients with chronic HCV and former non-response to PR standard therapy.

all-trans retinoic acid - chronic hepatitis C - genotype 1 - non-responder - viral kinetics