Poster Presentations

Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010

IMPACT OF HIGHER DOSES OF PEGINTERFERON ALFA-2A AND RIBAVIRIN ON RVR, CEVR AND SVR IN HCV G1 PATIENTS WITH VIRAL LOADS ≥400 000IU/ML WEIGHING ≥85KG

K.R. Reddy¹*, M.L. Shiffman², M. Rodriguez-Torres³, D. Abdurakhmanov⁴, I. Bakulin⁵, G.F. Silva⁶, H. Cheinquer⁷, M. Rabbia⁸, M. McKenna⁹, A. Tietz¹⁰, S.A. Harrison¹¹, On behalf of the PROGRESS Study Investigators
¹Hospital of the University of Pennsylvania, Philadelphia, PA, ²Bon Secours Health System, Liver Institute of Virginia, Newport News, VA, ³Fundacion de Investigacion De Diego Santurce, Santurce, PR, USA, ⁴Moscow Medical Academy, ⁵State Postgraduate Medical Institute, Ministry of Defence of the Russian Federation, Moscow, Russia, ⁶Botucatu School of Medicine, Botucatu, ⁷Hospital de Clinicas de Porto Alegre, Porte Alegre, Brazil, ⁸Roche, Nutley, NJ, USA, ⁹Roche, Welwyn, UK, ¹⁰Roche, Basel, Switzerland, ¹¹Brooke Army Medical Center, Houston, TX, USA. *rajender.reddy@uphs.upenn.edu

Background: HCV therapy in genotype 1 (G1), higher viral load and higher bodyweight patients is associated with lower SVR rates. The PROGRESS study investigated the efficacy and safety of higher induction doses of peginterferon alfa-2a (40KD) (PEGASYS^®; PegIFNα2a) and/or higher RBV doses in patients with all of these difficult-to-cure characteristics.
Methods: Overall, 1175 G1 patients with a viral load ≥400 000IU/mL and bodyweight ≥85kg were randomised to 48 weeks of PegIFNα2a 180µg/week plus RBV 1200mg/day (Arm-A) or 1400 (bodyweight < 95kg)/1600mg/day (bodyweight ≥95kg) (Arm-B) or to 12 weeks of PegIFNα2a 360µg/week then180µg/week for 36 weeks plus RBV 1200mg/day (Arm-C) or 1400/1600mg/day (Arm-D). The primary efficacy endpoint was undetectable HCV-RNA (< 15IU/mL) after 24 weeks' untreated follow-up (SVR). RVR and cEVR were defined as undetectable HCV-RNA at week 4 and 12, respectively.
Results: Overall SVR rates were similar for all treatments (38-44%) (Table). Across arms, approximately 63-69% of patients received >80% of the scheduled cumulative dose of PegIFNα2a and RBV. Among these patients, rates of SVR were higher overall (50-60%). Patients receiving PegIFNα2a induction dosing tended to have higher rates of RVR (17-18% vs 12% with standard dosing) and cEVR (58-61% vs 53-55%). This trend did not translate into higher SVR rates in Arms C and D, although patients that achieved an RVR or cEVR had consistently high SVR rates (RVR 77-89%; cEVR 61-69%).
Conclusions: In these difficult-to-treat G1 patients with high viral load and body weight, SVR rates were similarly high across the four treatment arms (38-44%); however, in those with good adherence (>80% PegIFNα2a/RBV exposure) SVR rates were excellent overall (50-60%), with a trend to even higher rates with the more intensive regimens (57-60%) relative to the standard of care (50%). An RVR or cEVR was highly predictive of SVR.


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