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. *firstname.lastname@example.org
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.