1885A baseline predictive tool for selecting HBeAg-negative chronic hepatitis B patients who have a high probability of achieving sustained immune control with peginterferon alfa-2a
Pietro Lampertico1, Vivien Rothe2, Antonietta Caputo3, George V. Papatheodoridis4;1AM & A Migliavacca Center for Liver Disease, 1st Gastroenterology Unit, Fondazione IRCCS Ca' Granda Osped-ale Maggiore Policlinico, Universita degli Studi di Milano, Milan, Italy; 2IST GmbH, Mannheim, Germany; 3Roche S.p.A., Monza, Italy; 4Department of Gastroenterology, Athens University Medical School, Laiko General Hospital, Athens, Greece
Objective: Peginterferon (PegIFN) alfa-2a induces serologic responses that are durable after the withdrawal of treatment in patients with HBeAg-negative chronic hepatitis B (CHB). Not all patients achieve a response; thus, the ability to identify patients likely to respond would be clinically useful. We aimed to develop a simple scoring system that can prospectively estimate a patient's chance of achieving sustained immune control (SIC) and sustained response (SR) with PegIFN alfa-2a. Methods: This retrospective analysis used data from HBeAg-negative CHB patients who received PegIFN alfa-2a 180 mg/week ± lamivudine for 48 weeks in 2 large studies. SIC was defined as HBV DNA <2000 IU/mL and SR was defined as HBV DNA <2000 IU/mL plus normal ALT after 48 weeks of untreated follow-up. Logistic regression analyses identified predictors of response, and generalized additive models with logit link identified cut-points for continuous predictors. The baseline scoring system comprised 5 factors; points were assigned as follows: genotype C (+1), HBV DNA <250,000 IU/mL (+1), ALT ≥5 × upper limit of normal (+1), HBsAg: ≥1000 but <3500 IU/ mL (+1), <1000 IU/mL (+2); age: 30–45 years (+1), <30 years (+2). The overall baseline score ranged from 0–7; higher scores indicated a higher chance of SIC and SR. Results: Among patients with data available at Week 48 post-treatment (N=263), 32%, 49%, and 19% of patients had scores of 0-1, 2-3, or ≥4 points, respectively. SR and SIC rates improved as baseline scores increased (Table). At Week 48 post-treatment, SIC and SR rates were 61% and 45%, respectively, in patients with scores ≥4 and 11% (negative predictive value [NPV] 89%) and 8% (NPV 92%) in patients with scores 0-1. The increases in SIC and SR rates with increasing baseline scores were consistent across both studies and independent of lamivudine therapy. Conclusion: The proposed baseline scoring system uses readily available baseline characteristics to identify HBeAg-negative CHB patients who have a low or high chance of achieving SR or SIC with PegIFN alfa-2a. The benefit/risk ratio should be carefully considered before initiating treatment in patients with scores of 0–1, while prediction of response might be further improved by application of established on-treatment prediction rules (e.g., PARC) in patients with scores ≥2. Funded by Roche
Disclosures:
Pietro Lampertico - Advisory Committees or Review Panels: BMS, Roche, Gilead; Speaking and Teaching: BMS, Roche, Gilead, GSK, MSD
Antonietta Caputo - Employment: Roche
George V. Papatheodoridis - Advisory Committees or Review Panels: Merck, Novartis, Abbvie, Boerhinger, Bristol-Meyer Squibb, Gilead, Roche, Janssen, GlaxoSmith Kleine; Grant/Research Support: Roche, Gilead, Bristol-Meyer Squibb, Abbvie, Janssen; Speaking and Teaching: Merck, Bristol-Meyer Squibb, Gilead, Roche, Janssen, Abbvie
The following people have nothing to disclose: Vivien Rothe 作者: StephenW 时间: 2014-10-24 15:08