58 - Efficacy and Safety of Rifaximin Treatment for Reducing the Risk of Overt Hepatic Encephalopathy by Baseline Hepatic Impairment
Wednesday, October 10
9:00 AM - 9:10 AM
Location: Terrace Ballroom 4 (level 400)
Steven L. Flamm, MD1, Jasmohan S. Bajaj, MD2, Zeev Heimanson, PharmD3, Guy Neff, MD4
1Northwestern Feinberg School of Medicine, Chicago, IL; 2Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA; 3Salix Pharmaceuticals, Bridgewater, NJ; 4Florida Research Institute, Florida Digestive Health Specialists, Lakewood Ranch, FL
Steven Flamm, MD
Professor of Medicine and Surgery
Northwestern Feinberg School of Medicine
Introduction: Rifaximin is indicated for reducing the risk of overt hepatic encephalopathy (OHE) recurrence in adults. This analysis, in a population with cirrhosis, evaluated rifaximin for reducing the risk of OHE recurrence, assessed by patient baseline hepatic impairment.
Methods: In a randomized, double-blind trial, adults with cirrhosis with a history of ≥2 OHE episodes during the previous 6 months, currently in HE remission (Conn score ≤1), received rifaximin 550 mg twice daily (BID) or placebo for up to 6 months.1 This post hoc analysis evaluated time to first breakthough OHE episode in patients stratified by baseline Child-Pugh class (A, B, or C). Breakthrough OHE was defined as an increase in Conn score to ≥2 or an increase in both Conn score and asterixis score of 1 grade each for patients entering with a Conn score of 0.
Results: Overall, 140 (rifaximin) and 159 (placebo) patients were treated; mean age was 55.5 vs 56.8 y; 53.6% vs 67.3% of patients were male; 91.4% vs 91.2% used concomitant lactulose; and 46 vs 56 patients were classified as Child-Pugh class A at baseline, 65 vs 72 patients as class B, and 17 vs 14 patients as class C. There were no notable differences between rifaximin and placebo groups in mean number of days of treatment across baseline Child-Pugh classes. OHE breakthrough episodes were reported in 17.4% of patients in rifaximin group vs 46.4% in placebo group for Child-Pugh class A, 23.1% vs 44.4% for class B, and 29.4% vs 64.3% for class C. Treatment with rifaximin resulted in 66%, 56%, and 66% reduction in risk of breakthrough OHE vs placebo for Child-Pugh class A, B, and C, respectively: class A, hazards ratio (HR), 0.34 (95% CI, 0.15, 0.75; P=0.005); class B, HR, 0.44 (95% CI, 0.24, 0.82; P=0.007); and class C, HR, 0.34 (95% CI, 0.12, 1.04; P=0.047). Incidence of serious adverse events (SAEs) was generally similar in rifaximin vs placebo groups across classes: class A (28.3% vs 41.1%), class B (38.5% vs 36.1%), and class C (47.1% vs 50.0%). There were no apparent trends in between-group differences (rifaximin vs placebo) in types and frequencies of SAEs in each class.
Discussion: Regardless of Child-Pugh class of hepatic impairment, treatment with rifaximin 550 mg BID (plus lactulose [~91% of patients]) significantly reduced the risk of OHE recurrence (up to 66% vs placebo [lactulose alone; ~91%]) and was safe and well tolerated in patients with cirrhosis.
1. Bass NM, et al. N Engl J Med. 2010;362(12):1071-1081.
Steven Flamm: AbbVie – Advisory Committee/Board Member, Consultant. Bristol-Myers Squibb Company – Advisory Committee/Board Member, Consultant. Gilead Sciences, Inc. – Advisory Committee/Board Member, Consultant. Intercept Pharmaceuticals, Inc. – Advisory Committee/Board Member, Consultant. Merck & Co., Inc. – Advisory Committee/Board Member, Consultant. Salix Pharmaceuticals, Inc. – Advisory Committee/Board Member, Consultant.
Jasmohan Bajaj: Salix Pharmaceuticals, Inc. – Advisory Committee/Board Member.
Zeev Heimanson: Salix Pharmaceuticals, Inc. – Employee.
Guy Neff indicated no relevant financial relationships.