World Congress at ACG2017

Simultaneous Plenary Session 4A: Liver

58 - Assessment of Potential Impact of Demographic and Baseline Disease Characteristics on Rifaximin Monotherapy versus Lactulose Combination Therapy for the Prevention of Overt Hepatic Encephalopathy (OHE) Recurrence

Wednesday, October 18
9:20 AM - 9:30 AM
Location: Valencia Ballroom BC (Level 4)



Category: Liver       

Steven Flamm, MD1, Kevin Mullen, MD2, Zeev Heimanson, PharmD3, Arun Sanyal, MD4
1Northwestern University Feinberg School of Medicine, Chicago, IL; 2MetroHealth Medical Center, Cleveland, OH; 3Salix Pharmaceuticals, Bridgewater, NJ; 4Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA
Introduction: Rifaximin 550 mg is indicated for prevention of OHE recurrence in adults. A phase 4, open-label noninferiority trial evaluated the impact of baseline parameters on the efficacy of rifaximin alone vs rifaximin + lactulose for OHE recurrence prevention.

Methods: Adults with cirrhosis and a previous OHE episode now in remission (Conn score ≤1) were randomized to rifaximin 550 mg BID alone or rifaximin 550 mg BID + lactulose (self-titrated; 2-3 soft stools/d) for 6 months. Breakthrough HE (Conn score ≥2) was monitored monthly. Time to onset of an OHE episode (primary endpoint) was assessed overall and by baseline parameters: age ( < 65 y; ≥65 y), sex, race, prior lactulose use, diabetes status, MELD score, Conn score (0; 1), Child-Pugh class, asterixis grade (0; ≥1), duration of HE remission before study entry (≤90 days; >90 days), time since first diagnosis of advanced liver disease ( < 50 months; 50 months), time since first diagnosis of HE ( < 15 months; ≥15 months), number of HE episodes during past 6 months (1; >1), and cirrhosis etiology. Noninferiority was demonstrated if the upper limit 2-sided, 95% CI of hazard ratio (HR) of rifaximin to rifaximin + lactulose was < 1.6.

Results: 113 patients were treated in the rifaximin alone group; 108 in rifaximin + lactulose group. Overall population mean MELD score was 11.9, 39.8% and 55.7% were Child-Pugh A and B, respectively, and baseline parameters were similar between groups. Breakthrough HE was reported in fewer patients in rifaximin + lactulose (13.9%) vs rifaximin alone (24.8%) groups; rifaximin + lactulose reduced the risk of breakthrough HE over 6 months to a greater degree (rifaximin alone vs combination HR, 2.0; 95% CI, 1.0-3.7; P=0.04). Demographic and baseline characteristics evaluated did not substantially alter the risk profile with rifaximin alone vs rifaximin + lactulose. In some subgroups (ie, Child-Pugh A [HR, 0.7; 95% CI, 0.2-2.4; P=0.6], remission duration >90 days [HR, 0.9; 95% CI, 0.4-2.1; P=0.7], prior 6-month HE episodes >1 [HR, 0.9; 95% CI, 0.3-2.7; P=0.9]), rifaximin alone reduced the risk of breakthrough HE to a greater degree than rifaximin + lactulose (ie, HR < 1); however, differences were not significant.

Discussion: Rifaximin + lactulose therapy appears to be consistently efficacious in prevention of OHE recurrence vs rifaximin alone and was unaltered by baseline characteristics evaluated. These data support the generalizability of the primary endpoint results.

Supported by Industry Grant: Yes

Disclosures: Does Disclose

Steven Flamm: AbbVie, Bristol-Myers Squibb, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., and Salix Pharmaceuticals – Advisory Committee/Board Member, Consultant. AbbVie, Gilead Sciences, Inc., and Intercept Pharmaceuticals, Inc. – Grant/Research Support.
Kevin Mullen: Norgine and Salix Pharmaceuticals – Consultant.
Zeev Heimanson: Salix Pharmaceuticals – Employee.
Arun Sanyal: AbbVie, AstraZeneca, Bristol-Myers Squibb, Durect Corp., Eli Lilly and Company – Consultant. AstraZeneca, Bristol-Myers Squibb, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., and Merck & Co., Inc. – Grant/Research Support. Enanta Pharmaceuticals, Inc., Galmed Pharmaceuticals Ltd., Genfit, Gilead Sciences, Inc., Ikaria – Consultant. Genfit – Stockholder/Ownership Interest (excluding diversified mutual funds). Immuron, Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Nitto Denko Corp., Novartis, Salix Pharmaceuticals, and Zafgen – Consultant. Sanyal Biotechnology – Employee.

Citation: . ASSESSMENT OF POTENTIAL IMPACT OF DEMOGRAPHIC AND BASELINE DISEASE CHARACTERISTICS ON RIFAXIMIN MONOTHERAPY VERSUS LACTULOSE COMBINATION THERAPY FOR THE PREVENTION OF OVERT HEPATIC ENCEPHALOPATHY (OHE) RECURRENCE. Program No. 58. World Congress of Gastroenterology at ACG2017 Meeting Abstracts. Orlando, FL: American College of Gastroenterology.

Steven Flamm

Professor of Medicine and Surgery
Northwestern Feinberg School of Medicine
Chicago, IL

Steven L. Flamm, MD is a Professor of Medicine and Surgery with the Division of Hepatology at Northwestern University Feinberg School of Medicine in Chicago, Illinois. He also serves as the Medical Director of Liver Transplantation. Dr. Flamm received his MD degree from the University of Pennsylvania School of Medicine. He completed both a clinical fellowship in gastroenterology and a research fellowship in gastroenterology and hepatology at Beth Israel Hospital, Harvard Medical School. He then went on for further specialized training, completing a clinical fellowship in hepatology and liver transplantation at The Deaconess Hospital, Harvard Medical School. Dr. Flamm is a member of the American Gastroenterological Association (AGA) and the American Association for the Study of Liver Diseases (AASLD). He has served as the Region 7 Representative to the UNOS Liver and Intestine Committee and on the Publication and Practice Guidelines Committees of the AALSD. Dr. Flamm has published widely in the field of hepatic diseases and has spoken both nationally and internationally on many other liver-related topics including viral hepatitis, autoimmune hepatitis, hepatic encephalopathy, and liver transplantation. He has an active clinical research program in chronic viral hepatitis (HBV and HCV) and autoimmune hepatitis.

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58 - Assessment of Potential Impact of Demographic and Baseline Disease Characteristics on Rifaximin Monotherapy versus Lactulose Combination Therapy for the Prevention of Overt Hepatic Encephalopathy (OHE) Recurrence



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