Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges

• Published in: Gut Vol. 69; no. 10; pp. 1877 - 1884
• Main Authors: Dufour, Jean-François, Caussy, Cyrielle, Loomba, Rohit
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.10.2020; BMJ Publishing Group
• Subjects: Bile; Cholesterol; Cirrhosis; Clinical trials; Clinical Trials as Topic; Combination therapy; Diabetes; Drug dosages; Drug Therapy, Combination - methods; Fatty acids; FDA approval; Glucose; Histology; Humans; Inflammation; Insulin; Life Sciences; Liver; Liver cirrhosis; Low density lipoprotein; Medication Therapy Management - trends; Metabolism; Non-alcoholic Fatty Liver Disease - drug therapy; Recent Advances in Clinical Practice; Regulatory approval; Treatment Outcome; nonalcoholic steatohepatitis; liver; hepatobiliary disease; institution has received grant support from Allergan; Celgene; Prometheus; Glympse bio; Genfit; Eli Lilly and Company; Novartis. RL serves; pH Pharma; his; Conatus; Siemens; Madrigal; AstraZeneca; Sanofi; Gilead. J-FD Advisory committees: Bayer; and Viking Therapeutics. In addition; Bristol-Myers Squibb; as a consultant or advisory board member for Arrowhead Pharmaceuticals; Bird Rock Bio; Galectin Therapeutics; Ionis; NuSirt; Gilead Science; Gemphire; CohBar; Boehringer Ingelheim; Falk; NGM Biopharmaceuticals; and Siemens. He is also cofounder of Liponexus; GNI; Genkyotex; Grail; Intercept; Eli Lilly; Science; Cirius; Merck; Bristol-Myer Squibb; Speaking and teaching; Janssen; GRI Bio; GE; Metacrine; BristolMyers Squibb; Pfizer; Bayer; BMS; Galmed; Novartis; Boehringer-Ingelheim; Novo Nordisk; Gilead; Pharmaceuticals; HepaRegenix
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2019-319104

Non-alcoholic steatohepatitis (NASH) is becoming a leading cause of cirrhosis with the burden of NASH-related complications projected to increase massively over the coming years. Several molecules with different mechanisms of action are currently in development to treat NASH, although reported efficacy to date has been limited. Given the complexity of the pathophysiology of NASH, it will take the engagement of several targets and pathways to improve the results of pharmacological intervention, which provides a rationale for combination therapies in the treatment of NASH. As the field is moving towards combination therapy, this article reviews the rationale for such combination therapies to treat NASH based on the current therapeutic landscape as well as the advantages and limitations of this approach.