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Meta-Analysis
. 2021 Oct;54(7):880-889.
doi: 10.1111/apt.16583. Epub 2021 Aug 25.

Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH

Abdul M Majzoub  1 , Tarek Nayfeh  2 , Abbey Barnard  3 , Nagambika Munaganuru  3 , Shravan Dave  3 , Siddharth Singh  3 , Mohammad Hassan Murad  2 , Rohit Loomba  3
Affiliations
Meta-Analysis

Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH

Abdul M Majzoub et al. Aliment Pharmacol Ther. 2021 Oct.

Abstract

Background: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for the treatment of NASH.

Aim: To assess the relative rank-order of different pharmacological interventions in fibrosis improvement and NASH resolution.

Methods: A comprehensive search of several databases was conducted by an experienced librarian. We included randomised controlled-trials (RCTs) comparing pharmacological interventions in patients with biopsy-proven NASH. The primary outcome was ≥1 stage improvement in fibrosis. The secondary outcome was NASH resolution.

Results: A total of 26 RCTs with 23 interventions met the eligibility criteria. Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively. For NASH resolution, semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively. Lanifibranor, obeticholic acid, pioglitazone and vitamin E were significantly better than placebo in achieving ≥1 stage of fibrosis improvement. Conversely, semaglutide, liraglutide, vitamine E plus pioglitazone, pioglitazone, lanifibranor and obeticholic acid were significantly better than placebo in achieving NASH resolution.

Conclusion: These data provide relative rank-order efficacy of various NASH therapies in terms of their improvements in liver fibrosis and NASH resolution. Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.

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Conflict of interest statement

Conflict of interests: Dr. Rohit Loomba serves as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myer Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse bio, GNI, GRI Bio, Intercept, Ionis, Janssen Inc., Merck, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens. He is also co-founder of Liponexus, Inc.

Figures

Figure 1.
Figure 1.
Network of the included studies with the available direct comparisons for the primary outcome. The size of the nodes and the thickness of the edges are weighted according to the number of patients and the number of studies evaluating each treatment, respectively.
Figure 2.
Figure 2.
Meta-analysis forest plots of different pharmacological interventions compared to placebo for the primary outcome
Figure 3.
Figure 3.
Network meta-analysis forest plot of different pharmacological interventions compared to placebo ranking from best to worst based on SUCRA score for the primary outcome
Figure 4.
Figure 4.
Network of the included studies with the available direct comparisons for the secondary outcome. The size of the nodes and the thickness of the edges are weighted according to the number of patients and the number of studies evaluating each treatment, respectively.
Figure 5.
Figure 5.
Meta-analysis forest plots of different pharmacological interventions compared to placebo for the secondary outcome.
Figure 6.
Figure 6.
Network meta-analysis forest plot of different pharmacological interventions compared to placebo ranking from best to worst based on SUCRA score for the secondary outcome.
Figure 7.
Figure 7.
SUCRAs for NASH resolution and at least 1 stage fibrosis improvement.
See this image and copyright information in PMC

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