Placebo Adverse Events in Non-alcoholic Steatohepatitis Clinical Trials: A Pooled Analysis of 2,944 Participants
Year: 2022
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: INTRODUCTION: In the absence of an effective treatment for non-alcoholic steatohepatitis (NASH), a randomized, placebo-controlled trial (RCT) remains the current gold standard study design in NASH. As NASH is a largely asymptomatic disease, the side effects of potential therapies require careful evaluation, therefore a pooled rate of the adverse events (AEs) in placebo-treated patients serves as a useful comparator for safety. Therefore, we performed a systematic review and meta-analysis to estimate the rate of AEs among participants in the placebo arm of NASH RCTs. METHODS: Medline, Embase and Cochrane Central Register of Controlled Trials were searched to include clinical trials in phase 2-4 NASH RCTs with placebo treatment arms. A pooled proportions of AEs were analyzed using a generalized linear mixed model with Clopper-Pearson intervals. RESULTS: A total of 41 RCTs (2,944 participants on placebo) were included in this meta-analysis. A total of 68% (confidence interval [CI] 55%-77%) of participants on placebo experienced an AE, 7.8% (5.7%-10%) experienced serious AEs and 3.1% (CI: 1.9%-5.1%) experienced AEs leading to discontinuation. A significantly higher proportion of participants experienced serious AEs in phase 3 studies compared to in phase 2 studies ( P < 0.01) and in pharmaceutical funded studies as compared to studies which were federal-funded studies ( P < 0.01). An analysis of clinical trials evaluating bile acid modulating agents determined that 10% (CI: 5.5%-18%) of participants receiving placebo developed pruritus. DISCUSSION: The present study summarizes the AEs with NASH placebo. Among participants in the placebo arm in NASH, two-third experienced an AE, and nearly 10% experienced a serious AE.
Authors: Phoebe Wen Lin Tay, Cheng Han Ng, Snow Yunni Lin, Yip Han Chin, Jieling Xiao, Wen Hui Lim, Sze Yinn Lim, Clarissa Elysia Fu, Kai En Chan, Jingxuan Quek, Darren Jun Hao Tan, Nicholas Chew, Nicholas Syn, Taisei Keitoku, Nobuharu Tamaki, Mohammad Shadab Siddiqui, Mazen Noureddin, Mark Muthiah, Daniel Q. Huang, Rohit Loomba
Institutions: National University of Singapore, National University Heart Centre Singapore, National University Hospital, National University Health System, Musashino Red Cross Hospital, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, Cedars-Sinai Medical Center, University of California San Diego
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Institutes of Health, Medical Research Council, National Medical Research Council, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1140353899, A Cardiovascular-NASH disease nexus: Common Mechanisms and Treatments?, Non-invasive screening of diabetics for advanced fibrosis due to NAFLD, Novel IL-23 inhibitor for the treatment of alcohol associated liver disease, Ancillary Studies of NAFLD and NASH in HIV infected Adults, QUS Technology for Diagnosis and Grading of Hepatic Steatosis in NAFLD, UC San Diego Clinical and Translational Research Institute, San Diego Digestive Diseases Research Center, Clinical Research on Nonalcoholic Fatty Liver Disease, San Diego Cirrhosis Clinical Research Network
OpenAlex ID: W4300817262