Adverse events occur in two-thirds of NASH patients on placebo

Nearly two in three participants in the placebo arm of nonalcoholic steatohepatitis (NASH) randomized clinical trials (RCTs) experience an adverse event (AE), while one in 10 have a serious AE, according to a pooled analysis of studies with NASH placebo.

A team of investigators searched the databases of Medline, Embase, and Cochrane Central Register of Controlled trials for phase II to IV NASH RCTs with placebo treatment arms. They used a generalized linear mixed model with Clopper-Pearson intervals to analyse a pooled proportion of AEs.

The meta-analysis included 41 RCTs, with a total of 2,944 participants on placebo. Pooled results showed that 68 percent (95 percent confidence interval [CI], 55‒77) of patients in the placebo arm experienced an AE, 7.8 percent (95 percent CI, 5.7‒10) had serious AEs, and 3.1 percent (95 percent CI, 1.9‒5.1) had AEs that led to treatment cessation.

More participants in phase III studies experienced serious AEs compared to phase II studies (p<0.01) and in pharmaceutical-funded studies than federal-funded ones (p<0.01). In addition, 10 percent (95 percent CI, 5.5‒18) of participants on placebo developed pruritus on analysis of RCTs evaluating bile acid modulating agents.

“In the absence of an effective treatment for NASH, RCT remains the current gold standard study design in NASH,” the investigators said.

“As NASH is a largely asymptomatic disease, the side effects of potential therapies require careful evaluation, therefore a pooled rate of the AEs in placebo-treated patients serves as a useful comparator for safety,” they added.