Efficacy of high-dose ACTH versus low-dose ACTH in infantile spasms: A meta-analysis with direct and indirect comparison of randomized trials

To determine the influence of dose on the efficacy and safety of adrenocorticotropic hormone (ACTH) for infantile spasms. We searched six relative databases. Randomized controlled trials and crossover studies, which meet our inclusion criteria were considered for inclusion. The quality of included trials was evaluated with respect to sequence generation, allocation concealment, blinding and incomplete data. We performed both direct and indirect meta-analysis to evaluate the efficacy and safety of high-dose and low-dose of ACTH. Results: A total of 168 reports were retrieved, and after scrutiny seven reports of trials containing three head to head comparisons, two vigabatrin comparisons and two prednisone comparisons were included. In direct comparison meta-analysis, studies were homogenous (P > 0.10). There was a trend towards more complete cessation of spasms in the low-dose ACTH treated group (RR: 0.86, 95% confidence interval [CI]: 0.57-1.31), though statistically not significant. Relapse was more frequent in low-dose ACTH groups (RR: 0.69, 95% CI: 0.22-2.19) but without demonstrating statistic difference. No difference was present for disappearance of hypsarrhythmia between high and low-dose ACTH (RR: 0.93, 95% CI: 0.57-1.54). In indirect meta-analysis the comparison of complete cessation of spasms between high-dose and low-dose ACTH from indirect meta failed to show any significant difference. There was no significant difference between two dosages with respect to relapse rates. High-dose ACTH produced more adverse effects than low-dose group. A low-dose ACTH therapy might be preferable for its comparative efficacy and lower risk of adverse effects.