Meta-Analysis: Efficacy and Safety of Sequestrants for Bile Acid Diarrhoea

Bile acid diarrhoea, a common cause of diarrhoea-predominant irritable bowel syndrome, has a similar prevalence to coeliac disease and inflammatory bowel diseases. The mainstay of treatment is bile acid sequestrants (BAS). The effectiveness of using bile acid-targeted therapies remains unclear.

To compare BAS with placebo for bile acid diarrhoea.

We conducted a systematic review and meta-analysis of randomised controlled trials comparing BAS to placebo using a comprehensive search of databases from inception to 8/1/2023. Inclusion required unequivocal diagnosis using serum or faecal biochemical parameters, or ⁷⁵SeHCAT. Co-primary endpoints were ≥ 30% improvement in bowel movement consistency and frequency averaged over 7 days. Adverse effects were also summarised.

Database search resulted in 1152 citations; 1 additional study was added. Ultimately, 6 trials (5 parallel arm, 1 crossover) involving 182 participants evaluated the effectiveness of BAS over 1-8 weeks. Participants were between the third and seventh decades of life and mostly female. The risk of bias was low except in one parallel and one crossover trial. Meta-analysis of parallel-design trials of sequestrants only showed a clinically significant reduction in stool consistency and frequency with pooled relative risks of 1.50 (95% CI: 1.14-1.96) and 2.80 (95% CI: 1.68-4.67), respectively. There was no observable heterogeneity (I² = 0%), and the certainty of evidence was moderate. There was no statistically significant difference in adverse effects.

This study quantifies the significant and rapid improvement in both stool consistency and frequency with BAS in patients with objective diagnosis of bile acid diarrhoea. Sequestrants also appear well tolerated.