Konstantinos C Fragkos

Irritable bowel syndrome with diarrhea (IBS-D) has limited options for treatment currently, including mainly anti-motility medications, antispasmodics, and antidepressants. This review discusses the properties of a new drug, eluxadoline, a gut-targeting mu- and kappa-opioid receptor agonist and a delta-opioid receptor antagonist, and its efficacy and safety in patients with IBS-D. A systematic review of the literature was undertaken to identify studies that had investigated eluxadoline as a treatment in IBS-D. A narrative review of other information is provided with respect to pharmacological and chemical properties. Where suitable, meta-analysis was performed with a random-effects model to produce a pooled estimate. Eluxadoline showed efficacy improving stool consistency (standardized mean difference [SMD]: -0.29 at 12 weeks, p = 0.0004; -0.46 at 26 weeks, p = 0.0001), global symptoms (SMD: -0.15 at 12 weeks, p = 0.006; -0.14 at 26 weeks, p = 0.02), quality of life (SMD: 0.21 at 12 weeks, p < 0.0001; 0.16 at 26 weeks, p = 0.007), pain (SMD: -0.17 at 12 weeks, p = 0.001; -0.16 at 26 weeks, p = 0.01), and adequate relief (odds ratio [OR]: 1.99 at 12 weeks, p < 0.00001; 1.78 at 26 weeks, p < 0.0001). It also improved IBS severity and other abdominal symptoms such as bloating, discomfort, and risk of urgency and fecal incontinence. Its main side effects included constipation (OR: 3.49, p < 0.00001), vomiting (OR: 3.42, p = 0.0002), abdominal pain (OR: 1.78, p = 0.007), and nausea (OR: 1.42, p = 0.07). The overall quality of trials was satisfactory with the meta-analyses providing largely homogeneous outcomes. Eluxadoline's place in clinical practice might prove useful since the pharmacological options of IBS-D are limited and eluxadoline showed a positive effect in treating the symptoms of IBS-D.