Crohn’s disease (CD) is a debilitating inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the “inflammatory reflex”, has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD in a 16-week open-label multicentre clinical trial.

A vagus nerve stimulator was implanted in 17 biological drug-refractory patients with moderately-to-severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation (4/16 receiving concomitant biologics) during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient reported outcomes, objective measures of inflammation (endoscopic/molecular), and safety.

There was a statistically significant and clinically meaningful decrease in CD Activity Index at Week-16 (mean±SD:-86.2±92.8, p=0.003), a significant decrease in faecal calprotectin (-2923±4104, p=0.015), a decrease in mucosal inflammation in 11/15 patients with paired endoscopies (-2.1±1.7, p=0.23), and a decrease in serum TNF and IFN-γ (46-52%). Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related SAE: a post-operative infection requiring device explantation.

Neuroimmune modulation via vagus nerve stimulation was generally safe and well-tolerated with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality-of-life.