Vagus nerve stimulation in Crohn’s disease: long-term outcomes, mechanistic insights, and the promise of non-invasive approaches

The vagus nerve (VN) has anti-inflammatory properties. We have previously reported in a 1-year pilot study that VN stimulation (VNS) improved patients with active Crohn’s disease (CD). In this paper, we present the results of the long-term follow-up of these CD patients (between four and ten years) and raise questions about the use of VNS in inflammatory bowel disease. At the end of the pilot study, the 7 patients who ended the pilot study (corresponding to a 1-year active VNS), accepted to continue VNS as well as the 2 patients retrieved from the study, because of an early worsening (at 3 months of VNS) of their disease. Patients were then followed-up twice a year as far as possible with clinical and biological evaluation. Ileo-colonoscopy, as well as intestinal ultrasound evaluation were performed as far as possible. Vagal tone was evaluated by heart rate variability (HRV). The state perceived digestive pain score and the anxiety and depression score were also evaluated. Over a decade-long follow-up of nine CD patients implanted with VNS, sustained clinical benefits were observed despite heterogeneous disease courses and treatment histories. Three patients achieved long-term remission under VNS alone, without any additional therapy at 10 years. Several others initially controlled disease activity with VNS alone for 3–7 years before required biologics or surgery, most often during COVID-19. Clinical, biological, and endoscopic markers generally improved or stabilized, with relapse episodes responding to added standard therapies when needed. Autonomic data showed increased median parasympathetic HRV (HFnu) after implantation, persisting over six years despite interindividual variability. Median anxiety–depression scores decreased below clinical thresholds, and digestive pain shifted from moderate to low within the first year and remained low thereafter. Overall, long-term VNS was feasible, well tolerated, and associated with durable symptom control or remission in this small pilot cohort. This pilot study should primarily be viewed as a proof-of-concept demonstration that long-term invasive cervical VNS is feasible, safe, and acceptable for CD patients. It also highlights a potential therapeutic signal in a subset of individuals, supporting further investigation.