Su1381 Vagus Nerve Stimulation in Active Crohn's Disease

Aim: The vagus nerve (VN) has an anti-inflammatory role through the cholinergic antiinflammatory pathway (Mol Med 2003;9:125-34). VN stimulation (VNS) improves colitis in rats (Auton Neurosci 2011;160:82-9) but has never been used in the treatment of Crohn's disease (CD).We performed a pilot study of VNS in patients with active CD (ClinicalTrials.gov NCT01569503). Methods: Consecutive patients with moderate to severe (220calprotectin (FC), ileo-colonoscopy (CDEIS), contrast-enhanced ultrasound (CEUS), heart rate variability (HRV, a marker of the sympatho-vagal balance) were performed before VNS and during the follow-up for one year. Under general anesthesia, an electrode (Cyberonics, Lyon, France) was wrapped around the left VN in the neck, tunnelized subcutaneously, and connected to a pulse generator (Cyberonics) located subcutaneously in the left chest wall. The following parameters were used for VNS: 0.5 mA, 10 Hz, 30 s ON, 5 min OFF, continuous cycle. In case of aggravation, patients were removed from the study and treated with anti-TNF/immunosuppressants or surgery. Results: 4 patients have been included: 3 men/1 women; mean age: 42.5 years (32-50); Montreal classification (A3L1B2, A2L1B3, A2L2B1, A3L2B1); length of the disease (9.5 years; 0.5-26); smoking (2/4). Two patients were Naive of treatment on inclusion, one was under azathioprine (AZA) since 8 years and one had stopped AZA 3.5 years before. The mean CDAI at entrance was 335 (320-358), CRP: 78 (8-166), FC: 677 (20-1762), CEUS: active disease, CDEIS: 16 (8-30), vagal hypoactivity on HRV was observed in 3/4 patients and uninterpretable in one. Two patients are currently in clinical remission (CDAI<150) with mucosal healing (CDEIS: 3-0) with a respective follow-up of 20 and 8 months. The patient in deep remission under AZA+VNS stopped AZA after 14 months of VNS and is in remission after 6 months of follow-up. One patient presented an improvement of CDAI and FC but switched to surgery after 2.5 months of VNS because of a persistent CD activity with an entero-enteric fistula and abscess; the patient agreed to pursue VNS alone postsurgery and had endoscopic healing (i0) at 6 months post-surgery. The last patient switched to Infliximab (IFX) and AZA because of an uncontrolled disease after 3 months of VNS despite a transient improvement. Two patients significantly improved HRV vagal tone after 6 months of VNS but not the third one who switched to IFX+AZA. VNS was well tolerated and no patient withdrew from the study due to complications or side-effects. Conclusion: The preliminary data of this pilot study show the feasibility of VNS which was well tolerated and efficient in 2 patients currently in deep remission; one patient with a failure of VNS is in deep remission 6 months post-surgery. We are currently pursuing the study.