Research

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing bowel disorders. Several established drug therapies exist, but some patients become resistant to these. For these patients, new treatments are urgently called for. Small studies have suggested that the immune system can be influenced by modulating the opioid receptors in the gut using Low Dose Naltrexone (LDN). Here, we report our experience with LDN in patients resistant to conventional therapies.

METHODS: A case series of all IBD outpatients treated with LDN (5 mg/day) were identified and investigated. Patients with at least 1 follow-up visit were included. Clinical and endoscopic response were analyzed where available. Clinical response was defined as clinical remission after 3 months of treatment. Endoscopic response was defined as a reduction of the endoscopic Mayo score to ≤1.

RESULTS: From June 2010 until June 2013, 40 patients (43% male, median age 40 years, IQR 28–52 years) were treated with LDN. Previous treatments included anti-TNF in 36 patients, immunomodulators in 39 patients and corticosteroids in 40 patients. At time of LDN start, 8 patients were on anti-TNF treatment, 12 received immunomodulators and 18 patients received corticosteroids. Follow-up is ongoing in 27 patients, the other 13 patients were followed for a median of 6 months (IQR 4–13 months). 22 patients had a diagnosis of CD and 18 had UC. Clinical response was achieved in 12 patients (30%), 8 CD (36%) and 4 UC (22%). 22 other patients (55%) had a response of limited duration (1 to 3 months), whereas 6 patients (15%) showed no response at all. Endoscopic data was available in 8 responders, with 7 showing endoscopic response. Endoscopic data of 13 non-responders was available, with none showing endoscopic improvement.

Amongst long term responders, remission was sustained for a median of 21 months (IQR 15–26 months). 9 patients are still in remission, the other 3 patients relapsed at 11, 21 and 21 months. In total, 11 patients underwent surgery (28%), 5 CD (4 subtotal colectomies, 1 partial small bowel resection) and 6 UC patients (all subtotal colectomies). Corticosteroids could be stopped in 13 patients. In total, 5 patients (12%) reported side-effects (headache, nightmares, dizziness), 1 patient stopped LDN treatment because of these.

CONCLUSION: Our data shows that for IBD patients refractory to conventional treatment, LDN may be a promising application - 30% of these severe cases responded to treatment, with 20% of patients showing lasting benefits. The relatively mild side-effects of LDN justify the consideration of this treatment for therapy-resistant IBD or as a bridge to surgery.