Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients - a POCER study analysis.

Abstract

BACKGROUND:

Crohn's disease recurs in the majority of patients after intestinal resection.

AIM:

To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence.

METHODS:

As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment.

RESULTS:

A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab).

CONCLUSIONS:

In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

• Authors: P De Cruz, M A Kamm, A L Hamilton, K J Ritchie, E O Krejany, A Gorelik, D Liew, L Prideaux, I C Lawrance, J M Andrews, P A Bampton, S Jakobovits, T H Florin, P R Gibson, H Debinski, R B Gearry, F A Macrae, R W Leong, I Kronborg, G Radford-Smith, W Selby, M J Johnston, R Woods, P R Elliott, S J Bell, S J Brown, W R Connell, P V Desmond
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 42 Issue 7 Pg. 867-79 (Oct 2015) ISSN: 1365-2036 [Electronic] England
• PMID: 26314275 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Tumor Necrosis Factor-alpha
• Metronidazole
• Mercaptopurine
• Adalimumab
• Azathioprine

Topics

• Adalimumab (therapeutic use)
• Adult
• Aged
• Azathioprine (administration & dosage, adverse effects)
• Colonoscopy (methods)
• Crohn Disease (diagnosis, prevention & control, surgery)
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Male
• Mercaptopurine (administration & dosage, adverse effects)
• Metronidazole (administration & dosage, adverse effects)
• Middle Aged
• Postoperative Period
• Recurrence
• Risk Factors
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, immunology)