Background:
Post-operative disease recurrence occurs endoscopically in 90%, and clinically in 30% of Crohn's disease patients at one year. Mucosal recurrence is an excellent surrogate marker for the later development of clinical disease. There have been no direct comparisons of anti‑TNF therapy with thiopurine. This study aimed to assess the effect of adalimumab and thiopurine on mucosal disease recurrence prospectively and selectively in high risk patients.
Methods:
The Post Operative Crohn's Endoscopic Recurrence (POCER) study aims to assess in preventing recurrent disease the value of post-operative endoscopic assessment and treatment step up for early mucosal recurrence. Patients are stratified according to risk of recurrence (high risk = smoker, perforating disase, ≥ second operation). Post-operatively, all patients undergoing “curative” ileocecal resection receive 3 months metronidazole. High-risk patients also receive daily azathioprine 2 mg/kg or 6 mercaptopurine 1.5 mg/kg. High risk patients intolerant of thiopurine receive adalimumab 160 mg/80 mg and then 40 mg two weekly. Low-risk patients receive no further medication. Two thirds of patients undergo colonoscopy at 6 months, with endoscopic recurrence assessed blind to treatment arm. Endoscopic remission is defined as Rutgeerts score i0 or i1 (i0 = no lesions, i1 = mild small superficial anastomotic lesions), and recurrence defined as i2–i4 (moderate to severe lesions). In this first analysis, we have assessed the extent of mucosal recurrence at 6 months in high-risk patients who received either thiopurine or adalimumab immediately post-operatively.
Results:
Eighty-five patients (71 high and 14 low risk) have reached the 6 month time point to date. Of these 11 (10 high and 1 low risk) patients dropped out within the first 6 months prior to colonoscopy leaving 74 patients for this analysis. Of the 74 patients 61 patients (82% of the cohort, 52% male, median age 35 years) were high-risk and form the basis of this preliminary report. Metronidazole was tolerated by 57 (93%) of patients. Forty five (74%) high-risk patients tolerated and hence continued thiopurine of whom 28 (62%) were in endoscopic remission at 6 months (Rutgeerts i0 or i1). Of the 16 (26%) patients on adalimumab 15 (93.8%) were in endoscopic remission (P = 0.024 high risk patients thiopurine v adalimumab).
Conclusions:
In high-risk patients, adalimumab prevents recurrent mucosal disease in almost all patients, and is superior to thiopurine.
