Strategic timing of anti-TNF therapy in postoperative Crohn's disease: Comparison of routine use immediately postoperatively with selective use after demonstrated recurrence at 6 month endoscopy. Results from POCER

Abstract

Introduction: Recent data suggest that anti-TNF therapy prevents post-operative recurrence of Crohn’s disease. Routine postoperative use is costly and may lead to overtreatment; an alternative may be selective use for early endoscopic recurrence. These strategies have been compared with mucosal healing as the goal in this “treat to target” study. Methods: In the Post Operative Crohn’s Endoscopic Recurrence, “POCER” study, after resection patients were stratified for risk of recurrence as high (smoker, perforating disease,≥2nd operation) or low risk. All patients received 3 months metronidazole 400 mg bd. High risk patients also received daily azathioprine 2 mg/kg or 6 mercaptopurine 1.5 mg/kg, or adalimumab 40 mg fortnightly if thiopurine intolerant. Patients were randomised to endoscopy at 6 months or no endoscopy; endoscopic remission defined as Rutgeerts score i0 or i1 & recurrence as≥i2. For endoscopic recurrence at 6 months high risk patients on thiopurine stepped up to adalimumab 40 mg fortnightly, & high risk thiopurine-intolerant patients stepped up to weekly adalimumab. All patients were colonoscoped at 18months: the primary endpoint endoscopic recurrence. In this intent-to-treat sub-analysis we compared the 18 month outcomes of high risk patients in the endoscopy arm on immediate postoperative adalimumab to those initially on thiopurine who stepped-up to combined adalimumab+thiopurine for recurrence at 6 months. Results: Endoscopic recurrence at 18 months occurred in 12/28 (43%)patients on adalimumab immediately postoperatively compared to19/32 (59%) patients initially on thiopurine who stepped up to adalimumab+thiopurine at 6 months; P=0.20. Complete mucosal normality (i0) occurred in 9/28 (32%) v 7/32 (22%); P=0.37. Severe disease(i3 & i4) occurred in 3/28 (11%) v 3/32 (9%); P=NS. Conclusions: Recurrence did not differ significantly between immediate postoperative adalimumab & step-up adalimumab at 6 months for endoscopic recurrence, although the former tended to be more effective. There was minimal difference in rates of severe disease recurrence between the two strategies. Step-up with anti-TNF therapy based on endoscopic findings is a viable postoperative strategy in patients at high risk of recurrence.