OP023. Optimising post-operative Crohn's disease management: Best drug therapy alone versus endoscopic monitoring, disease evolution, and faecal calprotectin monitoring. The POCER study
M.A. Kamm, P.P. De Cruz, E.K. Wright, 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.L. Jakobovits, T.H. Florin, P.R. Gibson, H.S. Debinski, A.S. Day, R.B. Gearry, F.A. Macrae, D. Samuel, R.W. Leong, I.J. Kronborg, G.L. Radford-Smith, W.S. Selby, M.J. Johnson, R.J. Woods, P.R. Elliott, S.J. Bell, S.J. Brown, W.R. Connell, P.V. Desmond, St Vincent's Hospital & University of Melbourne, Gastroenterology, Melbourne, Australia
Disease recurs in most Crohn's disease patients after intestinal resection, with endoscopic recurrence preceding clinical recurrence. We investigated (i) whether early endoscopic monitoring with treatment step-up for endoscopic recurrence is superior to standard drug therapy alone; (ii) disease evolution under optimal drug therapy - is it possible to regain remission after endoscopic recurrence and is ongoing monitoring needed after early remission? (iii) whether faecal calprotectin (FC) can substitute for endoscopic monitoring.
This IIS Post-Operative Crohn's Endoscopic Recurrence (POCER) treat-to-target study aimed for mucosal healing. All patients received 3 months metronidazole. High risk patients (smoker, perforating disease, ≥2nd operation) also received daily thiopurine, or adalimumab if thiopurine intolerant. Patients were randomised 2:1 to colonoscopy at 6 months (“active care”) or no colonoscopy (“standard care”). Endoscopic remission was defined as Rutgeerts score i0 or i1 and recurrence as ≥i2. For endoscopic recurrence at 6 months low risk patients stepped up to thiopurine, high risk patients stepped up to adalimumab fortnightly, and high risk thiopurine-intolerant patients stepped up to weekly adalimumab. All patients were colonoscoped at 18 months, scored centrally blind to treatment, with primary end-point endoscopic recurrence at 18 months. FC (319 samples) CRP and CDAI were measured pre-operatively, and at 6, 12, & 18 months.
174 patients (83% high risk) in 21 hospitals enrolled. Of 122 active care patients 39% underwent 6 month treatment step-up. 18 months endoscopic recurrence occurred in 49% active care v 67% standard care patients (P = 0.028). Step up at 6 months brought 38% of patients with endoscopic recurrence into remission 1 year later; conversely endoscopic disease recurred 1 year later in 41% of patients who were in remission at 6 months. FC correlated with endoscopic recurrence (r = 0.42, p < 0.001) and score (r = 0.44, p < 0.001); CRP and CDAI did not. FC >100mcg/g indicated endoscopic recurrence with a sensitivity 0.89 and NPV 91%, potentially allowing avoidance of colonoscopy in 41% of patients.
Treating according to risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is superior to optimal drug therapy alone in preventing post-op disease recurrence. Selective immunosuppression, with colonoscopy-based adjustment, rather than its use in all high risk patients, leads to effective disease control in a majority. Early endoscopic remission requires ongoing monitoring. FC can be used to monitor for recurrence and is superior to CRP and CDAI.