Emily K Wright1, Michael A Kamm2, Peter De Cruz1, Amy L Hamilton1, Kathryn J Ritchie3, Efrosinia O Krejany3, Steven Leach4, Alexandra Gorelik5, Danny Liew5, Lani Prideaux1, Ian C Lawrance6, Jane M Andrews7, Peter A Bampton8, Simon L Jakobovits9, Timothy H Florin10, Peter R Gibson9, Henry Debinski11, Finlay A Macrae12, Douglas Samuel13, Ian Kronborg14, Graeme Radford-Smith15, Warwick Selby16, Michael J Johnston3, Rodney Woods3, P Ross Elliott3, Sally J Bell3, Steven J Brown3, William R Connell3, Andrew S Day17, Paul V Desmond1, Richard B Gearry18. 1. Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia. 2. Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia. Electronic address: mkamm@unimelb.edu.au. 3. Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia. 4. School of Women's and Children's Health, University of New South Wales, Sydney, Australia. 5. Melbourne EpiCentre, University of Melbourne, Melbourne, Australia. 6. Centre for Inflammatory Bowel Diseases, Fremantle Hospital, Freemantle, Australia; The University of Western Australia, Fremantle, Australia. 7. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia; University of Adelaide, Adelaide, Australia. 8. Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, Australia; Flinders University, Adelaide, Australia. 9. Department of Gastroenterology, Alfred Health, Melbourne, Australia; Monash University, Melbourne, Australia. 10. Department of Gastroenterology, Mater Health Services, Brisbane, Australia. 11. Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, Australia. 12. University of Melbourne, Melbourne, Australia; Department of Colorectal Medicine and Genetics, and Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia. 13. Department of Gastroenterology, Bankstown Hospital, Sydney, Australia. 14. Department of Gastroenterology, Western Hospital, Melbourne, Australia. 15. IBD Group Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia; Department of Gastroenterology, Royal Brisbane and Womens Hospital, Brisbane, Australia. 16. AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia. 17. Department of Paediatrics, University of Otago, Christchurch, New Zealand. 18. Department of Medicine, University of Otago, Christchurch, New Zealand.
Abstract
BACKGROUND & AIMS: Crohn's disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa. METHODS: We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients. RESULTS:Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 μg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 μg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months. CONCLUSIONS: In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.
RCT Entities:
BACKGROUND & AIMS:Crohn's disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa. METHODS: We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients. RESULTS: Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 μg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 μg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months. CONCLUSIONS: In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059