P De Cruz1, M A Kamm1, A L Hamilton1, K J Ritchie2, E O Krejany1, A Gorelik3, D Liew3, L Prideaux1, I C Lawrance4, J M Andrews5, P A Bampton6, S Jakobovits7, T H Florin8, P R Gibson7, H Debinski9, R B Gearry10, F A Macrae11, R W Leong12, I Kronborg13, G Radford-Smith14, W Selby15, M J Johnston2, R Woods2, P R Elliott2, S J Bell1, S J Brown2, W R Connell2, P V Desmond2. 1. St Vincent's Hospital and University of Melbourne, Melbourne, Vic. 2. St Vincent's Hospital, Melbourne. 3. Melbourne EpiCentre, Royal Melbourne Hospital, Melbourne. 4. University of Western Australia, Fremantle. 5. Royal Adelaide Hospital, Adelaide. 6. Flinders Medical Centre and Flinders University, Bedford Park, SA, Australia. 7. Alfred Health and Monash University, Melbourne, Vic., Australia. 8. University of Queensland, St Lucia. 9. Cabrini Hospital, Melbourne. 10. Christchurch Hospital, Christchurch, New Zealand. 11. Colorectal Medicine and Genetics, Royal Melbourne Hospital, Melbourne. 12. Gastroenterology and Liver Services, Concord Hospital, Sydney. 13. Western Hospital, Melbourne. 14. Queensland Institute of Medical Research and University of Queensland School of Medicine, Herston Campus, Brisbane. 15. Royal Prince Alfred Hospital, Sydney.
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 monthsmetronidazole 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.
RCT Entities:
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 diseasepatients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
Authors: G Pellino; D S Keller; G M Sampietro; I Angriman; M Carvello; V Celentano; F Colombo; F Di Candido; S Laureti; G Luglio; G Poggioli; M Rottoli; S Scaringi; G Sciaudone; G Sica; L Sofo; S Leone; S Danese; A Spinelli; G Delaini; F Selvaggi Journal: Tech Coloproctol Date: 2020-03-14 Impact factor: 3.781
Authors: Anthony O'Connor; Peter J Hamlin; Jennifer Taylor; Christian Selinger; Nigel Scott; Alexander C Ford Journal: Frontline Gastroenterol Date: 2016-12-01
Authors: Kelly C Cushing; Richard Mclean; Keely G McDonald; Jenny K Gustafsson; Kathryn A Knoop; Devesha H Kulkarni; R Balfour Sartor; Rodney D Newberry Journal: Inflamm Bowel Dis Date: 2019-01-01 Impact factor: 5.325