De Cruz P, Kamm M A, Hamilton A L, Ritchie K J, Krejany E O, Gorelik A, Liew D, Prideaux L, Lawrance I C, Andrews J M, Bampton P A, Jakobovits S, Florin T H, Gibson P R, Debinski H, Gearry R B, Macrae F A, Leong R W, Kronborg I, Radford-Smith G, Selby W, Johnston M J, Woods R, Elliott P R, Bell S J, Brown S J, Connell W R, Desmond P V
St Vincent's Hospital and University of Melbourne, Melbourne, Vic.
St Vincent's Hospital, Melbourne.
Aliment Pharmacol Ther. 2015 Oct;42(7):867-79. doi: 10.1111/apt.13353. Epub 2015 Aug 28.
Crohn's disease recurs in the majority of patients after intestinal resection.
To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence.
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.
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).
In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
大多数克罗恩病患者在肠道切除术后会复发。
比较硫唑嘌呤和抗TNF治疗在疾病复发高危患者中的相对疗效。
作为一项比较术后管理策略的更大规模研究的一部分，复发高危患者（吸烟者、穿孔性疾病、≥第二次手术）在切除所有肉眼可见病变后，接受3个月甲硝唑治疗，并联合2mg/kg/天硫唑嘌呤或1.5mg/kg/天巯嘌呤。硫唑嘌呤不耐受的患者先接受阿达木单抗诱导治疗，然后每两周注射40mg。患者在6个月时接受结肠镜检查，对治疗情况进行盲法评估内镜复发情况。
共纳入101例患者[男性占50%；中位（IQR）年龄36（25 - 46）岁]。硫唑嘌呤治疗组和阿达木单抗治疗组患者的疾病史无差异。15例患者在6个月前退出研究，5例因症状复发退出（其中4例接受了结肠镜检查）。73例硫唑嘌呤治疗患者中有33例（45%）出现内镜复发（ Rutgeerts评分i2 - i4），而28例阿达木单抗治疗患者中有6例（21%）出现内镜复发[意向性分析（ITT）；P = 0.028]；按方案分析（PPA）时，分别为62例中的24例（39%）和24例中的3例（13%）[P = 0.020]。完全黏膜内镜正常（Rutgeerts i0）在ITT分析中为17/73（23%） vs. 15/28（54%）（P = 0.003），PPA分析中为27% vs. 63%（P = 0.002）。最严重的疾病（Rutgeerts i3和i4）发生率在硫唑嘌呤组为8%，阿达木单抗组为4%。
在术后复发高危的克罗恩病患者中，阿达木单抗在预防早期疾病复发方面优于硫唑嘌呤。
