前瞻性儿科比利时克罗恩病登记研究（BELCRO）：抗 TNF 治疗的长期结果和加速升级策略。
Long-term Outcomes with Anti-TNF Therapy and Accelerated Step-up in the Prospective Pediatric Belgian Crohn's Disease Registry (BELCRO).
机构信息
1Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium; 2Pediatric Gastroenterology, UCL St Luc, Brussels, Belgium; 3Pediatric Gastroenterology, UZ Brussel, Brussels, Belgium; 4Pediatric Gastroenterology, HUDERF, Brussels, Belgium; 5Pediatric Gastroenterology, UZ Leuven, Leuven, Belgium; 6Pediatric Gastroenterology, Jessa Ziekenhuis, Hasselt, Belgium; 7Pediatric Gastroenterology, ZOL Genk, Genk, Belgium; 8Gastroenterology, ST Lucas, Ghent, Belgium; 9Pediatric Gastroenterology, UZ Gent, Ghent, Belgium; 10Pediatric Gastroenterology, CHC Liège, Liège, Belgium; 11Pediatric Gastroenterology, UZ Antwerpen, Antwerp, Belgium; 12Gastroenterology, UZ Gent, Ghent, Belgium; 13Gastroenterology, Imelda Ziekenhuis, Bonheiden, Belgium; 14Gastroenterology, UCL Mont Godinne, Mont Godinne, Belgium; 15Gastroenterology, UCL St Luc, Brussels, Belgium; 16Gastroenterology, ULB Erasme, Brussels, Belgium; 17Gastroenterology, CHU Liège, Liège, Belgium; 18Gastroenterology, St Pierre, Ottignies, Belgium; 19Gastroenterology, Heilig Hart Ziekenhuis, Roeselaere, Belgium; and 20DNA Lytics, Louvain-la-Neuve, Belgium.
出版信息
Inflamm Bowel Dis. 2017 Sep;23(9):1584-1591. doi: 10.1097/MIB.0000000000001193.
BACKGROUND
Accelerated step-up or anti-tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohn's disease.
METHODS
Five-year follow-up data from a prospective observational cohort of children diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF-exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission.
RESULTS
A total of 91 patients (median [IQR] age 12.7 [10.9-14.8] yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF-exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 [11.5-15.2] versus 11.8 [8.7-13.8] yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 [1.4-1.9] versus 1.4 [1.3-1.6]; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1-15.9] versus 12.5 [10.2-14.1]; P = 0.02) and average disease severity (1.8 [1.6-1.9] versus 1.6 [1.3-1.8]; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported.
CONCLUSIONS
Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.
背景
目前不建议在儿科克罗恩病的首次缓解前加速升级或使用肿瘤坏死因子（TNF）拮抗剂。
方法
对在比利时被诊断为克罗恩病的儿童进行前瞻性观察队列的 5 年随访数据进行分析。疾病严重程度评分分为不活跃、轻度和中重度。如果持续≥2 年，则定义为缓解或不活跃疾病。在接受 TNF 拮抗剂治疗的患者和未接受 TNF 拮抗剂治疗的患者之间以及在首次缓解前和首次缓解后使用 TNF 拮抗剂之间进行了单变量分析，并评估了与主要结局（平均疾病严重程度和持续缓解）的相关性。
结果
共纳入 91 例患者（中位数[IQR]年龄 12.7[10.9-14.8]岁，53%为男性）。疾病部位为 12%为 L1，23%为 L2，64%为 L3，76%有上消化道受累，30%有肛周受累。疾病严重程度为 25%为轻度，75%为中重度。在 66 例（73%）接受 TNF 拮抗剂治疗的患者中，34 例（52%）进行了加速升级。TNF 拮抗剂的使用与年龄（13.1[11.5-15.2]岁与 11.8[8.7-13.8]岁；P＜0.05）、L2（29%与 8%；P=0.04）和平均疾病严重程度（1.7[1.4-1.9]与 1.4[1.3-1.6]；P＜0.001）有关。TNF 拮抗剂的使用时间与平均疾病严重程度相关（r=0.32，P=0.002）。加速升级也与年龄（13.3[12.1-15.9]岁与 12.5[10.2-14.1]岁；P=0.02）和平均疾病严重程度（1.8[1.6-1.9]与 1.6[1.3-1.8]；P=0.002）有关。所有患者的持续缓解时间相似，且未报告严重感染、癌症或死亡。
结论
在疾病更严重的老年患者中使用 TNF 拮抗剂治疗和加速升级可带来长期获益。
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