Hoekman Daniël R, Brandse Johannan F, de Meij Tim G, Hummel Thalia Z, Löwenberg Mark, Benninga Marc A, D'Haens Geert R, Kindermann Angelika
Department of Pediatric Gastroenterology and Nutrition, Academic Medical Center , Amsterdam , The Netherlands.
Scand J Gastroenterol. 2015;50(9):1110-7. doi: 10.3109/00365521.2015.1027264. Epub 2015 Apr 11.
Low serum trough levels (TLs) of infliximab (IFX) and antibodies to IFX (ATIs) are associated with the loss of therapeutic response in adults with inflammatory bowel disease (IBD) receiving IFX. Until now, pediatric data are scarce. Therefore, we aimed to cross-sectionally investigate the association between ATIs and IFX TLs, and clinical and biochemical disease activity in children receiving IFX for IBD.
Children aged <18 years receiving IFX maintenance treatment for Crohn's disease (CD) or ulcerative colitis (UC) at three Dutch hospitals were included. Prior to two consecutive IFX infusions, IFX TLs and ATI levels were measured. Clinical disease activity was determined by Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI), for CD and UC, respectively. Biochemical disease activity was assessed by serum C-reactive protein (CRP) and fecal calprotectin (FC). Clinical remission was defined as a PUCAI or PCDAI score of <10. Therapeutic range of IFX was considered 3-7 µg/ml.
Thirty-nine patients were included (31 CD; 16 females). Median age was 15 years. Median IFX TL was 3.5 µg/ml [IQR 2-7]. Subtherapeutic and supratherapeutic TLs were found in 38% and 23% of children, respectively. ATIs were detected in four patients. A correlation was found between IFX TL and CRP [rs = -0.51; p < 0.01] and FC [rs = -0.49; p < 0.01]. However, when only clinical disease activity was considered, no difference in median TL was found between remission and active disease (resp. 3.5 µg/ml [IQR 2-5] and 2.3 µg/ml [IQR 0.3-4.6]; p = 0.2).
IFX TLs are related to biochemical markers of disease activity. This could provide a rationale for monitoring TLs in children receiving IFX for IBD.
英夫利昔单抗（IFX）的低血清谷浓度（TLs）及抗英夫利昔单抗抗体（ATIs）与接受IFX治疗的成年炎症性肠病（IBD）患者治疗反应丧失相关。目前，儿科数据匮乏。因此，我们旨在横断面研究接受IFX治疗IBD的儿童中ATIs与IFX TLs之间的关联，以及临床和生化疾病活动情况。
纳入在荷兰三家医院接受IFX维持治疗克罗恩病（CD）或溃疡性结肠炎（UC）的18岁以下儿童。在连续两次IFX输注前，测量IFX TLs和ATI水平。分别采用儿科克罗恩病活动指数（PCDAI）和儿科溃疡性结肠炎活动指数（PUCAI）确定CD和UC的临床疾病活动度。通过血清C反应蛋白（CRP）和粪便钙卫蛋白（FC）评估生化疾病活动度。临床缓解定义为PUCAI或PCDAI评分<10。IFX的治疗范围为3 - 7μg/ml。
纳入39例患者（31例CD；16例女性）。中位年龄为15岁。中位IFX TL为3.5μg/ml[四分位间距2 - 7]。分别在38%和23%的儿童中发现低于治疗范围和高于治疗范围的TLs。4例患者检测到ATIs。发现IFX TL与CRP[rs = -0.51；p < 0.01]和FC[rs = -0.49；p < 0.01]之间存在相关性。然而，仅考虑临床疾病活动度时，缓解期和疾病活动期的中位TL无差异（分别为3.5μg/ml[四分位间距2 - 5]和2.3μg/ml[四分位间距0.3 - 4.6]；p = 0.2）。
IFX TLs与疾病活动度的生化标志物相关。这可为监测接受IFX治疗IBD的儿童的TLs提供理论依据。
