Shaare Zedek Medical Center, Jerusalem, Israel.
Inflamm Bowel Dis. 2010 Mar;16(3):469-73. doi: 10.1002/ibd.21070.
The pathophysiological basis for corticosteroid (CS) failure in ulcerative colitis (UC) is unknown. A transactivation glucocorticoid bioassay (GBA) was developed to measure the biological activity of CS by quantifying glucocorticoid response elements. This approach eliminates differences in bioavailability, chemistry, affinity, and other potential differences between the various steroids regarding their ability to activate the glucocorticoid receptor. In this multicenter prospective study, we aimed to evaluate whether CS bioavailability plays a role in CS refractoriness in severe pediatric UC.
GBA (using COS-1 transfected cells) was measured in the serum of 50 children (52% males, age 13.4 +/- 3.5 years) admitted for acute severe UC on the third day of CS treatment. Demographic, clinical, and laboratory data were prospectively recorded.
Of the children enrolled, 16 (32%) failed CS therapy and required infliximab (n = 14) or colectomy (n = 2) within a median of 10 days (interquartile range [IQR] 6.5-14.5). Reflecting internal validity of the assay, GBA was highly correlated with the last CS dose and the time interval to bloodletting (r = -0.41 and r = -0.54, respectively; P < 0.001). There was no statistically significant difference in the GBA levels between responders and nonresponders (249 nM versus 200 nM cortisol equivalent, P = 0.18). In a multivariate regression model adjusted for time elapsed from CS and the administered dose, GBA did not predict response to CS (P = 0.34).
The lack of correlation of GBA level and treatment outcome lends support to the hypothesis that the bioavailability, type, and dosing of intravenous CS are not associated with response or failure to the drug.
溃疡性结肠炎（UC）中皮质类固醇（CS）治疗失败的病理生理基础尚不清楚。一种糖皮质激素激活生物测定法（GBA）被开发出来，通过量化糖皮质激素反应元件来测量 CS 的生物活性。这种方法消除了各种类固醇在生物利用度、化学性质、亲和力和其他潜在差异方面的差异，这些差异可能会影响它们激活糖皮质激素受体的能力。在这项多中心前瞻性研究中，我们旨在评估 CS 生物利用度是否在严重儿科 UC 中 CS 抵抗中起作用。
在 CS 治疗第 3 天入院的 50 名儿童（52%为男性，年龄 13.4 ± 3.5 岁）的血清中测量 GBA（使用 COS-1 转染细胞）。前瞻性记录人口统计学、临床和实验室数据。
在纳入的儿童中，16 名（32%）CS 治疗失败，需要在中位数 10 天内（IQR 6.5-14.5）接受英夫利昔单抗（n=14）或结肠切除术（n=2）。反映了该测定的内部有效性，GBA 与 CS 的最后剂量和采血时间间隔高度相关（r=-0.41 和 r=-0.54，P<0.001）。反应者和无反应者之间的 GBA 水平没有统计学差异（249 nM 与 200 nM 皮质醇当量，P=0.18）。在调整 CS 时间和给药剂量的多变量回归模型中，GBA 不能预测 CS 的反应（P=0.34）。
GBA 水平与治疗结果之间缺乏相关性，这支持了这样一种假设，即静脉 CS 的生物利用度、类型和剂量与药物的反应或失败无关。
