Aparato Digestivo, Hospital Reina Sofía, España.
Farmacia Hospitalaria, Hospital Reina Sofía, España.
Rev Esp Enferm Dig. 2021 Feb;113(2):110-115. doi: 10.17235/reed.2020.7124/2020.
numerous studies have shown a positive correlation between serum biologic drug concentrations and favorable therapeutic outcomes during the induction and maintenance period in patients with Crohn's disease (CD). To our knowledge, only a few and contradictory studies have determined the association between ustekinumab (UST) trough concentrations and biological outcomes. This study aimed to investigate the relationship between ustekinumab trough concentrations and biological outcomes in a real-world setting.
a cross-sectional cohort study was performed. All adult patients with CD who received maintenance therapy (≥ 24 weeks) with ustekinumab were included in the study. Clinical response was determined using the Harvey-Bradshaw Index. Biochemical remission was defined as a fecal calprotectin level < 150 µg/g in feces and a biochemical response as > 50 % reduction of fecal calprotectin.
a total of 58 CD patients were included in the study and the median UST trough concentration was 1.78 µg/ml (IQR: 2.56). Differences in ustekinumab trough concentrations were observed for clinical (2.25 µg/ml vs 0.65 µg/ml; p = 0.006) and biochemical remission (2.33 µg/ml vs 1.03 µg/ml; p = 0.047). According to ROC analysis, a cut-off of 1.4 µg/ml (AUC: 077) and 2.0 µg/ml (AUC: 0.65) were identified for predicting clinical and biochemical remission, respectively. Likewise, ustekinumab trough levels were also higher in "composite clinical/biochemical remission" (2.38 µg/ml vs 1.08 µg/ml; p = 0.042). The trough level that was best associated with composite clinical/biochemical remission was 2.2 µg/ml (AUC: 0.69).
this real-life study shows the association between ustekinumab trough concentration and clinical and biochemical remission and we suggest an optimal cut-off point higher than 2.2 µg/ml. Further studies are needed to confirm the findings and to identify the optimal cut-off in different disease outcomes and disease phenotypes.
许多研究表明，在克罗恩病（CD）患者的诱导和维持期，血清生物药物浓度与良好的治疗效果呈正相关。据我们所知，只有少数几项相互矛盾的研究确定了乌司奴单抗（UST）谷浓度与生物治疗效果之间的关系。本研究旨在探讨真实环境中乌司奴单抗谷浓度与生物治疗效果之间的关系。
进行了一项横断面队列研究。所有接受乌司奴单抗维持治疗（≥24 周）的 CD 成年患者均纳入研究。临床反应采用 Harvey-Bradshaw 指数确定。生化缓解定义为粪便中粪钙卫蛋白水平<150μg/g，生化反应定义为粪钙卫蛋白降低>50%。
共纳入 58 例 CD 患者，乌司奴单抗谷浓度中位数为 1.78μg/ml（IQR：2.56）。临床（2.25μg/ml 比 0.65μg/ml；p=0.006）和生化缓解（2.33μg/ml 比 1.03μg/ml；p=0.047）方面观察到乌司奴单抗谷浓度存在差异。根据 ROC 分析，确定了 1.4μg/ml（AUC：0.77）和 2.0μg/ml（AUC：0.65）作为预测临床和生化缓解的截断值。同样，在“复合临床/生化缓解”中，乌司奴单抗谷浓度也较高（2.38μg/ml 比 1.08μg/ml；p=0.042）。与复合临床/生化缓解最相关的谷浓度为 2.2μg/ml（AUC：0.69）。
这项真实世界的研究表明了乌司奴单抗谷浓度与临床和生化缓解之间的关系，我们建议将最佳截断值设定在 2.2μg/ml 以上。需要进一步研究来证实这些发现，并确定不同疾病结局和疾病表型的最佳截断值。
