Hemperly Amy, Dubinsky Marla C, Yarur Andres, Afzali Anita, Hanauer Stephen, Kugathasan Subra, Long Millie D, Rabizadeh Shervin, Sockolow Robbyn, Okada Lauren, Jain Anjali, Abreu Maria T, Vande Casteele Niels
Department of Pediatrics, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
Rady Children's Hospital, San Diego, California, USA.
Crohns Colitis 360. 2021 Jun 9;3(3):otab035. doi: 10.1093/crocol/otab035. eCollection 2021 Jul.
Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibody concentrations is used to optimize tumor necrosis factor antagonists (anti-TNF). The endoscopic healing index (EHI) is a validated serum-based assay to measure mucosal inflammation in adults with Crohn disease (CD). Our objectives were to evaluate the relationship between EHI and TDM results and to determine the anti-TNF concentration range associated with EHI <20 (consistent with endoscopic remission).
Adult and pediatric patients with CD (N = 1731) were selected retrospectively from a clinical laboratory cohort. Patients were selected if they had an ICD-10 code for CD and if results for EHI and TDM were available within 30 days of each other. The relationship between EHI and TDM results was examined and the anti-TNF concentration range associated with EHI <20 vs >50 was evaluated.
Median anti-TNF concentration was higher in patients with EHI <20 vs >50 for infliximab (N = 796): 11.1 vs 3.4 µg/mL and for adalimumab (N = 935): 9.2 vs 5.0 µg/mL ( < 0.0001 both drugs). Patients with antibodies to infliximab (12.8%) or adalimumab (14.9%) had lower anti-TNF concentrations ( < 0.001 both drugs) and higher EHI ( < 0.01 both drugs). The concentration range for infliximab: 5-15 µg/mL (5-9 µg/mL in pediatric patients) and for adalimumab: 5-10 µg/mL (8 µg/mL in pediatric patients) best discriminated EHI <20 vs >50.
We report the anti-TNF concentration range associated with EHI <20. Combined testing of EHI and TDM is proposed as a noninvasive approach for treat-to-target management which could improve the ability to monitor disease and optimize anti-TNF therapy.
通过测定血清药物及抗药物抗体浓度进行治疗药物监测（TDM），以优化肿瘤坏死因子拮抗剂（抗TNF）的治疗效果。内镜愈合指数（EHI）是一种经过验证的基于血清的检测方法，用于测量克罗恩病（CD）成年患者的黏膜炎症。我们的目标是评估EHI与TDM结果之间的关系，并确定与EHI<20（与内镜缓解一致）相关的抗TNF浓度范围。
从临床实验室队列中回顾性选取成年和儿科CD患者（N = 1731）。入选患者需有CD的ICD - 10编码，且EHI和TDM结果在彼此30天内可得。检查EHI与TDM结果之间的关系，并评估与EHI<20对比>50相关的抗TNF浓度范围。
对于英夫利昔单抗（N = 796），EHI<20的患者中位抗TNF浓度高于EHI>50的患者：分别为11.1 vs 3.4 μg/mL；对于阿达木单抗（N = 935），分别为9.2 vs 5.0 μg/mL（两种药物均P<0.0001）。有英夫利昔单抗抗体（12.8%）或阿达木单抗抗体（14.9%）的患者抗TNF浓度较低（两种药物均P<0.001）且EHI较高（两种药物均P<0.01）。英夫利昔单抗的浓度范围：5 - 15 μg/mL（儿科患者为5 - 9 μg/mL），阿达木单抗的浓度范围：5 - 10 μg/mL（儿科患者为8 μg/mL）对EHI<20与>50的区分最佳。
我们报告了与EHI<20相关的抗TNF浓度范围。建议联合检测EHI和TDM作为一种无创的达标治疗管理方法，这可能提高疾病监测能力并优化抗TNF治疗。
