Yale School of Medicine, Section of Digestive Diseases, New Haven, CT, United States; Department of Internal Medicine, Section of Gastroenterology and Hepatology, King Faisal Specialist Hospital, Riyadh, Saudi Arabia.
Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United States.
Clin Biochem. 2023 Sep;119:110618. doi: 10.1016/j.clinbiochem.2023.110618. Epub 2023 Jul 26.
There are multiple assays for infliximab (IFX) drug level (IFX-DL) and antibody to infliximab (ATI) measurement. The aims of this study are to examine the correlation and outcomes of IFX-DL and ATI in inflammatory bowel disease (IBD) patients, simultaneously measured with different methods in different institutions.
Residual samples of IFX-treated IBD patients undergoing drug monitoring for IFX-DL and ATI, both measured by ECLIA (Esoterix Laboratories) were used to simultaneously quantify IFX-DL via LC-MS/MS and ATI via an in-house ECLIA (ih-ECLIA) (Mayo Clinic Laboratories). Comparisons of IFX-DL and ATI detection between the assays from different institutions were performed, along with a comparison between the assays by association of IFX-DL and ATI obtained by each method with clinical remission, endoscopic healing (EH) and normal serum C-reactive protein (CRP ≤ 8 mg/L).
A total of 151 patients were included (median age, 32 years (range, 12-84); 45.7% female). The median IFX-DL was 7 mcg/mL (IQR: 1.3, 19.4) and 6 mcg/mL (IQR: 0.9, 20) via LC-MS/MS and ECLIA, respectively (Spearman correlation coefficient r = 0.97). ATI was detected in 13/142 (9.2%) via ih-ECLIA of whom 100% had IFX-DL < 5 mcg/mL by LC-MS/MS. ATI was positive in 39/151 (25.8%) via ECLIA, and 84.6% of positives had IFX-DL < 5 mcg/mL by ECLIA. Compared to ECLIA, the frequency of ATI detection via ih-ECLIA was lower in patients in clinical remission (7.3% vs 36.6%; p = 0.0005), those with normal CRP (5.9% vs. 20.0%; p = 0.0005), and in patients with EH (5.3% vs 18.4%; p = 0.03).
IFX-DL was comparable between LC-MS/MS and ECLIA assays. Rate of ATI detection via ih-ECLIA was lower than ECLIA, which was more aligned with favorable clinical outcomes.
有多种用于英夫利昔单抗（IFX）药物浓度（IFX-DL）和抗英夫利昔单抗（ATI）检测的检测方法。本研究的目的是同时检测不同机构使用不同方法测量的炎症性肠病（IBD）患者的 IFX-DL 和 ATI，并探讨其相关性和结果。
利用酶联免疫吸附试验（ECLIA）（Esoterix 实验室）同时检测的残留样本，对正在接受 IFX-DL 和 ATI 药物监测的 IFX 治疗的 IBD 患者进行检测，该样本同时通过 LC-MS/MS 定量 IFX-DL，通过内部 ECLIA（ih-ECLIA）（Mayo 诊所实验室）定量 ATI。对不同机构的检测方法进行 IFX-DL 和 ATI 检测的比较，并通过每种方法获得的 IFX-DL 和 ATI 与临床缓解、内镜愈合（EH）和正常血清 C 反应蛋白（CRP≤8mg/L）的相关性比较。
共纳入 151 例患者（中位年龄 32 岁[范围：12-84]；45.7%为女性）。通过 LC-MS/MS 和 ECLIA 检测到的 IFX-DL 中位数分别为 7 mcg/mL（IQR：1.3，19.4）和 6 mcg/mL（IQR：0.9，20）（Spearman 相关系数 r=0.97）。通过 ih-ECLIA 检测到 13/142（9.2%）例患者存在 ATI，其中 100%通过 LC-MS/MS 检测到 IFX-DL<5mcg/mL。通过 ECLIA 检测到 39/151（25.8%）例患者存在 ATI，其中 84.6%的阳性患者通过 ECLIA 检测到 IFX-DL<5mcg/mL。与 ECLIA 相比，ih-ECLIA 检测到的 ATI 频率在临床缓解患者中较低（7.3%比 36.6%；p=0.0005），在 CRP 正常患者中较低（5.9%比 20.0%；p=0.0005），在 EH 患者中较低（5.3%比 18.4%；p=0.03）。
LC-MS/MS 和 ECLIA 检测方法的 IFX-DL 结果具有可比性。通过 ih-ECLIA 检测到 ATI 的频率低于 ECLIA，这与更好的临床结局更为一致。
