IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.
Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy.
Inflamm Bowel Dis. 2021 Jul 27;27(8):1237-1247. doi: 10.1093/ibd/izaa348.
Fecal lactoferrin (FL) levels may mirror drug-induced changes in inflammation in ulcerative colitis and Crohn disease in a timely way and could be used to assess loss of response (LOR) to biologics.
This study is a retrospective outcome review in 61 patients on adalimumab, infliximab, or vedolizumab managed in our center and followed for 6 to 24 months. Patients were 1) in clinical remission or 2) were experiencing possible LOR.
For group 1, in 71% of 31 patients, FL slowly increased during the therapeutic interval (R2 = 0.769; P < 0.001), thus reflecting increasing inflammation as drug concentrations decreased. In the remaining patients, FL was undetectable throughout the therapeutic interval because of a stronger suppression of inflammation. For group 2, in 30 patients negative for infections, FL levels measured 1 to 3 days after infusion/injection compared to preadministration values either increased (nonresponders)-in these patients the medication was switched to another class; partially decreased (partial responders)-the therapeutic interval was shortened; or were normal throughout (responders)-causes for symptoms unrelated to disease activity were found for all. After FL-based management, 3-month standardized clinical scores were normalized in both partial responders (0.58 ± 0.21 vs 0.13 ± 0.09; P < 0.001) and nonresponders (0.81 ± 0.17 vs 0.12 ± 0.08; P < 0.001), and FL levels dropped by up to 99%.
Levels of FL reflect drug-induced changes in mucosal inflammation in a timely way, thus enabling rapid assessment of therapeutic response in patients with ulcerative colitis and with Crohn disease. In patients with suspected LOR, FL levels before and after infusion/injection accurately separated responders, partial responders, and nonresponders. The strategy proposed here is simple, accurate, and easily applicable to clinical practice.
粪便乳铁蛋白（FL）水平可能及时反映溃疡性结肠炎和克罗恩病中药物诱导的炎症变化，可用于评估生物制剂的应答丢失（LOR）。
本研究回顾性分析了在我们中心接受阿达木单抗、英夫利昔单抗或维得利珠单抗治疗且随访 6 至 24 个月的 61 例患者的结局。患者分为 1）临床缓解，或 2）出现可能的 LOR。
对于组 1，31 例患者中 71%（22 例）的 FL 在治疗间隔期缓慢升高（R2=0.769；P<0.001），因此反映出随着药物浓度降低炎症逐渐加重。在其余患者中，由于炎症受到更强抑制，FL 在整个治疗间隔期均无法检测到。对于组 2，在 30 例无感染的患者中，与治疗前相比，输注/注射后 1 至 3 天的 FL 水平升高（无应答者）-这些患者换用另一种药物；部分降低（部分应答者）-缩短了治疗间隔期；或一直正常（应答者）-所有患者均找到了与疾病活动无关的症状的原因。基于 FL 管理后，部分应答者（0.58±0.21 比 0.13±0.09；P<0.001）和无应答者（0.81±0.17 比 0.12±0.08；P<0.001）的 3 个月标准化临床评分恢复正常，FL 水平下降高达 99%。
FL 水平及时反映了黏膜炎症的药物诱导变化，从而能够快速评估溃疡性结肠炎和克罗恩病患者的治疗反应。在疑似 LOR 的患者中，输注/注射前后的 FL 水平能够准确地区分应答者、部分应答者和无应答者。本研究提出的策略简单、准确，易于在临床实践中应用。
