Bodini Giorgia, Demarzo Maria Giulia, Saracco Margherita, Coppo Claudia, De Maria Costanza, Baldissarro Isabella, Savarino Edoardo, Savarino Vincenzo, Giannini Edoardo G
Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Gastroenterolgy Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Scand J Gastroenterol. 2019 Oct;54(10):1220-1225. doi: 10.1080/00365521.2019.1666914. Epub 2019 Sep 25.
Up to 40% of inflammatory bowel disease (IBD) patients treated with anti-TNF drugs lose response within 1 year of treatment, therefore requiring drug optimization. Although higher drug trough levels (TLs) are associated with sustained clinical outcomes, there are concerns that they may be associated with a higher risk of adverse events (AEs). The aim was to evaluate the presence of a possible association between drug TLs and the occurrence of AEs in IBD patients treated with anti-TNF drugs. We retrospectively studied a cohort of 113 IBD patients treated with adalimumab or infliximab, of whom 27 were in combination therapy with immunosuppressants. TLs were measured using a homogeneous mobility shift assay. During a median follow-up of 16 months (range 1-144), we observed 103 AEs occurring in 58 patients. We found no statistically significant difference ( = .21) in median TLs between patients who did 6.7 mcg/mL; range 0.0-36.2) or did not (7.7 mcg/mL; range 0.0-20.7) experience an AE. No difference was observed in the rate of AEs between patients in mono- or combination therapy ( = .38), as well as between elderly (i.e., >65 years) and younger patients ( = .32). Considering a TL cutoff of 7 mcg/mL for infliximab and 12 mcg/mL for adalimumab, or even double these TL values, we observed no statistically significant difference in the rate of AEs occurrence. Our study suggests that, when clinically required, anti-TNF drug dosage may be increased without particular concerns regarding the risk of AEs occurrence in IBD patients, even in patients on combination therapy and elderly ones.
接受抗TNF药物治疗的炎症性肠病（IBD）患者中，高达40%在治疗1年内失去反应，因此需要优化药物治疗。尽管较高的药物谷浓度（TLs）与持续的临床疗效相关，但人们担心它们可能与更高的不良事件（AE）风险相关。目的是评估IBD患者接受抗TNF药物治疗时药物TLs与AE发生之间是否存在可能的关联。我们回顾性研究了113例接受阿达木单抗或英夫利昔单抗治疗的IBD患者队列，其中27例接受免疫抑制剂联合治疗。使用均相迁移率变动分析测量TLs。在中位随访16个月（范围1 - 144个月）期间，我们观察到58例患者发生了103次AE。我们发现发生AE的患者（6.7 mcg/mL；范围0.0 - 36.2）与未发生AE的患者（7.7 mcg/mL；范围0.0 - 20.7）的中位TLs无统计学显著差异（P = 0.21）。单药治疗或联合治疗的患者之间的AE发生率无差异（P = 0.38），老年患者（即>65岁）和年轻患者之间也无差异（P = 0.32）。考虑到英夫利昔单抗的TL截止值为7 mcg/mL，阿达木单抗为12 mcg/mL，甚至将这些TL值加倍，我们观察到AE发生率无统计学显著差异。我们的研究表明，在临床需要时，抗TNF药物剂量可以增加，而无需特别担心IBD患者发生AE的风险，即使是联合治疗的患者和老年患者。
