Gastroenterology Departments of: Hospital Universitario de Fuenlabrada and Instituto de Investigación La Princesa (IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD). Madrid. Spain.
Curr Drug Metab. 2011 Jul;12(6):594-8. doi: 10.2174/138920011795713689.
Tumor necrosis factor alpha (TNFα) is a cytokine with a critical role in the pathogenesis of some chronic inflammatory diseases, such as inflammatory bowel diseases. Anti-TNF agents, which neutralize the biological activity of TNFα, are widely used among the different therapeutic options for the treatment of patients with inflammatory bowel diseases. These drugs are very useful in clinical practice, but some patients experience lack and loss of response during the treatment. Drug serum concentration, antibodies against anti-TNF agents, clearance of the drug, formation of immune complexes, a more severe disease and probably other unknown factors can influence the treatment's efficacy. Nowadays, the management of patients with lack or loss of response is empirical. The measurement of drug concentrations and antibodies against anti-TNF agents might be useful for improving the selection of patients that will benefit from the maintenance treatment. In clinical practice, these methods may help us decide which strategy will be used in cases of loss of response: treatment intensification, shortening the infusion interval, increasing the dose, switching to another anti-TNF agent or to a drug with another mechanism of action. The optimal strategy in the future may be comprised of an early detection of loss of response to the treatment by assessing clinical symptoms and finding evidence of activity of the disease on endoscopic or radiological examinations when necessary, as well as a better management of anti-TNF treatment aided by measuring the serum concentration of the drug and antibodies against the drug.
肿瘤坏死因子-α(TNFα)是一种细胞因子,在某些慢性炎症性疾病(如炎症性肠病)的发病机制中起着关键作用。抗 TNF 药物可中和 TNFα 的生物学活性,是治疗炎症性肠病患者的多种治疗选择之一。这些药物在临床实践中非常有用,但有些患者在治疗过程中会出现缺乏和失去反应的情况。药物血清浓度、抗 TNF 药物的抗体、药物清除率、免疫复合物的形成、更严重的疾病以及可能存在的其他未知因素都可能影响治疗的疗效。如今,缺乏或失去反应的患者的管理是经验性的。药物浓度和抗 TNF 药物抗体的测量可能有助于改善对将从维持治疗中获益的患者的选择。在临床实践中,这些方法可以帮助我们决定在失去反应的情况下将使用哪种策略:治疗强化、缩短输注间隔、增加剂量、转换为另一种抗 TNF 药物或另一种具有不同作用机制的药物。未来的最佳策略可能包括通过评估临床症状和在必要时通过内镜或影像学检查发现疾病活动的证据来早期检测对治疗的缺乏或失去反应,以及通过测量药物血清浓度和抗药物抗体来更好地管理抗 TNF 治疗。