Scott Frank I, Lichtenstein Gary R
Crohn's and Colitis Center, Division of Gastroenterology, University of Colorado School of Medicine, 12605 E. 16th Ave., Aurora, CO, 80045, USA.
Center for IBD, Perelman Center for Advanced Medicine, Perelman School of Medicine of the University of Pennsylvania, One Convention Avenue, 7- South, Room 753, Philadelphia, PA, 19104, USA.
Curr Treat Options Gastroenterol. 2016 Mar;14(1):91-102. doi: 10.1007/s11938-016-0085-z.
Monoclonal antibody therapy directed against tumor necrosis factor-alpha (anti-TNFs) has revolutionized the care of patients with Crohn's disease and ulcerative colitis. These large proteins are potentially immunogenic. Early clinical trials demonstrated an association with both serum concentrations of these agents as well as the presence of antidrug antibodies generated by the host with loss of response. More recent research has provided further evidence to confirm the impact of low drug trough concentrations and antidrug antibodies on subsequent clinical course in CD and UC. Given these clinical implications, treatment algorithms have been developed to aid clinicians in interpreting trough drug levels and antibody concentrations in those with confirmed active disease. Several studies have demonstrated the utility of these approaches. Furthermore, there are growing data supporting the use of therapeutic drug monitoring in a prospective fashion in those patients who are clinically stable on anti-TNF therapies to ensure they are receiving appropriate dosing and have not yet developed antibodies. In addition, for those who have developed low-level antibodies, increasing the dose of an anti-TNF or adding an immunomodulator may help to overcome this immunologic response. Further research is required to assess these proposed strategies, as well as to determine the role of trough drug level assessment and antibody testing for new anti-TNFs and biologic medication with alternative mechanisms of action.
针对肿瘤坏死因子-α的单克隆抗体疗法（抗TNFs）彻底改变了克罗恩病和溃疡性结肠炎患者的治疗方式。这些大分子蛋白质具有潜在的免疫原性。早期临床试验表明，这些药物的血清浓度以及宿主产生的抗药抗体与疗效丧失之间存在关联。最近的研究提供了进一步的证据，证实低药物谷浓度和抗药抗体对克罗恩病和溃疡性结肠炎后续临床病程的影响。鉴于这些临床意义，已制定治疗算法，以帮助临床医生解读确诊为活动性疾病患者的药物谷浓度和抗体浓度。多项研究证明了这些方法的实用性。此外，越来越多的数据支持在接受抗TNF治疗且临床稳定的患者中前瞻性地使用治疗药物监测，以确保他们接受适当剂量的药物且尚未产生抗体。此外，对于已产生低水平抗体的患者，增加抗TNF剂量或添加免疫调节剂可能有助于克服这种免疫反应。需要进一步研究来评估这些提议的策略，以及确定药物谷浓度评估和抗体检测对于新的抗TNF药物以及具有替代作用机制的生物药物的作用。
