Marits Per, Landucci Laura, Sundin Ulf, Davidsdottir Loa, Nilsson Jakob, Befrits Ragnar, Wikström Ann-Charlotte, Eberhardson Michael
Dept of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Dept of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
J Crohns Colitis. 2014 Aug;8(8):881-9. doi: 10.1016/j.crohns.2014.01.009. Epub 2014 Jan 31.
The anti-TNF antibody infliximab is effective in inducing remission in Crohn's disease as well as in ulcerative colitis and many patients are treated for several years with sustained clinical remission. However, the role of monitoring s-infliximab and antibodies towards infliximab during maintenance treatment remains unclear. Our aim was to correlate serum drug levels and antibodies to clinical activity, CRP, albumin and concomitant immunosuppression in a cohort on maintenance infliximab treatment.
We included 79 patients with Crohn's disease or ulcerative colitis who had responded to infliximab and received maintenance treatment (4-69 infusions) in this retrospective study. Infliximab levels and antibodies towards the drug were analyzed with in-house-developed ELISA assays.
The mean s-infliximab was significantly higher in patients in remission (4.1μg/mL) as compared with disease flare (mean 1.8μg/mL); p<0.001. The s-infliximab showed a significant negative correlation with Harvey-Bradshaw index (r=-0.21; p<0.05). Serum-infliximab progressively decreased with the number of accumulated infusions (p<0.05). In patients with undetectable trough levels, 55% of the patients with concomitant immunosuppressive were positive for antibodies against infliximab, as compared with 94% of patients on monotherapy. Patients with undetectable serum-infliximab were in clinical remission at 25% of the visits.
The trough level 4.1μg/mL may serve as cut-off for clinical remission. Drug trough levels decreased during treatment and almost all patients with undetectable s-infliximab and monotherapy had developed antibodies against the drug.
抗TNF抗体英夫利昔单抗在诱导克罗恩病及溃疡性结肠炎缓解方面有效，许多患者接受数年治疗后可维持临床缓解。然而，在维持治疗期间监测可溶性英夫利昔单抗（s - infliximab）及抗英夫利昔单抗抗体的作用仍不明确。我们的目的是在一组接受英夫利昔单抗维持治疗的患者中，将血清药物水平及抗体与临床活动度、CRP、白蛋白及同时使用的免疫抑制治疗进行关联分析。
在这项回顾性研究中，我们纳入了79例对英夫利昔单抗有反应并接受维持治疗（4 - 69次输注）的克罗恩病或溃疡性结肠炎患者。采用自行研发的ELISA检测法分析英夫利昔单抗水平及抗该药物的抗体。
缓解期患者的平均s - 英夫利昔单抗水平（4.1μg/mL）显著高于疾病发作期（平均1.8μg/mL）；p < 0.001。s - 英夫利昔单抗与哈维 - 布拉德肖指数呈显著负相关（r = - 0.21；p < 0.05）。血清英夫利昔单抗水平随累积输注次数逐渐降低（p < 0.05）。在谷浓度检测不到的患者中，同时接受免疫抑制治疗的患者有55%抗英夫利昔单抗抗体呈阳性，而单药治疗患者中这一比例为94%。血清英夫利昔单抗检测不到的患者在25%的就诊时处于临床缓解状态。
谷浓度4.1μg/mL可作为临床缓解的临界值。治疗期间药物谷浓度降低，几乎所有血清英夫利昔单抗检测不到且接受单药治疗的患者都产生了抗该药物的抗体。
