Steenholdt Casper, Bendtzen Klaus, Brynskov Jørn, Thomsen Ole Østergaard, Ainsworth Mark Andrew
Department of Medical Gastroenterology, University Hospital of Copenhagen, Herlev Hospital, Herlev, Denmark.
Scand J Gastroenterol. 2011 Mar;46(3):310-8. doi: 10.3109/00365521.2010.536254. Epub 2010 Nov 18.
Reasons for infliximab failure in Crohn's disease and ulcerative colitis are debated. Serum levels of infliximab and anti-infliximab antibodies have been associated with loss of response. We aimed at determining cut-off levels for infliximab and anti-infliximab antibody concentrations associated with clinical response to infliximab maintenance therapy.
Patients with inflammatory bowel disease (n = 106) were retrospectively classified as having maintained response or loss of response to infliximab maintenance therapy. Trough concentrations were measured by fluid-phase radioimmunoassays.
Infliximab levels were significantly lower, and anti-infliximab antibody levels significantly higher, in Crohn's disease patients with loss of response (median infliximab 0 μg/ml, median anti-infliximab antibodies 35 U/ml) compared to patients with maintained response (median infliximab 2.8 μg/ml, median anti-infliximab antibodies 0 U/ml; p < 0.0001). Receiver operating characteristic (ROC) analysis identified optimal cut-off values: infliximab <0.5 μg/ml, which was associated with loss of response with sensitivity 86% [64-97] and specificity 85% [72-94]; and anti-infliximab antibodies ≥10 U/ml yielding a sensitivity of 81% [61-93] and specificity 90% [79-96]. Combined measurements of infliximab and anti-infliximab antibodies using these cut-off values had higher accuracy yielding a sensitivity of 81% [57-94] and specificity 94% [82-98]. Similar pattern was observed in a smaller cohort of patients with ulcerative colitis.
Combined measurements of infliximab and anti-infliximab antibodies using cut-off levels provided high accuracy for discriminating between clinical response types to infliximab maintenance therapy. Cut-off levels are considered a prerequisite to further investigations of clinical usefulness of measurements of infliximab and anti-infliximab antibodies in patients failing infliximab therapy.
英夫利昔单抗治疗克罗恩病和溃疡性结肠炎失败的原因存在争议。英夫利昔单抗血清水平及抗英夫利昔单抗抗体与疗效丧失有关。我们旨在确定与英夫利昔单抗维持治疗临床反应相关的英夫利昔单抗和抗英夫利昔单抗抗体浓度的临界值。
对106例炎症性肠病患者进行回顾性分类，分为对英夫利昔单抗维持治疗有持续反应或反应丧失两类。采用液相放射免疫分析法测定谷浓度。
与有持续反应的患者（英夫利昔单抗中位数2.8μg/ml，抗英夫利昔单抗抗体中位数0 U/ml；p<0.0001）相比，反应丧失的克罗恩病患者英夫利昔单抗水平显著降低，抗英夫利昔单抗抗体水平显著升高（英夫利昔单抗中位数0μg/ml，抗英夫利昔单抗抗体中位数35 U/ml）。受试者工作特征（ROC）分析确定了最佳临界值：英夫利昔单抗<0.5μg/ml，与反应丧失相关，敏感性为86%[64-97]，特异性为85%[72-94]；抗英夫利昔单抗抗体≥10 U/ml，敏感性为81%[61-93]，特异性为90%[79-96]。使用这些临界值联合检测英夫利昔单抗和抗英夫利昔单抗抗体具有更高的准确性，敏感性为81%[57-94]，特异性为94%[82-98]。在一小群溃疡性结肠炎患者中观察到类似模式。
使用临界值联合检测英夫利昔单抗和抗英夫利昔单抗抗体，对于区分英夫利昔单抗维持治疗的临床反应类型具有较高的准确性。临界值被认为是进一步研究英夫利昔单抗治疗失败患者中英夫利昔单抗和抗英夫利昔单抗抗体检测临床实用性的先决条件。
