Hwang Jiwon, Kim Hye-Mi, Jeong Hyemin, Lee Jaejoon, Ahn Joong Kyong, Koh Eun-Mi, Kang Eun-Suk, Cha Hoon-Suk
National Police Hospital, Department of Internal Medicine, Seoul, South Korea.
Samsung Biomedical Research Institute, Seoul, South Korea.
Rev Bras Reumatol Engl Ed. 2017 Jul-Aug;57(4):311-319. doi: 10.1016/j.rbre.2016.11.009. Epub 2016 Dec 23.
The development of anti-drug antibodies against tumor necrosis factor inhibitors is a likely explanation for the failure of TNF-inhibitors in patients with spondyloarthritis. Our study determined the existence and clinical implications of ADAbs in axial spondyloarthritis patients.
According to the Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis, patients treated with adalimumab or infliximab were recruited consecutively. Serum samples were collected at enrollment to measure anti-drug antibodies and drug levels.
Of 100 patients, the mean duration of current TNF inhibitor use was 22.3±17.9 months. Anti-drug antibodies were detected in 5 of 72 adalimumab users compared to 5 of 28 infliximab users (6.9% vs. 17.9%). Anti-drug antibodies-positive patients had a significantly higher body mass index than anti-drug antibodies-negative patients among both adalimumab (28.4±5.9kg/m vs. 24.3±2.9kg/m, respectively, p=0.01) and infliximab users (25.9±2.8kg/m vs. 22.6±2.8kg/m, respectively, p=0.02). During the median 15-month follow-up period, drug discontinuation occurred more frequently in the anti-drug antibodies-positive group than the anti-drug antibodies-negative group (30.0% vs. 6.5%, respectively, p=0.04). In logistic regression, anti-drug antibodies positivity (OR=5.85, 95% CI 1.19-28.61, p=0.029) and body mass index (OR=4.35, 95% CI 1.01-18.69, p=0.048) were associated with a greater risk of stopping TNF inhibitor treatment.
Our result suggests that the presence of anti-drug antibodies against adalimumab and infliximab as well as a higher body mass index can predict subsequent drug discontinuation in axial spondyloarthritis patients.
抗肿瘤坏死因子抑制剂的抗药抗体产生可能是强直性脊柱炎患者使用肿瘤坏死因子抑制剂治疗失败的原因。我们的研究确定了强直性脊柱炎患者中抗药抗体的存在情况及其临床意义。
根据国际脊柱关节炎评估协会强直性脊柱炎分类标准，连续招募接受阿达木单抗或英夫利昔单抗治疗的患者。在入组时采集血清样本，检测抗药抗体和药物水平。
100例患者中，当前使用肿瘤坏死因子抑制剂的平均时长为22.3±17.9个月。72例使用阿达木单抗的患者中有5例检测出抗药抗体，而28例使用英夫利昔单抗的患者中有5例检测出抗药抗体（6.9%对17.9%）。在使用阿达木单抗的患者（分别为28.4±5.9kg/m²对24.3±2.9kg/m²，p=0.01）和使用英夫利昔单抗的患者（分别为25.9±2.8kg/m²对22.6±2.8kg/m²，p=0.02）中，抗药抗体阳性患者的体重指数均显著高于抗药抗体阴性患者。在中位15个月的随访期内，抗药抗体阳性组的药物停用发生率高于抗药抗体阴性组（分别为30.0%对6.5%，p=0.04）。在逻辑回归分析中，抗药抗体阳性（比值比=5.85，95%置信区间1.19 - 28.61，p=0.029）和体重指数（比值比=4.35，95%置信区间1.01 - 18. .69，p=0.048）与停止肿瘤坏死因子抑制剂治疗的风险增加相关。
我们的结果表明，抗阿达木单抗和英夫利昔单抗的抗药抗体的存在以及较高的体重指数可预测强直性脊柱炎患者后续的药物停用情况。
