Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain.
Laboratory Department, Hospital Marina Baixa, Villajoyosa, Alicante, Spain.
Rheumatol Int. 2019 May;39(5):841-849. doi: 10.1007/s00296-019-04288-7. Epub 2019 Mar 21.
Our aim was to assess the relationship between serum adalimumab levels, anti-drug antibodies (ADA) and disease activity in patients with axial spondylarthritis (SpA). We have carried out a single-centre cross-sectional study. adalimumab and ADA levels were analysed with ELISA and correlated with SpA activity using BASDAI and ASDAS scores. Adalimumab cut-off value was calculated to discriminate inactive disease/low disease activity (BASDAI < 4; ASDAS < 2.1) from moderate/high disease activity (BASDAI ≥ 4; ASDAS ≥ 2.1), using a receiver operating characteristic (ROC) curve. Up to January 2016, 51 consecutive patients were included. The median (range) age was 46.6 (18-68) and 47.1% were women. ADA prevalence was 27.5%, with none detected in the 21.6% receiving concomitant disease-modifying antirheumatic drugs (DMARDs) (p = 0.021). Adalimumab level was normal (> 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic adalimumab levels (< 3 mg/l), with ADA in 14 (93%). Median adalimumab (mg/l) was significantly higher in patients with inactive disease/low disease activity: BASDAI < 4 vs ≥ 4: 9.5 vs 2.6 (p < 0.01); ASDAS-CRP < 2.1 vs ≥ 2.1: 9.3 vs 0.3 (p < 0.001); ASDAS-ESR < 2.1 vs ≥ 2.1: 9.9 vs 3.0 (p < 0.001), and this finding was consistent with the result of the multivariate model. Patients with inactive disease/low disease activity presented significantly lower ADA levels. The adalimumab level cut-offs and area under the curve (AUC) obtained in the ROC curves were: ASDAS-CRP (< 2.1) 4.6 mg/l (AUC 81.2%; 95% CI 67.5-94.9; p < 0.001); ASDAS-ESR (< 2.1) 7.7 mg/l (AUC 82.4%; 95% CI 69.3-95.5; p < 0.001); BASDAI (< 4) 6.4 mg/l (AUC 73.5%; 95% CI 58.6-88.3; p < 0.01). In conclusion, presence of ADA in axial SpA patients treated with adalimumab was associated with lower serum drug levels. ADA levels were lower and adalimumab levels were higher in patients with inactive disease/low disease activity based on BASDAI and ASDAS indices. Concomitant treatment with MTX reduces de likelihood of finding ADA. Serum adalimumab levels above 4.6 mg/l are recommended to avoid compromising efficacy.
我们的目的是评估强直性脊柱炎（SpA）患者血清阿达木单抗水平、抗药物抗体（ADA）与疾病活动度之间的关系。我们进行了一项单中心横断面研究。采用 ELISA 法分析阿达木单抗和 ADA 水平，并采用 BASDAI 和 ASDAS 评分评估 SpA 活动度。采用受试者工作特征（ROC）曲线计算阿达木单抗截断值，以区分疾病不活动/低疾病活动（BASDAI<4；ASDAS<2.1）与中/高疾病活动（BASDAI≥4；ASDAS≥2.1）。截至 2016 年 1 月，共纳入 51 例连续患者。中位（范围）年龄为 46.6（18-68）岁，47.1%为女性。ADA 患病率为 27.5%，接受联合改善病情抗风湿药物（DMARDs）治疗的患者中未检出 ADA（21.6%，p=0.021）。36 例（70.6%）患者阿达木单抗水平正常（>3mg/l），均未检出 ADA。15 例（29.4%）患者阿达木单抗水平较低（<3mg/l），其中 14 例（93%）检出 ADA。疾病不活动/低疾病活动患者的阿达木单抗中位（mg/l）显著较高：BASDAI<4 比≥4：9.5 比 2.6（p<0.01）；ASDAS-CRP<2.1 比≥2.1：9.3 比 0.3（p<0.001）；ASDAS-ESR<2.1 比≥2.1：9.9 比 3.0（p<0.001），且这一结果与多变量模型一致。疾病不活动/低疾病活动患者的 ADA 水平显著较低。ROC 曲线获得的阿达木单抗水平截断值和曲线下面积（AUC）为：ASDAS-CRP（<2.1）4.6mg/l（AUC 81.2%；95%CI 67.5-94.9；p<0.001）；ASDAS-ESR（<2.1）7.7mg/l（AUC 82.4%；95%CI 69.3-95.5；p<0.001）；BASDAI（<4）6.4mg/l（AUC 73.5%；95%CI 58.6-88.3；p<0.01）。总之，接受阿达木单抗治疗的强直性脊柱炎患者 ADA 的存在与血清药物水平较低有关。基于 BASDAI 和 ASDAS 指标，疾病不活动/低疾病活动患者的 ADA 水平较低，阿达木单抗水平较高。同时接受 MTX 治疗可降低 ADA 检出率。建议阿达木单抗血清水平超过 4.6mg/l 以避免疗效受损。
