Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
RMD Open. 2024 Nov 13;10(4):e004888. doi: 10.1136/rmdopen-2024-004888.
The objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis.
Associations between serum adalimumab trough levels and disease activity were examined using longitudinal data from a 48-week randomised phase III trial including patients with tumour necrosis factor inhibitor-naïve rheumatoid arthritis with active disease starting adalimumab treatment. Disease activity was classified according to 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate and C reactive protein (CRP) levels.
Adalimumab trough levels were recorded longitudinally for 336, 330 and 302 patients at weeks 12, 24 and 48, respectively. All patients received concomitant methotrexate. Median adalimumab trough levels were 6.4 mg/L (IQR 3.4-9.5) at week 12, 7.5 mg/L (IQR 3.5-10.9) at week 24 and 7.6 mg/L (IQR 3.6-12.0) at week 48. In serial serum samples from weeks 12, 24 and 48, trough levels ≥3.9 mg/L were associated with DAS28 remission (OR 3.88 (95% CI 1.80, 8.38), p<0.001) and lower CRP levels (p<0.001). Week 12 trough levels ≥3.5 mg/L were associated with DAS28 low disease activity at week 24 (OR 2.62 (1.50, 4.56), p<0.001) and remission at week 48 (OR 1.99 (1.02, 3.88), p=0.04), as well as lower CRP levels at both time points (p<0.001).
Adalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy and can be considered a lower target level for therapeutic drug monitoring of adalimumab therapy.
本研究旨在确定与类风湿关节炎患者缓解和低疾病活动度相关的阿达木单抗治疗血清水平。
采用来自一项 48 周随机 III 期试验的纵向数据，纳入初治肿瘤坏死因子抑制剂的类风湿关节炎患者，这些患者在开始阿达木单抗治疗时疾病处于活动期。根据 28 关节疾病活动评分（DAS28）-红细胞沉降率和 C 反应蛋白（CRP）水平来对疾病活动度进行分类。
分别在第 12、24 和 48 周时对 336、330 和 302 例患者进行了阿达木单抗谷浓度的纵向记录。所有患者均接受了甲氨蝶呤联合治疗。中位阿达木单抗谷浓度分别为第 12 周时 6.4mg/L（IQR 3.4-9.5）、第 24 周时 7.5mg/L（IQR 3.5-10.9）和第 48 周时 7.6mg/L（IQR 3.6-12.0）。在第 12、24 和 48 周的连续血清样本中，谷浓度≥3.9mg/L 与 DAS28 缓解（OR 3.88（95%CI 1.80，8.38），p<0.001）和较低的 CRP 水平相关（p<0.001）。第 12 周时谷浓度≥3.5mg/L 与第 24 周的 DAS28 低疾病活动度（OR 2.62（1.50，4.56），p<0.001）和第 48 周的缓解相关（OR 1.99（1.02，3.88），p=0.04），同时也与两个时间点的 CRP 水平降低相关（p<0.001）。
阿达木单抗谷浓度超过 4.0mg/L 与阿达木单抗治疗的第一年的缓解/低疾病活动度相关，可作为阿达木单抗治疗的治疗药物监测的较低目标水平。
