Gehin J E, Warren D J, Syversen S W, Lie E, Sexton J, Loli L, Wierød A, Bjøro T, Kvien T K, Bolstad N, Goll G L
Department of Medical Biochemistry, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
Scand J Rheumatol. 2021 Nov;50(6):445-454. doi: 10.1080/03009742.2021.1875040. Epub 2021 Mar 2.
: This study aimed to identify the therapeutic target concentration and frequency of anti-drug antibodies (ADAbs) in golimumab-treated patients with inflammatory joint disease (IJD).: Associations between golimumab concentration, ADAbs, and treatment response were examined in 91 patients with IJD [41 axial spondyloarthritis (axSpA), 20 rheumatoid arthritis (RA), and 30 psoriatic arthritis (PsA)] included in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement in axSpA, European League Against Rheumatism (EULAR) good/moderate response in RA, and improvement of ≥ 50% in modified Disease Activity index for PSoriatic Arthritis (DAPSA) (28 swollen/tender joint counts) in PsA. Serum drug concentrations and ADAbs were analysed using automated in-house assays.: At inclusion, 42% were biological disease-modifying anti-rheumatic drug naïve and 42% used concomitant synthetic disease-modifying anti-rheumatic drug. The median golimumab concentration was 2.2 (interquartile range 1.0-3.5) mg/L. The proportions of responders after 3 months among patients with golimumab concentration < 1.0, 1.0-3.9, and ≥ 4.0 mg/L were 19%, 49%, and 74%, respectively. A higher rate of treatment discontinuation was seen in patients with serum golimumab concentration < 1.0 compared to ≥ 1.0 mg/L (hazard ratio 3.3, 95% confidence interval 1.8-6.0, p < 0.05). ADAbs were detected in 6%, and were associated with lower drug concentrations and both reduced treatment response and drug survival.: Golimumab concentrations ≥ 1.0 mg/L were associated with improved treatment response and better drug survival, although some patients may benefit from higher concentrations. This study suggests a rationale for dosing guided by therapeutic drug monitoring in golimumab-treated patients with IJD. The results should be confirmed in larger studies including trough samples, and the efficacy of such a strategy must be examined in randomized controlled trials.
本研究旨在确定接受戈利木单抗治疗的炎症性关节病（IJD）患者中抗药物抗体（ADAbs）的治疗目标浓度和频率。在NOR-DMARD研究纳入的91例IJD患者[41例轴向型脊柱关节炎（axSpA）、20例类风湿关节炎（RA）和30例银屑病关节炎（PsA）]中，研究了戈利木单抗浓度、ADAbs与治疗反应之间的关联。治疗反应根据强直性脊柱炎疾病活动评分（ASDAS）中axSpA的临床重要改善、欧洲抗风湿病联盟（EULAR）对RA的良好/中度反应以及银屑病关节炎改良疾病活动指数（DAPSA）（28个肿胀/压痛关节计数）中≥50%的改善来定义。血清药物浓度和ADAbs采用内部自动化检测方法进行分析。纳入时，42%的患者未使用过生物改善病情抗风湿药，42%的患者同时使用合成改善病情抗风湿药。戈利木单抗的中位浓度为2.2（四分位间距1.0 - 3.5）mg/L。戈利木单抗浓度<1.0、1.0 - 3.9和≥4.0 mg/L的患者在3个月后的缓解比例分别为19%、49%和74%。血清戈利木单抗浓度<1.0 mg/L的患者与≥1.0 mg/L的患者相比，治疗中断率更高（风险比3.3，95%置信区间1.8 - 6.0，p<0.05）。检测到6%的患者存在ADAbs，其与较低的药物浓度、降低的治疗反应和药物留存率相关。戈利木单抗浓度≥1.0 mg/L与改善的治疗反应和更好的药物留存率相关，尽管一些患者可能从更高浓度中获益。本研究为在接受戈利木单抗治疗的IJD患者中进行治疗药物监测指导给药提供了理论依据。研究结果应在包括谷值样本的更大规模研究中得到证实，并且必须在随机对照试验中检验这种策略的疗效。
