Objective High adalimumab serum concentrations do not result in better response in patients with rheumatoid arthritis (RA), suggesting overexposure. We investigated whether patients with adalimumab concentrations >8 µg/mL can prolong their dosing interval by 50% without a clinically relevant change in disease activity. Methods Consecutive patients with RA, treated with adalimumab 40 mg every other week for at least 28 weeks, were approached for this randomised, open-label, non-inferiority trial. Patients with adalimumab trough concentrations >8 µg/mL were randomly (1:1) assigned to dose-interval prolongation of once every 3 weeks or continuation of every other week. Primary outcome was the change in disease activity score of 28 joints (ΔDAS28-ESR) after 28 weeks, with a non-inferiority margin of 0.6 points. Results In total, 147 patients were screened. Fifty-five patients had concentrations >8 µg/mL and were randomised. Mean ΔDAS28 after 28 weeks was –0.14±SD 0.61 in the prolongation group and 0.30±0.52 in the continuation group. Mean difference was significantly in favour of the prolongation group: 0.44 (95% CI 0.12 to 0.76, p=0.01). Conclusions Adalimumab-treated patients with RA with trough concentrations >8 µg/mL can prolong their standard dosing interval to once every 3 weeks without loss of disease control. Trial registration number NTR3509; Results.

中文翻译：

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成功减少血清阿达木单抗高浓度类风湿性关节炎患者的过度暴露：一项开放标签、非劣效性、随机临床试验

目的 高阿达木单抗血清浓度不会导致类风湿性关节炎 (RA) 患者更好的反应，表明过度暴露。我们调查了阿达木单抗浓度 >8 µg/mL 的患者是否可以将他们的给药间隔延长 50%，而疾病活动没有临床相关的变化。方法 连续的 RA 患者，每隔一周接受 40 mg 阿达木单抗治疗至少 28 周，参与这项随机、开放标签、非劣效性试验。阿达木单抗谷浓度 >8 µg/mL 的患者被随机 (1:1) 分配到每 3 周一次的剂量间隔延长或每两周一次的延续。主要结果是 28 周后 28 个关节的疾病活动评分（ΔDAS28-ESR）的变化，非劣效性边际为 0.6 分。结果 总共，筛选了 147 名患者。55 名患者的浓度 >8 µg/mL 并被随机分组​​。28 周后的平均 ΔDAS28 在延长组中为 –0.14±SD 0.61，在继续组中为 0.30±0.52。平均差异显着有利于延长组：0.44（95% CI 0.12 至 0.76，p=0.01）。结论阿达木单抗治疗的 RA 患者的谷浓度 >8 µg/mL 可以将其标准给药间隔延长至每 3 周一次，而不会失去疾病控制。试用注册号NTR3509；结果。结论阿达木单抗治疗的 RA 患者的谷浓度 >8 µg/mL 可以将其标准给药间隔延长至每 3 周一次，而不会失去疾病控制。试用注册号NTR3509；结果。结论阿达木单抗治疗的 RA 患者的谷浓度 >8 µg/mL 可以将其标准给药间隔延长至每 3 周一次，而不会失去疾病控制。试用注册号NTR3509；结果。