Arad Uri, Elkayam Ori
From the Department of Rheumatology, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
U. Arad, MD, PhD, Consultant Rheumatologist, Lecturer, Department of Rheumatology, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University; O. Elkayam, MD, Head of Department of Rheumatology, Associate Professor, Department of Rheumatology, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University.
J Rheumatol. 2019 Dec;46(12):1577-1581. doi: 10.3899/jrheum.181431. Epub 2019 Jun 1.
To determine whether serum trough concentrations of tocilizumab (TCZ) administered as a fixed-dose subcutaneous (SC) injection for the treatment of rheumatoid arthritis (RA) are associated with disease activity responses.
We analyzed datasets from the Israeli branch of the multinational TOZURA study, which evaluated a weekly subcutaneous TCZ treatment regimen in a real-life clinical setting. Generalized estimating equations (GEE) were used to evaluate associations between the TCZ levels and the study outcomes. Linear models and GEE were used to evaluate associations between patient characteristics and TCZ levels.
A significant association between the TCZ concentrations and the change in the Clinical Disease Activity Index (CDAI) score was observed. In a multivariate binary GEE model, every increase of 10 µg/ml in the concentration of TCZ was associated with being in a state of CDAI remission or low disease activity (OR 1.41) versus a moderate/high disease activity state. An OR of 1.52 was associated with being in a state of Health Assessment Questionnaire-Disability Index remission. In univariate linear models, there was an inverse association between body mass index (BMI) and improvement in the CDAI score, and the BMI score was associated with lower TCZ concentrations. Patients who weighed > 100 kg had lower TCZ concentrations.
In the first 24 weeks of treatment with SC TCZ injections, TCZ concentrations were associated with clinical improvement, while body weight and BMI were inversely associated with TCZ concentrations. Personalizing the dose of SC TCZ to body weight may improve outcomes of clinical disease activity in patients with RA.
确定作为固定剂量皮下注射给药用于治疗类风湿关节炎（RA）的托珠单抗（TCZ）血清谷浓度是否与疾病活动反应相关。
我们分析了多国TOZURA研究以色列分支的数据集，该研究在现实临床环境中评估了每周皮下注射TCZ的治疗方案。使用广义估计方程（GEE）评估TCZ水平与研究结果之间的关联。使用线性模型和GEE评估患者特征与TCZ水平之间的关联。
观察到TCZ浓度与临床疾病活动指数（CDAI）评分变化之间存在显著关联。在多变量二元GEE模型中，TCZ浓度每增加10μg/ml，与处于CDAI缓解或低疾病活动状态（比值比[OR]为1.41）而非中度/高度疾病活动状态相关。OR为1.52与处于健康评估问卷 - 残疾指数缓解状态相关。在单变量线性模型中，体重指数（BMI）与CDAI评分改善之间存在负相关，且BMI评分与较低的TCZ浓度相关。体重>100kg的患者TCZ浓度较低。
在皮下注射TCZ治疗的前24周，TCZ浓度与临床改善相关，而体重和BMI与TCZ浓度呈负相关。根据体重个性化皮下注射TCZ的剂量可能会改善RA患者临床疾病活动的结果。
