Centre for Rheumatology, Division of Medicine, University College London, London, UK and Rayne Institute, 5 University St, Bloomsbury, London WC1E 6JF.
Comprehensive Clinical Trials Unit, University College London, Institute of Clinical Trials & Methodology, Faculty of Population Health Sciences, 90 High Holborn, Holborn, London WC1V 6LJ.
Rheumatology (Oxford). 2022 Feb 2;61(2):787-793. doi: 10.1093/rheumatology/keab403.
To determine whether concomitant HCQ modulates the increase in erythrocyte mean corpuscular volume (MCV) caused by MTX therapy, and whether this is associated with improved clinical response in RA.
A retrospective observational analysis was conducted on two independent hospital datasets of biologic-naïve, early-RA patients who started oral MTX. Baseline characteristics, DAS28-ESR and monthly MCV after starting MTX were obtained. Conventional and machine-learning statistical approaches were applied to the discovery cohort (Cohort 1, 655 patients) and results validated using Cohort 2 (225 patients).
HCQ therapy with MTX was associated with a 2-fold increase in the likelihood of response defined in this study as clinical remission or low disease activity at 6 months (P <0.001). The improved clinical outcome of combination HCQ and MTX therapy was associated with an accelerated rise in MCV from 2 months after commencing therapy. The increase in MCV at 3 months was equivalent to the contemporaneous reduction in the DAS (DAS28-ESR) in predicting clinical response at 6 months. Using latent class mixed modelling, five trajectories of MCV change over 6 months from baseline were identified. The odds ratio of response to treatment was 16.2 (95% CI 5.7, 46.4, P <0.001) in those receiving combination therapy classified within the MCV elevation >5 fl class, which contained the most patients, compared with MTX alone.
Our data provide mechanistic insight into the synergistic clinical benefit of concomitant HCQ with MTX, boosting the rise in MCV, which could serve as a companion biomarker of treatment response.
确定羟氯喹（HCQ）是否会调节甲氨蝶呤（MTX）治疗引起的红细胞平均体积（MCV）升高，并确定其是否与 RA 患者的临床改善相关。
对开始接受口服 MTX 的生物制剂初治早期 RA 患者的两个独立医院数据集进行回顾性观察分析。获得基线特征、DAS28-ESR 和开始 MTX 后每月的 MCV。采用传统和机器学习统计方法对发现队列（队列 1，655 例患者）进行分析，并使用队列 2（225 例患者）进行验证。
MTX 联合 HCQ 治疗与本研究定义的应答（6 个月时临床缓解或疾病低度活动）的可能性增加 2 倍相关（P＜0.001）。HCQ 联合 MTX 治疗改善的临床结局与治疗开始后 2 个月 MCV 的快速升高相关。3 个月时 MCV 的增加与同时期 DAS（DAS28-ESR）的降低在预测 6 个月时的临床应答方面具有同等作用。采用潜在类别混合模型，从基线到 6 个月时共确定了 5 种 MCV 变化轨迹。与单独接受 MTX 治疗相比，MCV 升高＞5 fl 类别的联合治疗患者的治疗应答比值比为 16.2（95%CI 5.7，46.4，P＜0.001）。
我们的数据为 MTX 联合 HCQ 的协同临床获益提供了机制上的见解，增强了 MCV 的升高，这可能成为治疗应答的伴随生物标志物。
