儿童非系统性幼年特发性关节炎患者初始生物治疗时间相关因素的处方模式及影响。

Prescribing Patterns and Impact of Factors Associated with Time to Initial Biologic Therapy among Children with Non-systemic Juvenile Idiopathic Arthritis.

机构信息

Division of Pharmacy Practice and Administrative Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 3225 Eden Ave., Cincinnati, OH, 45267, USA.

Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

出版信息

Paediatr Drugs. 2021 Mar;23(2):171-182. doi: 10.1007/s40272-021-00436-4. Epub 2021 Mar 2.

DOI:10.1007/s40272-021-00436-4

PMID:33651370

Abstract

OBJECTIVE

The aim of this study was to examine patterns of initial prescriptions, investigate time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs), and evaluate the impact of clinical and other baseline factors associated with the time to first bDMARD in treating children with newly diagnosed non-systemic juvenile idiopathic arthritis (JIA).

METHODS

Using longitudinal patient-level data extracted from electronic medical records (EMR) in a large Midwestern pediatric hospital from 2009 to 2018, the initial prescriptions and prescribing patterns of bDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids within 3 months of JIA diagnosis were examined. Kaplan-Meier analyses were performed to assess time to initiation of bDMARDs. Cox proportional hazard models were used to identify factors associated with time to first bDMARD.

RESULTS

Of 821 children, the proportion of patients with initial csDMARDs increased from 45.3% in 2009 to 60.3% in 2018. Around 57.5% of polyarthritis rheumatoid factor-positive (Poly RF+) patients and 43.2% of polyarthritis rheumatoid factor-negative (Poly RF-) patients received a bDMARD therapy within 3 months of diagnosis, 14.4% as monotherapy and 28.3% in combination with a csDMARD. Among patients who received combination therapy, combination of methotrexate with adalimumab increased from 16.7% in 2009 to 40% in 2018. The proportion of patients treated with adalimumab gradually increased and passed etanercept in 2016. The predictors of earlier initiation of biologic therapy were JIA category enthesitis-related arthritis (ERA) [hazard ratio (HR) vs persistent oligoarthritis 4.82; p < 0.0001], psoriatic arthritis (PsA) (HR 2.46; p = 0.0002), or Poly RF- (HR 2.43; p = 0.0002); the number of joints with limited range of motion (HR 1.02; p = 0.0222), and erythrocyte sedimentation rate (ESR, HR 1.01; p = 0.0033).

CONCLUSIONS

There was a substantial increase in the proportion of patients receiving the combination of methotrexate and adalimumab among patients receiving combination therapy. Adalimumab overtook etanercept as the most frequently prescribed bDMARD. Multiple factors affect the time to biologic initiation, including the number of joints with limited range of motion, ESR, and JIA category.

摘要

目的

本研究旨在分析新诊断的儿童幼年特发性关节炎（JIA）患者的初始处方模式，探究生物改善病情抗风湿药物（bDMARD）的起始时间，并评估与首次 bDMARD 时间相关的临床和其他基线因素。

方法

本研究使用了来自一家中西部大型儿科医院的电子病历（EMR）中的纵向患者水平数据，对 2009 年至 2018 年 JIA 诊断后 3 个月内的 bDMARD、传统合成改善病情抗风湿药物（csDMARD）、非甾体抗炎药（NSAIDs）和糖皮质激素的初始处方和处方模式进行了分析。采用 Kaplan-Meier 分析评估 bDMARD 的起始时间。采用 Cox 比例风险模型确定与首次 bDMARD 时间相关的因素。

结果

在 821 名儿童中，初始 csDMARD 治疗的比例从 2009 年的 45.3%增加到 2018 年的 60.3%。约 57.5%的多关节炎类风湿因子阳性（Poly RF+）患者和 43.2%的多关节炎类风湿因子阴性（Poly RF-）患者在诊断后 3 个月内接受了 bDMARD 治疗，其中 14.4%为单药治疗，28.3%为联合 csDMARD 治疗。在接受联合治疗的患者中，甲氨蝶呤联合阿达木单抗的比例从 2009 年的 16.7%增加到 2018 年的 40%。阿达木单抗的治疗比例逐渐增加，并于 2016 年超过依那西普。生物治疗起始时间更早的预测因素包括幼年特发性关节炎类别附着点相关关节炎（ERA）[风险比（HR）vs 持续性少关节炎 4.82；p<0.0001]、银屑病关节炎（PsA）（HR 2.46；p=0.0002）或 Poly RF-（HR 2.43；p=0.0002）；活动受限关节数（HR 1.02；p=0.0222）和红细胞沉降率（ESR，HR 1.01；p=0.0033）。