Department of Pharmacy Administration, College of Pharmacy, University of Mississippi, Oxford, MS, USA.
Section of Immunology, Allergy & Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Clin Rheumatol. 2024 Jan;43(1):103-116. doi: 10.1007/s10067-023-06709-2. Epub 2023 Aug 4.
This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA).
This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively.
In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54 [1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses.
The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.
本研究旨在探讨类风湿关节炎（RA）患者使用疾病修饰抗风湿药物（DMARDs）与心血管疾病（CVD）风险之间的相关性。
本巢式病例对照研究使用 MarketScan 数据库（2012-2014 年），纳入 2013 年 1 月 1 日至 2014 年 12 月 31 日期间起始使用传统合成型（cs）DMARD、生物型 DMARD 或靶向合成型（ts）DMARD 的成年 RA 患者（年龄≥18 岁），且无 CVD 病史。病例通过医疗索赔中的诊断代码或程序代码确定，采用事件密度抽样法（with replacement），以 1:10 的比例匹配年龄和性别，对每个病例选择 10 名对照。DMARD 处方测量时间为事件日期前 90 天。采用条件 logistic 回归分析，以甲氨蝶呤（MTX）单药治疗为参照，调整基线混杂因素，评估 CVD 风险与 DMARD 联合治疗或单独使用的相关性。分别对 DMARD 联合治疗组和 DMARD 单药治疗组进行亚组分析。
共纳入 270 例 CVD 事件病例和 2700 名对照（平均[标准差]年龄：54[1]；75.6%为女性）。最常见的处方 DMARD 治疗方案为 csDMARD 单药治疗（n=795，27.04%），其次是肿瘤坏死因子抑制剂（TNFi）单药治疗（n=367，12.48%）和 TNFi 联合 MTX 治疗（n=314，10.68%）。与 MTX 单药治疗相比，包括各种 DMARD 联合治疗方案在内，总体 DMARD 药物使用与 CVD 风险差异无关。亚组分析结果相似。
与 MTX 单药治疗相比，本研究发现 RA 患者使用 DMARD 联合治疗或单药治疗与 CVD 风险无差异。
关键点
· 本研究评估了类风湿关节炎（RA）患者使用疾病修饰抗风湿药物（DMARDs）与心血管疾病（CVD）风险之间的相关性。
· 结果表明，与 MTX 单药治疗相比，早期 RA 患者使用 DMARD 联合 MTX 或单独使用 DMARD 治疗与 CVD 风险无差异。
· 进一步的研究应侧重于更好地理解 DMARD 联合治疗与 MTX 联合治疗在改变 CV 风险方面的作用机制。
