M. Bredemeier, MD, PhD, Hospital Nossa Senhora da Conceição, Grupo Hospitalar Conceição, Porto Alegre;
R. Ranza, MD, PhD, Universidade Federal de Uberlândia, Uberlândia.
J Rheumatol. 2021 Oct;48(10):1519-1527. doi: 10.3899/jrheum.201248. Epub 2021 May 1.
To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors (JAKi).
Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons.
In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76-1.31, = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36-0.88, = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25-0.94, = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16-0.65, = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis.
In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.
评估甲氨蝶呤（MTX）-来氟米特（LEF）联合方案在类风湿关节炎（RA）中的安全性，并与其他涉及传统合成（cs-）和生物（b-）疾病修饰抗风湿药物（DMARDs）或 Janus 激酶抑制剂（JAKi）的治疗方案进行比较。
在巴西的一项基于注册的、多中心队列研究（BiobadaBrasil）中，随访开始接受 csDMARD（无先前使用 bDMARD 或 JAKi）治疗或首次接受 bDMARD/JAKi 治疗的 RA 患者。主要结局是严重不良事件（SAEs）的发生率；次要结局包括严重感染。采用多变量 Cox 比例风险模型和倾向评分匹配分析（PSMA）进行统计比较。
共纳入 1671 例患者（5349 患者年[PY]）；452 例患者（1537 PY）接受 MTX+LEF 治疗。SAEs 的总发生率为 5.6/100 PY。MTX+LEF 的 SAE 风险并不高于 MTX 或 LEF（调整后的 HR[aHR]1.00，95%CI0.76-1.31， = 0.98）。MTX+LEF 的 SAE（aHR0.56，95%CI0.36-0.88， = 0.01）和感染性 SAE（aHR0.48，95%CI0.25-0.94， = 0.03）风险低于 MTX+LEF 联合 bDMARDs/JAKi。MTX+LEF 的 SAE 风险低于 MTX+柳氮磺胺吡啶（SSZ；aHR0.33，95%CI0.16-0.65， = 0.002）。采用 PSMA 的分析结果与传统多变量 Cox 分析结果一致。
在本研究中，与 MTX+SSZ 和涉及 RA 中高级治疗的方案相比，MTX+LEF 的总体安全性相对较好。
