Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
Department of Rheumatology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh.
Int J Rheum Dis. 2023 Sep;26(9):1729-1736. doi: 10.1111/1756-185X.14801. Epub 2023 Jun 28.
To compare tofacitinib and methotrexate (MTX) as first-line disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA).
This open-label, randomized controlled, parallel-group, 3-month trial randomly assigned 100 RA patients to tofacitinib 10 mg daily (49 patients) or MTX 25 mg subcutaneously weekly (51 patients). The primary end point was low disease activity (LDA) measured with Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and the secondary end point was LDA and remission measured by DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Health Assessment Questionnaire Disability Index (HAQ-DI) response and mean reduction of core set of outcomes from baseline at 12 weeks were also analyzed as secondary end points. In addition, acute-phase reactants and composite measurements among groups were examined.
LDA in DAS28-CRP was achieved in 17 (34.7%) tofacitinib patients and 18 (35.3%) MTX patients (p = .95). Fourteen (28.6%) and 11 (21.6%) tofacitinib and MTX patients, respectively, achieved LDA by DAS28-ESR (p = .42). Tofacitinib and MTX groups achieved LDA similarly in CDAI (36.7% against 37.3%; p = .96) and SDAI (38.8% vs. 39.2%; p = .96). There was no significant difference in achieving remission between the groups. At 12 weeks, tofacitinib reduced ESR and CRP (p < .05). Composite measures and functional status decreased within groups but not between groups (p > .05). Five (13.51%) tofacitinib patients developed hypertension. MTX caused gastrointestinal problems in 12 (30%) individuals. Two MTX (5%) and two tofacitinib (5.4%) patients had increased liver enzymes and renal impairment, respectively. Tofacitinib had 5.4% infection compared with 5% for MTX.
As tofacitinib may be more effective than MTX according to previous reports such as the ORAL Start study, high-dose MTX (25 mg/week, subcutaneously) used in this study may be as efficacious as tofacitinib in patients with established RA who were DMARD naive or had not received a therapeutic dose of DMARDs. However, adverse effects differed between groups. Registered on: ClinicalTrials.gov; ID: NCT04464642.
比较托法替布和甲氨蝶呤（MTX）作为类风湿关节炎（RA）的一线疾病修饰抗风湿药物（DMARDs）。
这项开放标签、随机对照、平行组、3 个月试验将 100 例 RA 患者随机分为托法替布 10mg 每日组（49 例）或 MTX 25mg 每周皮下注射组（51 例）。主要终点是用 C 反应蛋白（DAS28-CRP）测量的低疾病活动度（LDA），次要终点是用 DAS28-红细胞沉降率（ESR）、临床疾病活动指数（CDAI）和简化疾病活动指数（SDAI）测量的 LDA 和缓解。健康评估问卷残疾指数（HAQ-DI）应答和 12 周时从基线开始的核心评估结果的平均降低也作为次要终点进行分析。此外，还检查了各组的急性期反应物和综合测量值。
托法替布组 17 例（34.7%）和 MTX 组 18 例（35.3%）患者达到 DAS28-CRP 的 LDA（p=0.95）。托法替布组 14 例（28.6%）和 MTX 组 11 例（21.6%）患者分别通过 DAS28-ESR 达到 LDA（p=0.42）。托法替布组和 MTX 组在 CDAI（36.7%对 37.3%；p=0.96）和 SDAI（38.8%对 39.2%；p=0.96）中达到 LDA 的比例相似。两组间缓解率无显著差异。在 12 周时，托法替布降低了 ESR 和 CRP（p<0.05）。各组的综合测量和功能状态均有所下降，但组间无差异（p>0.05）。5 例（13.51%）托法替布患者发生高血压。MTX 导致 12 例（30%）患者出现胃肠道问题。MTX 组有 2 例（5%）和托法替布组有 2 例（5.4%）患者出现肝酶升高和肾功能损害。托法替布的感染率为 5.4%，而 MTX 的感染率为 5%。
根据 ORAL Start 等先前的研究报告，托法替布可能比 MTX 更有效，而本研究中使用的高剂量 MTX（25mg/周，皮下注射）在 DMARD 初治或未接受 DMARD 治疗剂量的已确诊 RA 患者中可能与托法替布同样有效。然而，两组间的不良反应不同。于 2023 年 04 月 17 日在 ClinicalTrials.gov 注册，编号为 NCT04464642。
