From the Department of Medicine, University of Otago, Christchurch.
Departments of Rheumatology, Immunology, and Allergy.
J Clin Rheumatol. 2019 Oct;25(7):284-287. doi: 10.1097/RHU.0000000000000848.
BACKGROUND/OBJECTIVE: The aim of this study was to determine whether reducing the dose of supplemental folic acid used in conjunction with methotrexate (MTX) therapy in people with active rheumatoid arthritis (RA) improved disease control and/or increased MTX-related adverse effects.
A randomized double-blind randomized controlled trial comparing 5 mg/wk and 0.8 mg/wk folic acid was undertaken. Rheumatoid arthritis patients on MTX for 3 months or more at a stable dose for 1 month or more were recruited. All participants had DAS28 of 3.2 or greater or required a change in therapy determined by the treating clinician. Disease activity, full blood count, liver function tests, red blood cell (RBC) folate, and RBC MTX polyglutamates were assessed at weeks 0, 4, 8, 16, and 24 along with reports of adverse events.
Forty participants were recruited. The mean (SD) change in RBC folate between week 0 and 24 was +87.9 (57.4) nmol/L in the high-dose group and -113.3 (65.7) nmol/L in the low-dose group (p < 0.05). There was no significant difference in the change in DAS28 between the high- and low-dose groups at 24 weeks (-0.13 [95% confidence interval, -0.69 to 0.43] vs -0.25 [-0.87 to 0.37], respectively [p = 0.78]). There was no significant difference in MTX-related adverse effects between the 2 groups.
A reduction in RBC folate secondary to reduction in folic acid dose was not associated with a change in RA disease activity or MTX-related adverse effects. The prevention of MTX-related adverse effects remains the primary reason for coprescribing folic acid with MTX.
Australian New Zealand Clinical Trials Registry (ANZCTR12610000739011).
背景/目的：本研究旨在确定在患有活动期类风湿关节炎（RA）的人群中，减少与甲氨蝶呤（MTX）联合使用的补充叶酸剂量是否可以改善疾病控制和/或增加 MTX 相关不良反应。
进行了一项随机双盲对照临床试验，比较了 5 毫克/周和 0.8 毫克/周的叶酸剂量。招募了正在接受 MTX 治疗 3 个月或以上且稳定剂量治疗 1 个月或以上的 RA 患者。所有参与者的 DAS28 均大于 3.2，或需要根据治疗医生的判断进行治疗改变。在 0、4、8、16 和 24 周时评估疾病活动度、全血细胞计数、肝功能检查、红细胞（RBC）叶酸和 RBC MTX 多谷氨酸，并报告不良反应。
共招募了 40 名参与者。高剂量组在第 0 周至 24 周期间 RBC 叶酸的平均（SD）变化为+87.9（57.4）nmol/L，低剂量组为-113.3（65.7）nmol/L（p<0.05）。在 24 周时，高剂量组和低剂量组之间 DAS28 的变化无显著差异（分别为-0.13[95%置信区间，-0.69 至 0.43]和-0.25[-0.87 至 0.37]，p=0.78）。两组之间 MTX 相关不良反应无显著差异。
叶酸剂量减少导致 RBC 叶酸减少与 RA 疾病活动度或 MTX 相关不良反应无变化相关。与 MTX 联合使用叶酸的主要原因仍然是预防 MTX 相关不良反应。
澳大利亚新西兰临床试验注册中心（ANZCTR12610000739011）。
