From the Departments of Rheumatology.
Gynecology.
J Clin Rheumatol. 2019 Aug;25(5):197-202. doi: 10.1097/RHU.0000000000000810.
To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential.
We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us.
Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]).
Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.
综述叶酸（叶酸或亚叶酸）补充治疗甲氨蝶呤（MTX）治疗类风湿关节炎（RA）的益处和危害的证据，评估叶酸补充是否会降低 MTX 毒性或降低 MTX 疗效，以及是否需要更高的 MTX 剂量。
我们进行了一项敏感的检索策略，系统地检索了 Medline、Embase、Web of Science 和 Cochrane 图书馆数据库，检索时间截至 2016 年 6 月 2 日。还检索了主要风湿病会议和主要试验登记处的摘要，以检索所有我们感兴趣的随机对照试验。
纳入了 7 项研究，共 709 例患者。这些试验之间没有显著的异质性。对于接受 MTX 治疗的 RA 患者，给予叶酸的患者发生肝转氨酶升高（比值比 [OR] 0.15；95%置信区间 [95%CI] 0.10，0.23 [p < 0.00001]）和恶心、呕吐等胃肠道副作用（OR 0.71；95%CI 0.51，0.99 [p = 0.04]）的可能性较小。叶酸似乎通过降低与安慰剂相比的患者停药率来促进 MTX 的依从性（OR 0.29；95%CI 0.21，0.42 [p < 0.00001]）。叶酸和安慰剂之间的口腔溃疡发生率无统计学差异（OR 0.83；95%CI 0.57，1.22 [p = 0.35]）。由于这些试验中的疾病活动标志物不一致，因此无法确定叶酸补充是否降低了 MTX 的疗效。此外，我们比较了高剂量叶酸（每周≥25mg）和低剂量叶酸（每周≤10mg）对 MTX 疗效的影响，发现无统计学差异（OR 2.07；95%CI 0.81，5.30 [p = 0.13]），也无统计学差异对 MTX 毒性（OR 1.56；95%CI 0.80，3.04 [p = 0.19]）。
叶酸补充可降低 RA 患者 MTX 治疗的肝毒性和胃肠道副作用发生率。它还可以降低患者停止 MTX 治疗的可能性。尽管它似乎降低了口腔溃疡的发生率，但无统计学意义。高剂量叶酸和低剂量叶酸对 MTX 疗效或毒性无显著差异。
