Abstract：
BACKGROUND: Supplemental methotrexate (MTX) may affect the clinical course of Graves\' disease (GD).
OBJECTIVE: Evaluate efficacy of add-on MTX on medical treatment in GD.
METHODS: Prospective, open-label, randomized supplementation controlled trial.
METHODS: Academic endocrine outpatient clinic.
METHODS: One hundred and fifty-three untreated hyperthyroid patients with GD.
METHODS: Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12-18 in euthyroid patients.
METHODS: Discontinuation rate at months 18 in each group.
RESULTS: In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15-18 (50.0 vs. 33.3%, P=0.043, 95% CI 1.020 to 3.922; and 55.6 vs 38.9%, P=0.045, 95%CI 1.011 to 3.815, respectively). The decrease in TRAb levels in the MTX with MMI group was significant from baseline to months 6 compared to the MMI alone group [MTX+MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P= 0.039) and became more significant from months 9 [MTX+MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P= 0.035] to months 18 (P < 0.01 in 15-18 months). A statistically significant difference between the levels of TRAb in the MTX with MMI group and the MMI group at 9-18 months. There were no significant differences in the levels of FT3, FT4 and TSH between two groups. No serious drug-related adverse events were observed in both groups(P=0.771).
CONCLUSIONS: Supplemental MTX with MMI resulted in higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12-18.
OBJECTIVE: Evaluate efficacy of add-on MTX on medical treatment in GD.
METHODS: Prospective, open-label, randomized supplementation controlled trial.
METHODS: Academic endocrine outpatient clinic.
METHODS: One hundred and fifty-three untreated hyperthyroid patients with GD.
METHODS: Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12-18 in euthyroid patients.
METHODS: Discontinuation rate at months 18 in each group.
RESULTS: In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15-18 (50.0 vs. 33.3%, P=0.043, 95% CI 1.020 to 3.922; and 55.6 vs 38.9%, P=0.045, 95%CI 1.011 to 3.815, respectively). The decrease in TRAb levels in the MTX with MMI group was significant from baseline to months 6 compared to the MMI alone group [MTX+MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P= 0.039) and became more significant from months 9 [MTX+MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P= 0.035] to months 18 (P < 0.01 in 15-18 months). A statistically significant difference between the levels of TRAb in the MTX with MMI group and the MMI group at 9-18 months. There were no significant differences in the levels of FT3, FT4 and TSH between two groups. No serious drug-related adverse events were observed in both groups(P=0.771).
CONCLUSIONS: Supplemental MTX with MMI resulted in higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12-18.
摘要：
背景：补充甲氨蝶呤（MTX）可能会影响Graves病（GD）的临床病程。
目的：评价加用MTX治疗GD的疗效。
方法：前瞻性，开放标签，随机补充对照试验。
方法：学术内分泌门诊。
方法：一百五十三名未经治疗的甲状腺功能亢进合并GD的患者。
方法：患者接受10mg/d的MTX与甲硫咪唑（MMI）或MMI。甲状腺功能正常的患者在12-18个月时停用MTX和MMI。
方法：每组18个月的停药率。
结果：在带有MMI的MTX组中，在15-18个月时，停药率高于MMI组（50.0vs.33.3%,P=0.043，95%CI1.020至3.922；55.6vs38.9%，P=0.045，95CI分别为1.011至3.815）。与单独使用MMI组相比，MTX与MMI组的TRAb水平从基线到6个月的下降显着[MTXMMI67.22％（43.12-80.32），MMI54.85%（33.18-73.76），P=0.039)，从第9个月开始变得更加显著[MTX+MMI77.79%(62.27-88.18)，MMI69.55%（50.50-83.22），P=0.035]至18个月(15-18个月P<0.01)。在9-18个月时，MTX与MMI组和MMI组中的TRAb水平之间存在统计学上的显着差异。两组FT3、FT4、TSH水平差异无统计学意义。两组均未发生严重的药物相关不良事件(P=0.771)。
结论：在12-18个月时，MMI补充MTX导致更高的停药率和TRAb水平下降至稳态水平的改善速度快于单独甲伊咪唑治疗。
目的：评价加用MTX治疗GD的疗效。
方法：前瞻性，开放标签，随机补充对照试验。
方法：学术内分泌门诊。
方法：一百五十三名未经治疗的甲状腺功能亢进合并GD的患者。
方法：患者接受10mg/d的MTX与甲硫咪唑（MMI）或MMI。甲状腺功能正常的患者在12-18个月时停用MTX和MMI。
方法：每组18个月的停药率。
结果：在带有MMI的MTX组中，在15-18个月时，停药率高于MMI组（50.0vs.33.3%,P=0.043，95%CI1.020至3.922；55.6vs38.9%，P=0.045，95CI分别为1.011至3.815）。与单独使用MMI组相比，MTX与MMI组的TRAb水平从基线到6个月的下降显着[MTXMMI67.22％（43.12-80.32），MMI54.85%（33.18-73.76），P=0.039)，从第9个月开始变得更加显著[MTX+MMI77.79%(62.27-88.18)，MMI69.55%（50.50-83.22），P=0.035]至18个月(15-18个月P<0.01)。在9-18个月时，MTX与MMI组和MMI组中的TRAb水平之间存在统计学上的显着差异。两组FT3、FT4、TSH水平差异无统计学意义。两组均未发生严重的药物相关不良事件(P=0.771)。
结论：在12-18个月时，MMI补充MTX导致更高的停药率和TRAb水平下降至稳态水平的改善速度快于单独甲伊咪唑治疗。
