来氟米特和甲氨蝶呤联合治疗幼年类风湿性关节炎21例报告

目的　探讨来氟米特和甲氨蝶呤联合治疗幼年类风湿性关节炎的疗效及其安全性。方法　 40例多关节型幼年类风湿性关节炎 (JRA) ,分为治疗组和对照组。治疗组 (来氟米特和甲氨蝶呤 ) 2 1例 ,对照组 (甲氨蝶呤 ) 1 9例 ,各自接受相应药物治疗 2 6周。参与疗效综合评估的指标有关节压痛数、关节压痛指数、关节肿胀数、关节肿胀指数、关节整体功能评分、家长及医生评分、血沉、C 反应蛋白、类风湿因子水平。以总改善百分率对疗效进行综合评估。参与安全性评估的指标有黏膜、皮肤损害、胃肠反应、神经系统反应、血象、肝、肾功能。结果　治疗组用药后 1 2、2 6周的总平均改善率分别为 39 6 %、71 9% ;对照组的总平均改善率分别为 2 7 5 %、49 5 % ,两组差异有显著性 (P <0 0 1 )。治疗组用药后 1 2、2 6周的缓解率分别为 4 76 %、38 1 0 % ;对照组分别为 0、0 ,两组差异有显著性 (P <0 0 1 )。治疗组不良反应的发生率为 9 5 % ,主要表现为轻度白细胞减少和转氨酶升高 ;对照组不良反应发生率为 5 3 % ,主要表现为头晕、皮疹 ,症状轻微 ,两组差异无显著性 (P >0 0 5)。结论　来氟米特和甲氨蝶呤联合治疗幼年类风湿性关节炎的临床疗效显著优于单独使用甲氨蝶呤。但来氟米特有白细胞减少、转氨酶升高的不良反

Treatment of patients with juvenile rheumatoid arthritis with combination of leflunomide and methotrexate

OBJECTIVE: To evaluate the efficacy and safety of the combined therapy with leflunomide and methotrexate in the patients with juvenile rheumatoid arthritis (JRA). METHODS: Forty patients with active polyarthritis JRA were divided into 2 groups. Group 1 (n = 21) received leflunomide tablet (1 mg/(kg x day) on days 1 - 3; then [(0.2 - 0.4) mg/kg per day] plus methotrexate (0.3 mg/kg i.v. every two weeks till clinical remission, then oral tablet 0.2 mg/kg weekly). Group 2 received the same doses of methotrexate in the same way. Permitted concomitant drugs included stable doses of NSAIDs and a low dose of prednisone during the course of treatments. The clinical assessments included the number of tender and swollen joints, tender articular index, swollen articular index, general articular function score, parents and physician's evaluation score, erythrocyte sedimentation rate, serum C-reactive protein and rheumatoid factor. Drug safety was assessed by observing the reaction of mucous membrane, skin, gastrointestinal tract, nervous system, hematologic changes, liver and renal function. Statistical comparison between two groups was performed by using analysis of variance, t test and chi(2) test. RESULTS: Efficacy and safety was assessed at 12th and 26th week. Average improvement rate of leflunomide plus methotrexate group at 12th week and 26th week was respectively 39.6% and 71.9%; while that of control group was 27.5% and 49.5%, i.e., there was significant difference between the two groups (P < 0.01). Average remission rate of leflunomide plus methotrexate group at 12th week and 26th week was respectively 4.76% and 38.10%; while that of control group (methotrexate only) was respectively 0, 0. The clinical improvement in the group treated with leflunomide plus methotrexate was significantly greater than control group (P < 0.01). There was no significant difference (9.5% v 5.3%) in occurrence rate of side effects between the two groups. Side effects included leucocytopenia and raised aminotransferase. They were mostly mild and tolerable. CONCLUSION: The effect of the leflunomide and methotrexate therapy in patients with active JRA was better than methotrexate alone. The combination therapy with leflunomide and methotrexate was safe and well tolerated.