霉酚酸酯治疗甲状腺相关性眼病临床对照研究

Therapeutic outcomes of mycophenolate mofetil and three other immunosuppressants in patients with Graves’ ophthalmopathy

目的 :对比霉酚酸酯等几种不同免疫抑制药对甲状腺相关性眼病 (TAO)或称Graves眼病 (Graves′ ,Ophthal mopathy ,GO)的疗效 ,旨在寻求免疫治疗的有效手段。 方法 :将TAO 5 4例 ,分成A、B两大组 ,A组随机采用泼尼松 (1 6例 ,完成治疗者 1 3例 )或雷公藤总甙 (TⅡ ,1 5例 )治疗 ;B组随机采用霉酚酸酯 (MMF ,1 2例 )或环孢素 (CsA ,1 1例 )治疗 ,疗程 1 2周。疗效判断采用改良Given Wilson积分指数系统 ,设定积分下降或上升≥ 3分为好转或恶化 ,<3分为无变化。 结果 :1 2周末 ,泼尼松组 1 3例中 7例 (5 4 % )好转 ,6例 (4 6 % )无变化 ;TⅡ 组 1 0例 (6 7% )好转 ,5例 (33% )无变化 ;MMF组 1 1例 (92 % )好转 ,1例 (8% )无变化 ;CsA组 5例 (4 5 % )好转 ,6例 (5 5 % )无变化。MMF好转率高于CsA(P <0 .0 5 ) ;TⅡ 组与泼尼松组比较 ,无显著差异 (P >0 .0 5 )。各组治疗后眼病分值均有一定程度下降 (P <0 .0 1 ) ,下降幅度从大到小依次为MMF、TⅡ 、泼尼松和CsA。泼尼松组 3例 (1 9% )体重增加 >5 % ,2例血糖增高 ,停药后血糖恢复 ,该组共 3例退出治疗 ,其他各组无因药物不良反应而中途退出者。MMF组未发现有明确的药物不良反应。 结论 :新型免疫抑制药MMF用于治疗Graves眼病疗效优于CsA 。

Objective:In this study, we analyzed the efficacy and tolerability of mycophenolate mofetil and three other immunosuppressants in Graves’ ophthalmopathy (GO) patients. Methods:Fifty four untreated GO patients were enrolled in this study. The diagnosis of GO was based on the presence of the typical clinical features and excluding of the possibility of cranial/orbital diseases, and the severity of ophthalmopathy was at least equal to or more severe than Class 2 in NO SPECS classification. Those who could afford were randomly assigned to receive either mycophenolate mofetil (MMF, n =12, 16～18 mg per kilogram per day) or cyclosporin A (CsA, n =11, 5～6 mg per kilogram of body weight per day) therapy. The others were randomly assigned to be given either prednisone ( n =16, finished in 13 case, 40 mg per day for 4 weeks, 20 mg for 4 weeks, and 10 mg for 4 weeks) or tripterygium multi glycosides (T Ⅱ , n =15, 30～60 mg per day). The disease severity and therapeutic response were quantitatively assessed according to the Ophthalmopathy Index Scoring System from Given wilson (1989) with sensibly modified. The improvement or progression of ophthalmopathy was defined if the variation, either increase or decrease of the score, reached 3 or more in the ophthalmopathy index. If this did not occur, a lack of response was indicated. In patients who had hyperthyroidism, antithyroid drugs were also administered.Results:After 12 week therapy, 7 (54 percent) of the 13 treated with prednisone improved, the remaining 6 (46 percent) lacked response. In T Ⅱ group, 10 (67 percent) of 15 responded to the therapy, 5 (33 percent) had no change. There was no significant difference in clinical response between the above 2 groups ( P >0.05). Five CsA treated and 11 MMF treated patients responded to therapy (45 percent vs 92 percent; P < 0.05) . It seems that MMF is more effective than CsA in the treatment of GO although a significant decrease ( P <0.01) in the mean score of the CsA group has also been shown at the end of the course. None of all the 51 patients in the 4 groups had worsening of ophthalmopathy. Among 16 patients in prednisone group, 3 (19 percent) gained body weight by more than 5 percent, 2 (13 percent) developed impaired glucose tolerance (IGT). These two patients and one of the three weight gaining patients ceased the therapy. Impermanent menopause happened in 1 (11 percent) of the females in T Ⅱ group at the sixth month in sequel treatment after the course. Conclusion:MMF may be more effective than CsA in the treatment of Graves’ophthalmopathy. T Ⅱ may have a equal effectiveness and perhaps a better tolerability than prednisone in the immunotherapy of Graves’ ophthalmopathy.