大剂量泼尼松与环磷酰胺-长春新碱-泼尼松方案治疗甲状腺相关眼病的临床疗效比较

Treatment of thyroid-associated ophthalmopathy:comparative study between prednisone and COP therapy

目的探讨大剂量泼尼松方案与环磷酰胺长春新碱泼尼松(COP)方案治疗甲状腺相关眼病(TAO)的临床疗效。方法选择2000年8月至2003年7月在北京协和医院眼科确诊的27例甲状腺相关眼病患者,参考患者病情严重程度及对化疗药物的依从性将其分为两组,泼尼松组13例,COP组14例,两组患者的性别构成、年龄比较差异均无统计学意义(P>0.05)。分别比较两组患者组内和组间治疗前后临床活动度积分(CAS)、病情严重程度、眼外肌厚度及24h尿中糖胺聚糖(GAG),分析临床疗效。结果COP组治疗前后CAS积分分别为6.5±1.6和1.9±1.3;泼尼松组为4.4±1.8和1.6±1.1,治疗前CAS积分COP组显著高于泼尼松组(P<0.001),两组治疗前后组内分别比较差异均有统计学意义(P<0.01)。COP组治疗前后眼外肌的厚度分别为(6.8±1.7)mm和(5.3±1.1)mm;泼尼松组为(6.5±1.5)mm和(5.8±1.1)mm;两组治疗前后组内分别比较差异均有统计学意义(P<0.01)。COP组与泼尼松组治疗后眼外肌厚度分别减少(22.4±4.4)%和(13.3±4.6)%,组间比较差异有统计学意义(P<0.01)。两组治疗后病情显著缓解。治疗前后的24h尿GAG水平:COP组(7例)分别为(40.6±10.1)mg/24h和(15.7±5.1)mg/24h,泼尼松组(5例)分别为(33.6±6.6)mg/24h和(16.7±2.5)mg/24h,均降至正常;组内分别比较差异均有统计学意义(P<0.01)。结论大剂量泼尼松方案和COP方案均是治疗TAO的有效方案,统计学分析结果显示COP方案较泼尼松方案更有效,提示COP方案可能适合治疗活动度高、病情严重的TAO患者。

Objective To evaluate the efficacy of two therapies, high-dose prednisone and COP in the treatment of patients with active thyroid-associated ophthalmopathy （ TAO ）. Methods According to severity and compliance, the patients admitted in Peking Union Medical College Hospital from August 2000 to July 2003 were divided into two groups. Thirteen patients with active TAO were treated with high-dose prednisone. The initial dosage was 1.5-2.0 mg · kg^-1 · d^-1 （ maximal dosage 200 mg）, tapering gradually, and shifting to alternate-day treatment. Fourteen patients in the COP group were treated with eyelophosphamide （CTX）,oneovin （VCR） and prednisone. This therapy was modified from CHOP in the treatment of patients with non-Hodgkin＇s lymphoma： CTX 600 mg/m^2 ,VCR 1.1 mg/m^2 were administrated by intravenous infusion every 2-4 weeks, prednisone was given orally at 1 mg · kg^-1 · d^-1 for seven days after each infusion. The duration of treatment for both groups was approximately 10 months. The parameters including clinical activity score （CAS） ,thickness of extra-ocular muscle as well as 24 h urinary GAG were used to evaluate the efficacy of treatment in both groups. Results There was no significant difference in age and sex between two groups. However the patients in the COP group were more severe than that in prednisone group （ P 〈 0. 05 ）. CAS in the patients treated with prednisone before and after treatment were 4. 4 ± 1.8,1.6 ± 1.1 respectively, that in patients treated with COP were 6. 5 ± 1.6,1.9 ± 1.3 respectively.All these changes were highly significant （P 〈 0.01 ）. The thickness of extra-ocular muscles in the patients treated with prednisone decreased from （ 6. 5 ± 1.5 ） mm to （ 5.8 ± 1.1 ） mm, that in patients treated with COP decreased from （ 6. 8 ± 1.7 ） mm to （ 5.3 ± 1.1 ） mm. Both changes were highly significant （ P 〈 0. 01 ）. Comparative study of the changes in the thickness of extra-ocular muscle by percentage between two groups demonstrated that the muscle thickness in patients treated with COP was decreased by （23. 7 ± 4. 3 ） % , that in patients treated with prednisone was by （ 13. 3 ±4. 6） %. The difference between the two groups was highly significant （ P 〈 0. 01 ）. The 24 h urinary GAG level in patients treated by prednisone decreased from （33.6 ±6.6） mg,/24 h before treatment to （16.7 ±2.5 ） mg,/24 h after treatment. Those in COP group were （40. 6 ± 10. 1 ） mg/24 h and （ 15. 7±5. 1） mg/24 h respectively. The difference was significant （P 〈 0.01 ） in each group. There were no serious complications during treatment. Conclusions Both the prednisone and COP therapy are effective in the treatment of patients with active TAO. The preliminary results indicate that COP is more effective than prednisone, it suggests that COP might be feasible for treating patients with progressive and severe TAO. （Chin J Ophthalmol, 2005,41：781-785 ）