99Tc-MDP治疗甲状腺相关眼病的临床研究

A clinical study on 99Tc-MDP for thyroid-associated ophthalmopathy

目的探讨锝-亚甲基二磷酸盐注射液(99Technetium-methylenediphosphonate injection,99Tc-MDP)治疗甲状腺相关眼病(TAO)的疗效和安全性。方法选择2016年10月至2018年10月于大连大学附属中山医院治疗的活动性中重度TAO患者50例,按随机数字表分为治疗组(25例)和对照组(25例),最终完成治疗及随访者分别为21、20例。治疗组每个疗程应用30套99Tc-MDP治疗10 d,疗程间隔20 d,共3个疗程;对照组静点甲强龙脉冲治疗,前6周每周500 mg,后6周每周250 mg,总量4.5 g。分别于治疗12周和24周随访时进行临床活动度评分(CAS)和突眼度评估(CAS减少值≥2分、突眼度减少值≥2 mm判定为有效改善)。以治疗12周时的不良反应发生率评估安全性。结果治疗12周时,治疗组和对照组CAS和突眼度改善情况比较差异无统计学意义[(2.48±0.60)、(2.20±0.62)分,(2.57±1.02)、(2.20±1.09)mm,P均>0.05];但治疗组不良反应发生率低于对照组[4.8%(1/21)比40.0%(8/20),P<0.05]。24周随访时,治疗组CAS改善情况优于对照组[(3.86±0.67)、(3.05±0.59)分,P<0.05];而两组在突眼度改善方面差异无统计学意义[(3.17±0.60)、(2.88±0.57)mm,P>0.05];两组总体有效率(综合CAS、突眼度评判)比较差异无统计学意义(P>0.05)。结论99Tc-MDP在改善TAO患者的总体疗效方面与甲强龙脉冲治疗效果相当,在持续性改变TAO患者CAS方面优于甲强龙;应用99Tc-MDP治疗TAO,不良反应发生率明显低于甲强龙。

Objective To investigate the efficacy and safety of 99Technetium-methylenediphosphonate injection(99Tc-MDP)in the treatment of thyroid associated ophthalmopathy(TAO).Methods The trail was conducted in Affiliated Zhongshan Hospital of Dalian University.Patients were recruited from October 2016 to October 2018.Fifty patients with active moderate to severe TAO were randomly assigned to receive 99Tc-MDP(n=25)or methylprednisolone administered intravenously(n=25),the final completion of treatment and follow-up were 21 and 20 cases,respectively.In 99Tc-MDP group,30 sets of 99Tc-MDP were applied to each course of treatment for 10 d,with a course interval of 20 d,a total of 3 courses of treatment.Patients in methylprednisolone group were given a pulse regimen,once every week for a total of 12 infusions,altogether 4.5 g in 12 weeks.The clinical activity score(CAS)and exophthalmos were assessed in a patient at weeks 12 and 24,respectively.A response was defined as a reduction of 2 points or more in CAS and reduction of 2 mm or more in exophthalmos.Safety was assessed according to the incidence of adverse events at week 12.Results At week 12 treatment,no significant difference was observed in CAS and exophthalmos between the two groups[CAS:(2.48±0.60),(2.20±0.62)points,exophthalmos:(2.57±1.02),(2.20±1.09)mm,P>0.05].Adverse events in 99Tc-MDP group was significantly lower than that in methylprednisolone group[4.8%(1/21)vs 40.0%(8/20),P<0.05].At week 24,the reduction in the CAS in 99Tc-MDP group was significantly greater than that in methylprednisolone group[CAS:(3.86±0.67),(3.05±0.59)points,P<0.05].The difference in exophthalmos of patients between the two groups was not statistically significant[(3.17±0.60),(2.88±0.57)mm,P>0.05].The difference in total effective rate of patients between the two groups was not statistically significant(P>0.05).Conclusion 99Tc-MDP regimen could provide similar benefit to methylprednisolone pulse therapy for those patients with TAO,but with longer reduction in CAS and less adverse events.