不同浓度A型肉毒毒素治疗偏侧面肌痉挛疗效观察:一项多中心随机双盲交叉设计临床试验

Therapeutic effects of botulinum toxin A at different dilutions in hemifacial spasm patients: a multicenter,randomized,double-blind and self-crossover controlled trial

研究背景目前有关A型肉毒毒素治疗偏侧面肌痉挛注射浓度的各项研究报道不尽相同,其疗效及药物不良反应发生率亦差异较大,且很少有随机对照临床试验。本研究拟评价两种不同浓度A型肉毒毒素治疗偏侧面肌痉挛的疗效及安全性。方法选择4所医疗单位共80例偏侧面肌痉挛患者,随机以高浓度(50 U/ml)和低浓度(25 U/ml)局部注射A型肉毒毒素,复发后采取高、低浓度交叉再注射,分析两组疗效和药物不良反应发生率。结果两种Α型肉毒毒素浓度治疗偏侧面肌痉挛均有效(P=0.000)。不同治疗顺序疗效及药物起效时间比较差异无统计学意义(均P>0.05),但高浓度组疗效持续时间更长(P=0.000);治疗后8天至3个月两组Cohen分级下降值差异无统计学意义(P=0.863),治疗4、5个月时两组Cohen分级下降值差异有统计学意义(均P=0.000);治疗时间超过6个月时,两组Cohen分级下降值相近(P=0.515)。治疗期间高浓度组药物不良反应发生率高于低浓度组(P=0.000),且持续时间更长(P=0.000);但两组总体不良反应程度轻微,不经特殊处理均可自愈,无一例出现药物过敏或全身性中毒反应。结论 A型肉毒毒素局部注射治疗偏侧面肌痉挛安全有效,高浓度重复注射间隔时间更长,患者针刺疼痛感降低,经济负担减轻,但药物不良反应相对明显且持续时间更长。

Background At present, the concentration of botulinum toxin A （BTX-A） injection in the treatment of hemifacial spasm （HFS） is different in various reports, and the efficacy and adverse drug reactions incidence are varied. Few randomized controlled trials are related to this subject. The aim of this study is to evaluate the efficacy and safety of two concentrations of BTX-A in the treatment for HFS. Methods Eighty patients with HFS from 4 research centers were included in this multicenter randomized double-blind self-crossover controlled trial. Patients were randomly assigned to high-density group （given injection of 50 U/ml BTX-A） and low-density group （given injection of 25 U/ml BTX-A）. They weresubjected to a cross- over repetitive injection of BTX- A of different concentrations after recurrence. Therapeutic efficacy and adverse effect were compared between two groups. Results Both high-density and low-density BTX-A were effective. Cohen spasms strength grade scores before and after the treatment in high-density group were 2.89 ± 0.53 vs 0.24 ± 0.46, while in low-density group was 2.89± 0.55 vs 0.24 ±0.46 （P = 0.000, for all）. The therapeutic efficacy was not different between the two groups in different concentration order （P 〉 0.05）. But the lasting time of therapeutic efficacy was much longer in high-density group than that of low-density group （4.18± 0.49 months vs 3.26 ± 0.44 months, P = 0.000）. Within three months, there was no significant difference between the two groups in the decrease of Cohen spasms strength grade scores （2.65 ± 0.62 vs 2.66 ± 0.66, P = 0.863）. Four months after treatment, it was different between the two groups in the decrease of Cohen spasms strength grade scores （2.60 ± 0.65 vs 1.70 ±0.72, P = 0.000）. Five months after treatment, it was also different between the two groups in the decrease of Cohen spasms strength grade scores （1.56 ± 0.94 vs 0.25 ±0.49, P = 0.000）. After six months of treatment, there was no significant difference between the two groups in the decrease of Cohen spasms strength grade scores （0.08 ± 0.27 vs 0.05 ± 0.22, P = 0.515）. There were no allergic reactions and systemic adverse effects. The adverse effect of the high-density group was more than that of the low-density group （26.56% vs 7.81%, P = 0.000）. All of the adverse effects were mild and temporary, and no special intervention was involved. The duration of adverse effect was longer in high-density group [（5.71 ± 1.61） weeks vs （3.16 ± 0.62） weeks, P = 0.000]. Conclusion This study showed that injection of BTX-A with different concentrations in HFS patients was safe and effective. With high-density, the repeated injection interval time was longer; the pain of patients was reduced; the cost of treatment was low; but adverse drug reactions were relatively evident and lasted for a longer period of time.