白芍总苷与甲氨蝶呤和柳氮磺胺吡啶联合应用治疗强直性脊柱炎的疗效及优越性观察

背景白芍总苷为白芍中提取的有效成分,具有较好的抗炎和镇痛作用. 目的观察白芍总苷联合甲氨蝶呤和柳氮磺胺吡啶治疗强直性脊柱炎的协同疗效作用及其毒副作用. 设计随机对照观察. 单位广州省中医院风湿科. 对象选择2003-06/2004-04广东省中医院风湿科门诊收治强直性脊柱炎患者80例.随机分为2组,每组各40例.签书面知情同意书. 方法治疗组口服白芍总苷胶囊2粒,3次/d;甲氨蝶呤10 mg/次,1次/周;柳氮磺胺吡啶0.5g/次,3次/d.对照组口服甲氨蝶呤和柳氮磺胺吡啶,剂量和方法同治疗组.两组均用尼美舒利,0.1g/次,2次/d.疗程均为3个月.于治疗前及治疗4,8,12周进行脊柱功能评价和实验室检查. 主要观察指标主要结局Bath强直性脊柱炎活动指数、Bath强直性脊柱炎功能指数,晨僵时间,全身和脊柱疼痛Likert 4级积分以及患者和医生的总体评价积分.次要结局①血沉、C反应蛋白、Schober实验、扩胸度、枕墙距和指地距.②不良事件和副反应. 结果治疗组完成了38例和对照组完成了37例患者的观察.①两组患者主要疗效指标中Bath强直性脊柱炎活动指数和功能指数、晨僵时间、全身疼痛积分、脊柱疼痛积分、患者的总体评价积分、医生的总体评价积分结果两组治疗4,8和12周与各自0周比较均明显下降(P＜0.05);治疗组4周时Bath强直性脊柱炎活动指数、全身和脊柱疼痛Likert4级积分、患者和医生的总体评价积分及8周和12周各指标均较对照组有显著下降(P＜0.05).②两组患者次要疗效指标中血沉、C反应蛋白、Schober试验、扩胸度、枕墙距、指地距的评估结果治疗组4,8和12周各指标较治疗前显著下降(P＜0.05);对照组4周时Schober试验、扩胸度、指地距及8和12周较治疗前显著下降(P＜0.05).治疗组12周时血沉、C反应蛋白、扩胸度、指地距较对照组显著下降.③不良事件和副反应两组治疗中均有出现短暂转氨酶升高和白细胞下降,未处理或保肝后恢复正常,无一例停药.治疗组不良反应发生率较对照组低10%(3/30),57%(17/30),P＜0.05]. 结论白芍总苷联合甲氨蝶呤和柳氮磺胺吡啶治疗强直性脊柱炎具有增效作用,且未出现特殊不良反应,安全性高.

Effect and superiority of the application of total glucosides of white peony,combined with methotrexate and sulfasalazine in the treatment of ankylosing spondylitis

BACKGROUND: Total glucosides of paeony, effective component extracted from peony, has good inflammatory and analgesic effect. OBJECTIVE: To investigate the curative effect and side effect of total glucosides of paeony combined with methotrexate and sulfasalazine in the treatment of ankylosing spondylitis. DESIGN: Randomized and controlled observation SETTING: Department of Rheumatology , Guangdong Hospital of Traditional Chinese Medicine PARTICIPANTS: Totally 80 inpatients with ankylosing spondylitis hospitalized in the Clinic of Department of Rheumatology, Guangdong Hospital of Traditional Chinese Medicine from June 2003 to April 2004 were involved. The patients were randomly divided into 2 groups with 40 patients in each group. Informed consent was obtained. METHODS: Experimental group: 2 capsules of total glucosides of peony was taken orally, three times per day; methotrexate 10 mg/time, once per week; sulfasalazine 0.5 g/time, three times per day. Control group:methotrexate and sulfasalazine were taken orally and the dosage and method were the same as those in the experimental group. Two groups all used the same NSAID (Nimesulide) , 0.1 g/time, twice per day. The period of the treatment was 3 months. Evaluation of spinal column function and laboratory examination was performed before treatment and 4, 8 and 12 weeks after treatment. MAIN OUTCOME MEASURES: Primary outcomes: Bath ankylosing spondylitis activity index, Bath ankylosing spondylitis function index 1-2],duration of morning stiffness, systemic pain and spinal pain on a four point Likert scale, overall assessment of patient and physician on a four point scale. Secondary outcomes: ①erythrocyte sedimentation, C-reaction protein,Schober test, chest expansion, Occiput to wall distance and finger to floor distance.② Adverse events and side effects. RESULTS: The observation of 38 patients in the experiemtnal group and 37 patients in the control group was completed. ①Result of Bath ankylosing spondylitis activity index, Bath ankylosing spondylitis function index,duration of morning stiffness, pain and spinal pain on a four point Likert scale, overall assessment of patient and physician on a four point scale:The indices at week 4, 8 and 12 werevmore significantly decreased than those before treatment in each group (P ＜ 0.05); the Bath ankylosing spondylitis activity index, pain and spinal pain on a four point Likert scale,overall assessment of patient and physician on a four point scale at week 4and all the indices at week 8 and 12 were more significantly decreased than those in the control group (P ＜ 0.05). ② Evaluation result of Erythrocyte sedimentation rate (ESR) and C reaction protein, Schober test, chest expansion , occiput to wall distance and finger to floor distance: Each index at week 4, 8 and 12 in the experimental group were significantly decreased than those before treatment (P ＜ 0.05), those at week 8 and 12 in the control group were more significantly decreased than those before treatment (P ＜ 0.05). ESR , C reactive protein (CRP) , chest expansion and finger to floor distance at week 12 in the control group were more significantly decreased . ③ Adverse events and side effects: All adverse reactions occurred transiently during the course of disease in the two groups. Undisposed or after having taken live-protective medicine, all patients recovered.Drug was not withdrawn in any case.The incidence of adverse reaction in the experimental group was lower than that in the control group 10％ (3/30),57％(17/30) ,P ＜ 0.05]. CONCLUSION: Combination of total glucosides of paeony, methotrexate and sulfasalazine has an enhanced effect and better safety without special adverse reaction in the treatment of ankylosing spondylitis.