夏枯草制剂治疗桥本甲状腺炎系统评价与试验序贯分析

Systematic review and trail sequential analysis of preparation of Xiakucao for Hashimoto′s thyroiditis

为系统评价口服夏枯草制剂联合左旋甲状腺素(levothyroxine,LT4)治疗桥本甲状腺炎(hashimoto thyroiditis,HT)的疗效及安全性,以期为未来临床应用提供循证依据。该研究全面系统检索四大中文数据库和三大英文数据库,检索时间从建库至2019年12月。采用Cochrane系统偏倚风险评估工具和GRADE证据分级标准,对纳入研究进行质量评估,并用RevMan 5.3软件对结局指标进行Meta分析。使用TSA 0.9(trail sequential analysis)软件估算Meta分析的所需样本量。最终纳入11项随机对照试验,共1215例患者。试验组均为口服夏枯草制剂联合西医常规LT4治疗,对照组均为西医常规LT4治疗。Meta分析结果表明,口服夏枯草制剂联合LT4在甲状腺功能及自身抗体的改善、缩小甲状腺腺体及结节、改善神疲乏力、畏寒肢冷等症状方面临床治疗总有效率高于对照组(RR=1.15,95%CI[1.09,1.21]),并且能够显著降低血清抗甲状腺过氧化物酶抗体TPO-Ab滴度(SMD=-0.91,95%CI[-1.40,-0.41]),缩小甲状腺左叶(MD=-1.46,95%CI[-1.82,-1.11])、右叶(MD=-1.45,95%CI[-1.96,-0.94])、峡部厚度(MD=-1.08,95%CI[-1.20,-0.95]),差异有统计学意义。使用GRADE系统评价结局指标,结果显示证据体质量等级为低或极低。TSA分析表明,目前累计研究样本量已经达到期望值,但结果可能受到1项高偏倚风险研究的影响,证据的效应强度不高。夏枯草制剂联合LT4对比单用LT4治疗HT在疗效、提高血清TPO-Ab抗体滴度、改善甲状腺激素水平、缩小甲状腺腺体有一定优势。然而受纳入研究质量影响,该研究结论的证据强度不足,尚需更多高质量、报告详细的随机对照试验进一步证实。

To systemically evaluate the clinical efficacy and safety of oral preparation of Xiakucao with levothyroxine(LT4)on Hashimoto′s thyroiditis(HT),so as to provide the evidence for its clinical application in the future.All the included studies were retrieved from four Chinese databases and three English databases from their inception to December 2019.ROB assessment tool of cochrane system and the evidence classification recommended by GRADE were used to evaluate the quality of evidences in all included studies.RevMan 5.3 was used for Meta-analysis of the outcomes.Software TSA 0.9(trail sequential analysis)was used to estimate the sample size for Meta-analysis.The results showed that 11 randomized controlled trials and totaling 1215 patients were included.Preparation of Xiakucao combined with LT4 was adopted as intervention in experimental group,while patients in control group were treated with LT4 alone.Meta-analysis results showed that as compared with control group,the rate of total efficacy in experimental group was significant improved,including improvement of thyroid function and thyroid autoantibodies,shrinkage of thyroid gland and nodule,and improvement of clinical symptoms such as fatigue and cold intolerance(RR=1.15,95%CI[1.09,1.21]).The experimental group significantly decreased the serum level of thyroperoxidase antibody TPO-Ab(SMD=-0.91,95%CI[-1.40,-0.41]),and reduced the size of left thyroid lobe(MD=-1.46,95%CI[-1.82,-1.11]),right thyroid lobe(MD=-1.45,95%CI[-1.96,-0.94])and isthmus of thyroid gland(MD=-1.08,95%CI[-1.20,-0.95]).After evaluation based on GRADEpro,the results showed that the evidence quality of all included studies was low or very low.The result of TSA showed that the cumulative sample size had reached the expected value.However,the pooled results may be affected by one study with high bias risk,with not so high effect intensity of evidences.From this review,we can see that in treatment of HT,intervention of preparation of Xiakucao combined with LT4 has advantages on improvement of clinical efficiency,decreasing serum level of TPO-Ab and shrinkage of thyroid gland.However,due to the quality of evidence,more rigorously designed and high-quality trials are needed in the future to verify the clinical efficacy and safety of preparation of Xiakucao in treating HT.