目的 系统评价羟氯喹(HCQ)用于产科抗磷脂综合征(OAPS)的疗效及安全性。方法 计算机检索 PubMed、Embase、Cochrane Library 和 Web of Science、SinoMed、WanFang Data、CNKI和VIP数据库，搜集关于HCQ治疗OAPS的临床研究，检索时限均为从建库至2023年1月31日。由2名研究员筛选文献、提取资料并评价纳入研究的偏倚风险后，采用RevMan 5。4和GRADE profiler 3。6软件进行Meta分析及GRADE评价。结果 最终纳入5项队列研究，3项RCT，共644例OAPS患者(732例次妊娠)。Meta分析结果显示，与常规治疗相比，加用HCQ能显著提高OAPS患者的活产率[RR=1。29，95％CI(1。10，1。51)，P=0。001]及狼疮抗凝物转阴率[RR=1。29，95％CI(1。13，1。47)，P＜0。001]、抗心磷脂抗体转阴率[RR=1。27，95％CI(1。12，1。45)，P＜0。001]、抗β2糖蛋白 Ⅰ 抗体转阴率[RR=1。31，95％CI(1。12，1。52)，P＜0。001]，显著降低早期(＜10周)流产率[RR=0。31，95％CI(0。10，0。93)，P=0。04]。但在降低早产率、晚期(＞10周)流产率及先兆子痫发生率方面，2组差异无统计学意义(P＞0。05)。安全性分析，2项研究描述了 HCQ不良反应包括皮肤反应和眼睛干涩，症状均轻微;3项RCT比较2组患者不良反应发生率，HCQ组低于对照组[RR=0。40，95％CI(0。25，0。66)，P＜0。001]，2组均无严重不良反应发生。敏感性分析显示，结果稳健可靠。GRADE评价结果显示，本研究纳入指标的证据质量为低或极低级，弱推荐。结论 HCQ能显著提高OAPS活产率及抗磷脂抗体转阴率，降低10周前胎儿流产率，不良反应较少，但对降低早产、10周后胎儿流产及先兆子痫发生率证据不足。由于受纳入研究的数量和质量的限制，上述结论尚需更多高质量研究予以验证。
Efficacy and safety of hydroxychloroquine in the treatment of obstetric antiphospholipid syndrome:a Meta-analysis
Objective To systematically evaluate the efficacy and safety of hydroxychloroquine(HCQ)in obstetric antiphospholipid syndrome(OAPS).Methods PubMed,Embase,Cochrane Library,Web of Science,SinoMed,Wanfang Data,CNKI,and VIP databases were searched electronically to collect clinical research on HCQ treatment for OAPS from inception to January 31,2023.Two researchers independently screened the literature,extracted data,and assessed the risk of bias of the included studies,Meta-analysis and GRADE evaluation were performed using RevMan 5.4 software and GRADE Profile 3.6 softwares.Results Five cohort studies and three randomized controlled trias(RCTs)were included,with a total of 644 OAPS patients(732 pregnancies).The results of Meta-analysis showed that compared with conventional treatment,HCQ supplementation significantly increased the live birth rate of OAPS(RR=1.29,95％CI 1.10 to 1.51,P=0.001),the negative conversion rate of lupus anticoagulant(RR=1.29,95％CI 1.13 to 1.47,P＜0.001),the anticardiolipin antibody negative conversion rate(RR=1.27,95％CI 1.12 to 1.45,P＜0.001)and the anti-β2 glycoprotein I antibody negative conversion rate(RR=1.31,95％CI 1.12 to 1.52,P＜0.001),the rate of early abortion(＜10 weeks)was significantly reduced(RR=0.31,95％CI 0.10 to 0.93,P=0.04).However,there was no significant difference between the two groups in reducing the rate of premature birth,late abortion(＞10 weeks)and the incidence of preeclampsia(P＞0.05).In terms of safety analysis,two studies described HCQ adverse effects including skin reactions and dry eyes,symptoms are mild.Three RCTs were used to compare the incidence of adverse reactions between the two groups,the incidence of adverse reaction of HCQ group was lower than that of control group(RR=0.40,95％CI 0.25 to 0.66,P＜0.001),and no serious adverse reactions occurred in both groups.The sensitivity analysis results were robust and reliable.The results of GRADE evaluation showed that the quality of index evidence included in this study were low or very low,with weak recommendations.Conclusion HCQ can significantly improve the live birth rate of OAPS and the negative conversion rate of antiphospholipid antibody,and reduce the fetal abortion rate before 10 weeks with fewer adverse reactions,but there is insufficient evidence to reduce the incidence of premature birth,fetal abortion after 10 weeks and preeclampsia.Due to the limited number and quality of included studies,the above conclusions need to be confirmed by more high-quality studies.
万方数据
维普
