Ye Shenglong, Zhao Xueqing, Liu Yuanying, Ma Yue, Wang Yongqing, Zhao Jinxia
Department of Obstetrics and Gynaecology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, 100191, Beijing, People's Republic of China.
Department of Rheumatology and Immunology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, 100191, Beijing, People's Republic of China.
Clin Rheumatol. 2023 Apr;42(4):1137-1150. doi: 10.1007/s10067-022-06462-y. Epub 2022 Dec 12.
This study was conducted to analyse the medication indications of hydroxychloroquine (HCQ) and to explore the clinical characteristics and perinatal outcomes of pregnancy in women with autoimmune abnormalities. The value of HCQ against placental dysfunction-related pregnancy outcomes in people with autoimmune abnormalities was also explored.
① To collect HCQ application cases during pregnancy who were hospitalized and delivered from 2016 to 2020. The classification and distribution of HCQ indications were analysed. The characteristics of cases and pregnancy outcomes were discussed. ② To include pregnancy combined with autoimmune abnormalities population during the period. Demographic information, clinical characteristics, classification, medication time frame, and pregnancy outcomes were discussed.
① There were 741 cases of HCQ use during pregnancy. Classification by drug indication was as follows: 257 cases (34.68%) had clear indications for autoimmune diseases. There were 359 controversial cases, as follows: 140 (18.89%) cases of antiphospholipid syndrome and 219 (29.55%) cases of autoantibody-positive cases who had no clear drug indication and also used HCQ during pregnancy. No indications were found for 125 cases (16.87%), without autoimmune abnormalities and empirical medication of HCQ during pregnancy. ② In 853 pregnancies with autoimmune abnormalities, women with systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease had clear indications for HCQ. The proportions of HCQ applied during pregnancy were 86.67%, 85.71%, 73.53%, and 75.00%. The start of medication before pregnancy only accounted for 74.44%, 65.31%, 64.71%, and 43.38%. ③ Medication indicated antiphospholipid syndrome and simple autoantibody-positive cases in the controversial population. The proportions of cases in which HCQ was used during pregnancy were 74.47% (140/188) and 64.79% (219/338). Application of HCQ during pregnancy significantly reduced pre-eclampsia (19.8% vs. 8.91%, P < 0.001), early-onset pre-eclampsia (7.78% vs. 2.51%, P = 0.007), and pregnancy loss during the middle and late pregnancy stages (2.99% vs. 0.56%, P = 0.036) in this controversial population.
Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. The strength of standardized and specialist management are needed in populations with clear HCQ indications. HCQ-indicated controversial population should avoid overdiagnosis and guard against the potential risks of combined anticoagulation and glucocorticoid therapy. The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. HCQ application may alleviate the incidence of adverse pregnancy outcomes in this population. Key Points •The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. •Our work have discovered the unique value of HCQ in improving placental dysfunction diseases in autoimmune abnormal cases, not just in AID such as SLE, SS, UTCD, and RA. •HCQ is a potential drug option for autoimmune abnormalities to improve placental function, by providing synergistic prevention and treatment of these disorders, not just single target of antispasmodic, anti-hypertensive, and circulatory improvement. •Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. However, the strength of standardized and specialist management are needed in populations with clear HCQ indications.
本研究旨在分析羟氯喹（HCQ）的用药指征，探讨自身免疫异常女性妊娠的临床特征及围产期结局。同时还探讨了HCQ对自身免疫异常人群中与胎盘功能障碍相关妊娠结局的价值。
①收集2016年至2020年期间住院分娩的孕期应用HCQ的病例。分析HCQ指征的分类及分布情况，讨论病例特征及妊娠结局。②纳入同期合并自身免疫异常的妊娠人群，讨论人口统计学信息、临床特征、分类、用药时间及妊娠结局。
①孕期应用HCQ共741例。按药物指征分类如下：自身免疫性疾病有明确指征者257例（34.68%）。有359例存在争议，其中抗磷脂综合征140例（18.89%），自身抗体阳性但无明确药物指征且孕期应用HCQ者219例（29.55%）。125例（16.87%）无指征，即孕期无自身免疫异常却经验性应用HCQ。②在853例合并自身免疫异常的妊娠中，系统性红斑狼疮、干燥综合征、类风湿关节炎及未分化结缔组织病女性应用HCQ有明确指征。孕期应用HCQ的比例分别为86.67%、85.71%、73.53%和75.00%。孕前开始用药的仅占74.44%、65.31%、64.71%和43.38%。③有争议人群中抗磷脂综合征及单纯自身抗体阳性病例用药情况，孕期应用HCQ的比例分别为74.47%（140/188）和64.79%（219/338）。在该有争议人群中，孕期应用HCQ显著降低了子痫前期（19.8% vs. 8.91%，P＜0.001）、早发型子痫前期（7.78% vs. 2.51%，P = 0.007）及孕中晚期流产（2.99% vs. 0.56%，P = 0.036）的发生率。
孕期HCQ经验性、指征过度甚至无指征使用情况常见。有明确HCQ指征的人群需要规范及专科管理。有争议的HCQ指征人群应避免过度诊断，警惕联合抗凝及糖皮质激素治疗的潜在风险。自身免疫异常人群胎盘功能障碍疾病发生率增加，应用HCQ可能降低该人群不良妊娠结局的发生率。要点 •自身免疫异常人群胎盘功能障碍疾病发生率增加。•我们的研究发现HCQ在改善自身免疫异常病例中的胎盘功能障碍疾病方面具有独特价值，不仅适用于系统性红斑狼疮、干燥综合征、未分化结缔组织病及类风湿关节炎等自身免疫性疾病。•HCQ是改善自身免疫异常胎盘功能的潜在药物选择，通过协同防治这些疾病，而非单纯抗痉挛、降压及改善循环的单一靶点作用。•孕期HCQ经验性、指征过度甚至无指征使用情况常见。然而，有明确HCQ指征的人群需要规范及专科管理。
