风湿病界对最近的监管警告表示关注,因为HCQ在2019年冠状病毒疾病大流行中使用可能导致急性精神病事件。我们的目的是研究是否存在偶发抑郁症的风险,用于RA的与HCQ相关的自杀意念或精神病。
我们使用来自10个来源和3个国家(德国,英国和美国)。年龄≥18岁并开始HCQ的RA患者与开始SSZ(主动比较)进行了比较,并在短期(30天)和长期(治疗)进行了随访。研究结果包括抑郁症,自杀/自杀意念和精神病住院。使用使用阴性对照结果的倾向评分分层和校准来解决混杂问题。拟合Cox模型以估计数据库特定的校准风险比(HR),在I2<40%的情况下合并估计值。
HCQ和SSZ共有918144和290383个用户,分别,包括在内。短期使用HCQ(与SSZ相比)未观察到一致的精神病事件风险,抑郁症的荟萃分析HR为0.96(95%CI0.79,1.16),自杀/自杀意念为0.94(95%CI0.49,1.77),精神病为1.03(95%CI0.66,1.60)。没有看到持续的长期风险,抑郁症的荟萃分析HR为0.94(95%CI0.71,1.26),自杀/自杀意念为0.77(95%CI0.56,1.07),精神病为0.99(95%CI0.72,1.35)。
用于治疗RA的HCQ似乎不会增加抑郁症的风险,与SSZ相比,自杀/自杀意念或精神病。短期或长期均未见效果。以更高的剂量使用或用于不同的适应症需要进一步研究。
在欧盟PAS注册(参考号EUPAS34497;http://www。encepp.eu/encepp/viewResource。htm?id=34498)。完整的研究协议和分析源代码可以在https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2上找到。
Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA.
We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%.
A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis.
HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation.
Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.