The Risk and Risk Factors of Incident Hydroxychloroquine Retinopathy Among Long-Term Users

长期使用者发生羟氯喹视网膜病变的风险和危险因素

• 批准号: 9973207
• 负责人: HYON K CHOI
• 金额: $ 13.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-05 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9973207
• 关键词: Academy; Address; Adopted; Adverse event; Affect; American; Biological; Blinded; Body Weight; California; Clinical; Data; Disease; Dose; Dyslipidemias; Epidemiologist; Epidemiology; Etanercept; Guidelines; Hydroxychloroquine; Incidence; Incidence Study; Individual; Insulin Resistance; Modernization; Nephritis; Ophthalmology; Optical Coherence Tomography; Patient Noncompliance; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Physicians; Population; Positioning Attribute; Pregnancy Complications; Prevalence; Prevalence Study; Preventive measure; Reading; Recommendation; Records; Regimen; Reporting; Research Methodology; Research Personnel; Retina; Retinal Diseases; Rheumatism; Rheumatoid Arthritis; Rheumatology; Risk; Risk Factors; Safety; Screening procedure; Specialist; Survivors; System; Systemic Lupus Erythematosus; Textbooks; Therapeutic; Time; Vision; Visual Fields; Weight; Work; base; clinical practice; cohort; college; cost; cost effective; data access; evidence base; experience; high risk; illness length; improved; mortality; mortality risk; prevent; randomized trial; rheumatologist; screening; screening program; venous thromboembolism

Despite therapeutic advances in antirheumatic regimens, hydroxychloroquine (HCQ) is still near-universally recommended for systemic lupus erythematosus (SLE) patients. For example, following the NEJM trial, which showed that HCQ discontinuation led to a 2.5 times higher risk of SLE exacerbation, many studies have reported wide-ranging benefits of HCQ, including improved survival. Furthermore, HCQ is often used in the management of rheumatoid arthritis (RA) and other rheumatic conditions. The efficacy of triple therapy (which includes HCQ) in RA is proven to be similar to that of etanercept, while being much more cost-effective. HCQ is now being investigated in randomized trials as a preventive measure for RA among high-risk individuals. Although HCQ is generally well-tolerated, a critical long-term adverse event is vision-threatening toxic retinopathy. Historically, the risk was considered low (i.e., <2%). However, a recent large study (N=2,361 taking HCQ for ≥5 years) by our investigators found the prevalence of HCQ retinopathy to be 7.5% according to their review of spectral-domain optical coherence tomography (SDOCT) or visual field assessment (VFA) exams from 2,361 patients taking HCQ for >5 years. The prevalence correlated with HCQ dose and duration of use and was 10% within 10 years of HCQ use at a dose of >5mg/kg daily and rose to 40% after 20 years of use. These prevalence data have renewed serious concerns among patients and prescribing physicians alike and even led to a revision of the American Academy of Ophthalmology (AAO) (2016) and UK Royal College of Ophthalmology guidelines (2018). However, the prediction based on prevalence (as opposed to incidence) in this context can be substantially overestimating because prevalence depends on both incidence and disease duration, which is permanent in HCQ retinopathy cases. Furthermore, predictions based on survivors, as in prevalence studies, do not account for the competing risk of death (e.g., >2-fold increased mortality in SLE), further leading to risk overestimation. Adopting such overestimation in clinical guidelines creates false concerns, potentially worsening under-use of HCQ. Moreover, factors that increase prevalence may do so not by increasing the occurrence of the condition but by increasing the duration of the condition. Therefore, correlates of prevalent cases may not be true risk factors for HCQ retinopathy. Accurate risk data derived from incident cases is crucial for evidence- based clinical guidelines. In this study, AAO guideline retinal specialists, rheumatologists, and epidemiologists will work together to determine the risk of incident HCQ retinopathy and its risk factors by reviewing annual VFA and SDOCT exams in a cohort of > 6,000 HCQ long-term users (i.e., ≥ 5 years), starting from Year 5 of use, through centralized blinded readings. This incidence study will directly build upon the recent prevalence study experience and system-wide HCQ retinopathy screening data of Kaiser Permanente Northern California. With our collective expertise in pharmacoepidemiology, HCQ retinopathy, and rheumatology, combined with uniquely fitting data access, we are in an unparalleled position to address this key issue in a timely manner.

尽管抗风湿疗法取得了进展，但羟氯喹(Hcq)仍然几乎是普遍存在的。 推荐给系统性红斑狼疮(SLE)患者。例如，在NEJM审判之后， 许多研究表明，停用氢氯喹酮会导致系统性红斑狼疮恶化的风险增加2.5倍 HCQ的广泛好处，包括提高存活率。此外，在管理中还经常使用HCQ 类风湿性关节炎(RA)和其他风湿性疾病。三联疗法(包括HCQ)的疗效 在RA中被证明与依那西普相似，但更具成本效益。HCQ现在正在进行 在随机试验中进行研究，作为高危人群中RA的预防措施。虽然HCQ是 一般来说，耐受性良好，一个关键的长期不良事件是威胁视力的中毒性视网膜病变。 从历史上看，风险被认为是低的(即2%)。然而，最近的一项大型研究(N=2,361)将HCQ用于≥5 年)，我们的研究人员发现HCQ视网膜病变的患病率为7.5% 2361例光谱域光学相干断层扫描(SDOCT)或视野评估(VFA)检查 服用HCQ 5年的患者。患病率与氢氯喹酮剂量和使用时间相关，为10% 在使用HCQ的10年内，每天服用5毫克/公斤，使用20年后上升到40%。这些流行率 数据再次引起了患者和处方医生的严重担忧，甚至导致了一项修订 美国眼科学会(AAO)(2016)和英国皇家眼科学院指南 (2018)。然而，在这种情况下，基于流行率(而不是发病率)的预测可以是 大大高估了，因为流行率取决于发病率和病程，这是 永久存在于HCQ视网膜病变病例中。此外，像在流行率研究中那样，基于幸存者的预测确实 不考虑相互竞争的死亡风险(例如，系统性红斑狼疮死亡率增加2倍)，进一步导致风险 高估了。在临床指南中采用这种高估会产生错误的担忧，可能会恶化 使用不充分的HCQ。此外，增加患病率的因素可能不是通过增加 而是通过增加条件的持续时间。因此，流行病例的相关性可能不会 是HCQ视网膜病变的真正危险因素。从事故案例中获得准确的风险数据对于证据至关重要- 以临床指南为基础。在这项研究中，AAO指导视网膜专家、风湿病专家和流行病学家 将通过每年一次的回顾，共同确定事件HCQ视网膜病变的风险及其风险因素 从第5年第5年开始，对6,000名长期使用HCQ(即≥5年)的用户进行VFA和SDOCT考试 使用，通过集中盲读。这项发病率研究将直接建立在最近的流行率基础上 北加州Kaiser Permanente的研究经验和全系统HCQ视网膜病变筛查数据。 凭借我们在药物流行病学、HCQ视网膜病变和风湿病方面的集体专业知识， 通过独一无二的数据访问，我们处于无与伦比的地位，能够及时解决这一关键问题。