School of Dentistry (Wu), University of Leeds; Leeds Institute for Data Analytics (Keeley, Morgan, Pujades-Rodriguez), University of Leeds, Leeds, UK; Arthritis Research UK Primary Care Centre (Mallen), University of Keele, Staffordshire, UK; Leeds Institute of Cardiovascular and Metabolic Medicine (Morgan), School of Medicine, University of Leeds; NIHR Leeds Biomedical Research Centre (Morgan), Leeds Teaching Hospitals NHS Trust; Leeds Institute of Health Sciences (Pujades-Rodriguez), School of Medicine, University of Leeds, Leeds, UK.
School of Dentistry (Wu), University of Leeds; Leeds Institute for Data Analytics (Keeley, Morgan, Pujades-Rodriguez), University of Leeds, Leeds, UK; Arthritis Research UK Primary Care Centre (Mallen), University of Keele, Staffordshire, UK; Leeds Institute of Cardiovascular and Metabolic Medicine (Morgan), School of Medicine, University of Leeds; NIHR Leeds Biomedical Research Centre (Morgan), Leeds Teaching Hospitals NHS Trust; Leeds Institute of Health Sciences (Pujades-Rodriguez), School of Medicine, University of Leeds, Leeds, UK
CMAJ. 2019 Jun 24;191(25):E680-E688. doi: 10.1503/cmaj.190178.
Most patients with polymyalgia rheumatica or giant cell arteritis are treated with glucocorticoid therapy in primary care. We estimated dose-response risks of infection for this population in England.
We conducted a retrospective record-linkage study involving a cohort of people with polymyalgia rheumatica or giant cell arteritis registered in family practices across England (1998-2017). Estimates of first occurring infection per level of time-variant current and cumulative dose were obtained using Kaplan-Meier methods and multilevel proportional-hazards Cox models.
Of 39 938 patients attending 389 family practices, 22 234 (55.7%) had at least 1 infection over a median follow-up period of 4.8 years, with 5937 (26.7%) requiring hospital admission and 1616 (7.3%) dying within 7 days of diagnosis. Cumulative risks of all-cause infection were 18.3% (95% confidence interval [CI] 17.9%-18.7%) at 1 year, 54.7% (95% CI 54.1%-55.2%) at 5 years and 76.9% (95% CI 76.2%-77.5%) at 10 years. Lower respiratory tract infections, conjunctivitis and herpes zoster were the most commonly diagnosed infections. The increases in adjusted hazard ratios (HRs) for all-cause infection per 5 mg prednisolone-equivalent daily dose increase and per 1000 mg cumulative dose increase in the last year from the patient's end date of follow-up were 1.13 (95% CI 1.12-1.14) and 1.50 (95% CI 1.49-1.52), respectively. Adjusted HRs associated with periods of current glucocorticoid versus no glucocorticoid use ranged from 1.48 (95% CI 1.39-1.57) for fungal to 1.70 (95% CI 1.60-1.80) for bacterial infection. Stepwise dose-related associations were found for bacterial, viral, parasitic and fungal infections, irrespective of patient age, duration of underlying chronic disease and baseline vaccination status.
We quantified the excess risk of all-cause, bacterial, viral, parasitic and fungal infection conferred by oral glucocorticoids in people with polymyalgia rheumatica or giant cell arteritis and found strong dose responses for all types, even at daily doses of less than 5 mg prednisolone.
大多数巨细胞动脉炎或多发性肌炎患者在初级保健中接受糖皮质激素治疗。我们估计了英国该人群感染的剂量反应风险。
我们进行了一项回顾性记录链接研究，涉及英格兰各地家庭诊所登记的巨细胞动脉炎或多发性肌炎患者队列（1998-2017 年）。使用 Kaplan-Meier 方法和多水平比例风险 Cox 模型获得了每级时间变化的当前剂量和累积剂量的首次发生感染的估计值。
在接受 389 家诊所治疗的 39938 名患者中，22234 名（55.7%）在中位随访 4.8 年内至少发生了 1 次感染，其中 5937 名（26.7%）需要住院治疗，1616 名（7.3%）在诊断后 7 天内死亡。所有病因感染的累积风险在 1 年时为 18.3%（95%置信区间 [CI] 17.9%-18.7%），在 5 年时为 54.7%（95% CI 54.1%-55.2%），在 10 年时为 76.9%（95% CI 76.2%-77.5%）。下呼吸道感染、结膜炎和带状疱疹是最常见的诊断感染。从患者随访结束日期的最后一年开始，每增加 5 毫克泼尼松等效日剂量和每增加 1000 毫克累积剂量，调整后的全因感染风险比（HR）分别增加 1.13（95% CI 1.12-1.14）和 1.50（95% CI 1.49-1.52）。与无糖皮质激素使用相比，当前糖皮质激素使用期间与真菌感染（95% CI 1.48-1.39）相关的调整 HR 范围为 1.48（95% CI 1.39-1.57），与细菌感染（95% CI 1.60-1.80）相关的调整 HR 范围为 1.70（95% CI 1.60-1.80）。无论患者年龄、潜在慢性疾病持续时间和基线疫苗接种状况如何，都发现了与细菌、病毒、寄生虫和真菌感染相关的逐步剂量相关关联。
我们量化了口服糖皮质激素治疗巨细胞动脉炎或多发性肌炎患者的全因、细菌、病毒、寄生虫和真菌感染的风险，并发现所有类型的感染都存在强烈的剂量反应，即使每日泼尼松剂量低于 5 毫克。
