Risk of Serious Infection With Low-dose Glucocorticoids in Patients With Rheumatoid Arthritis: An Instrumental Variable Analysis.
Risk of Serious Infection With Low-dose Glucocorticoids in Patients With Rheumatoid Arthritis: An Instrumental Variable Analysis.
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DOI：
10.1097/ede.0000000000001422
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发表时间：
2022-01-01
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影响因子：
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通讯作者：
Baker JF
中科院分区：
文献类型：
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作者：
George MD;Hsu JY;Hennessy S;Chen L;Xie F;Curtis JR;Baker JF
小剂量糖皮质激素通常用于类风湿关节炎(RA)的治疗。观察性研究发现，与小剂量糖皮质激素相关的严重感染风险增加，但对残留混杂的担忧依然存在。使用2006年至2015年的医疗保险数据，我们确定了接受稳定免疫调节治疗的成年RA患者，为期6个月，不接受糖皮质激素或≤5 mg/天。我们使用供应商对糖皮质激素的偏好作为辅助变量(IV)来评估小剂量糖皮质激素使用与需要住院的感染风险之间的关联，使用原因特定的比例风险模型。我们在120,656名患者中确定了163,603次合格治疗。有25,373/81,802(31.0%)的风湿科医生看过对糖皮质激素的提供者偏好较低的患者，而36,087/81,801(44.1%)的风湿科医生看过的患者对糖皮质激素的提供者偏好较高(调整后的OR1.81，95%可信区间为1.77-1.84)，使用糖皮质激素≤5 mg/天。慢性阻塞性肺疾病、阿片类药物、抗生素、既往急诊科就诊、住院和需要住院的感染在暴露方面不平衡，但在IV方面不平衡。在未接触糖皮质激素的患者中，需要住院的感染发生率为8.0/100人年，而在暴露于糖皮质激素的患者中，需要住院的感染发生率为11.7/100人年。来自IV分析的糖皮质激素与需要住院的感染之间的关联[HR 1.26(1.02-1.56)]与标准多变量模型的结果[HR 1.24(1.21-1.28)]相似。在接受稳定免疫调节治疗的RA患者中，基于提供者偏好的IV分析表明，与传统分析类似，与小剂量糖皮质激素相关的需要住院的感染风险增加。
Low-dose glucocorticoids are commonly used in the treatment of rheumatoid arthritis (RA). Observational studies have found increased risk of serious infection associated with low-dose glucocorticoids, but concerns about residual confounding remain. We identified adults with RA on stable immunomodulatory therapy for >6 months receiving no glucocorticoids or ≤5mg/day using Medicare data from 2006–2015. We used provider preference for glucocorticoids as an instrumental variable (IV) to assess associations between low-dose glucocorticoid use and risk of infection requiring hospitalization using a cause-specific proportional hazards model. We identified 163,603 qualifying treatment episodes among 120,656 patients. Glucocorticoids ≤5mg/day were used by 25,373/81,802 (31.0%) of patients seen by a rheumatologist with low provider preference for glucocorticoids and by 36,087/81,801 (44.1%) of patients seen by a rheumatologist with high provider preference for glucocorticoids (adjusted OR 1.81, 95% CI 1.77–1.84 for association between provider preference and glucocorticoids). Chronic obstructive pulmonary disease, opioids, antibiotics, previous emergency department visits, hospitalizations, and infections requiring hospitalization infections were unbalanced with regard to exposure but not to the IV. The incidence of infection requiring hospitalization was 8.0/100 person–years among patients unexposed to glucocorticoids versus 11.7/100 person–years among those exposed. The association between glucocorticoids and infection requiring hospitalization from IV analysis [HR 1.26 (1.02–1.56)] was similar to results from a standard multivariable model [HR 1.24 (1.21–1.28)]. Among patients with RA on stable immunomodulatory therapy, IV analysis based on provider preference demonstrated an increased risk of infection requiring hospitalization associated with low-dose glucocorticoids, similar to a traditional analysis.