From the Division of Rheumatology, University of Pennsylvania, Philadelphia, PA.
Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA.
Epidemiology. 2022 Jan 1;33(1):65-74. doi: 10.1097/EDE.0000000000001422.
Low-dose glucocorticoids are commonly used in the treatment of rheumatoid arthritis (RA). Observational studies have found an 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 ≤5 mg/day using Medicare data from 2006 to 2015. We used provider preference for glucocorticoids as an instrumental variable (IV) to assess associations between low-dose glucocorticoid use and the risk of infection requiring hospitalization using a cause-specific proportional hazards model.
We identified 163,603 qualifying treatment episodes among 120,656 patients. Glucocorticoids ≤5 mg/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 odds ratio 1.81, 95% confidence interval 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 (hazard ratio 1.26 [1.02-1.56]) was similar to results from a standard multivariable model (hazard ratio 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.
低剂量的糖皮质激素常用于治疗类风湿关节炎（RA）。观察性研究发现，低剂量糖皮质激素与严重感染风险增加相关，但仍存在残留混杂因素的担忧。
我们利用 2006 年至 2015 年期间的医疗保险数据，确定了正在接受稳定免疫调节治疗>6 个月且未接受糖皮质激素或≤5mg/天治疗的 RA 成年患者。我们使用糖皮质激素的提供者偏好作为工具变量（IV），通过特定病因的比例风险模型评估低剂量糖皮质激素使用与感染住院风险之间的关联。
在 120656 名患者中，我们确定了 163603 个符合条件的治疗周期。在糖皮质激素提供者偏好低的情况下，81802 名患者中有 25373 名（31.0%）患者使用≤5mg/天的糖皮质激素，而在糖皮质激素提供者偏好高的情况下，81801 名患者中有 36087 名（44.1%）患者使用（暴露于糖皮质激素和提供者偏好之间的关联的调整比值比为 1.81，95%置信区间为 1.77，1.84）。慢性阻塞性肺疾病、阿片类药物、抗生素、之前的急诊就诊、住院和需要住院治疗的感染在暴露方面不平衡，但在 IV 方面没有不平衡。未暴露于糖皮质激素的患者感染住院的发生率为 8.0/100 人年，而暴露于糖皮质激素的患者为 11.7/100 人年。基于 IV 分析的糖皮质激素与感染住院的关联（风险比 1.26[1.02-1.56]）与标准多变量模型的结果（风险比 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 分析显示，低剂量糖皮质激素与感染住院风险增加相关，与传统分析结果相似。
