Hayes Kaleen N, Sendhil Selvam R, Aggarwal Sulbh, Zullo Andrew R, Berry Sarah D, Oganisian Arman, Adegboye Michael, Cadarette Suzanne M
Department of Health Services, Policy, and Practice, Center for Gerontology and Healthcare Research, Brown University School of Public Health, Providence, RI 02903, United States.
Department of Epidemiology, Brown University School of Public Health, Providence, RI 02903, United States.
JBMR Plus. 2025 Apr 11;9(6):ziaf061. doi: 10.1093/jbmrpl/ziaf061. eCollection 2025 Jun.
Denosumab is an injectable osteoporosis medication administered twice per year. Discontinuation of denosumab can result in rapid rebound fractures, but the evidence is limited on real-world persistence with denosumab. We conducted 2 parallel, population-based cohort studies leveraging (1) healthcare administrative data from Ontario, Canada (ON; 100% population) and (2) a 20% random sample of US Medicare beneficiaries (US). The first denosumab claim (US: 1/2010-12/2019; ON: 1/2012-12/2021) was identified using pharmacy claims (ON) and Medicare Parts D and B claims (US). Patients aged <66 yr, residing in long-term care (LTC), or with implausible data (eg, death before first claim) were excluded. We developed and applied an algorithm that used dosing and days between dispensations to clean denosumab claims. We assumed a days supply of 183 d for each dispensation and defined discontinuation as a 60-d gap in coverage. We estimated initial persistence, reinitiation, and switching to other osteoporosis medications using Kaplan-Meier estimators, censoring on death, disenrollment (US only), LTC admission, or study end (12/31/2022 [ON], 12/31/2020 [US]). We also estimated the monthly proportion of patients with an on-time denosumab dose to explore time trends. We identified 168 339 eligible individuals in ON (mean age = 78 yr; 90% female) and 97 595 in the US (mean age = 77 yr; 90% female). In ON, the median time to denosumab discontinuation was longer (median 2.3 yr [ON] vs 1.7 yr [US]; 3-yr persistence: 44% [ON] vs 31% [US]), and time to reinitiation was shorter (median = 0.5 yr [ON] vs 1.9 yr [US]). In both populations, around 10% switched to another osteoporosis medication. Women and those with prior oral bisphosphonate use had longer durations of denosumab treatment in ON but not in the US. The proportion persisting with on-time doses did not increase over time in the US or ON. Research to improve persistence with denosumab and optimize post-denosumab treatment is critical.
地诺单抗是一种每年注射两次的骨质疏松症药物。停用该药物可能导致快速的反弹性骨折，但关于地诺单抗在现实世界中的持续使用情况的证据有限。我们进行了两项平行的、基于人群的队列研究，利用（1）来自加拿大安大略省（ON；100%人口）的医疗保健管理数据，以及（2）美国医疗保险受益人的20%随机样本（US）。首次地诺单抗申请（美国：2010年1月至2019年12月；安大略省：2012年1月至2021年12月）通过药房申请（安大略省）以及美国医疗保险D部分和B部分的申请来确定。年龄小于66岁、居住在长期护理机构（LTC）或数据不可信（如首次申请前死亡）的患者被排除。我们开发并应用了一种算法，该算法利用给药剂量和配药间隔天数来清理地诺单抗申请。我们假设每次配药的供应天数为183天，并将停药定义为保险覆盖范围有60天的间隔。我们使用Kaplan-Meier估计量估计初始持续使用情况、重新开始使用情况以及改用其他骨质疏松症药物的情况，以死亡、退出保险（仅美国）、入住长期护理机构或研究结束（2022年12月31日[安大略省]，2020年12月31日[美国]）作为删失值。我们还估计了按时接受地诺单抗剂量治疗的患者每月的比例，以探索时间趋势。我们在安大略省确定了168339名符合条件的个体（平均年龄 = 78岁；90%为女性），在美国确定了97595名（平均年龄 = 77岁；90%为女性）。在安大略省，地诺单抗停药的中位时间更长（安大略省为2.3年，美国为1.7年；3年持续使用率：安大略省为44%，美国为31%），重新开始使用的时间更短（安大略省中位时间为0.5年，美国为1.9年）。在这两个人群中，约10%的人改用了另一种骨质疏松症药物。在安大略省，女性和之前使用过口服双膦酸盐的人接受地诺单抗治疗的时间更长，但在美国并非如此。在美国或安大略省，按时服药的持续比例并没有随着时间的推移而增加。开展研究以提高地诺单抗的持续使用情况并优化地诺单抗治疗后的处理至关重要。
