Real-world differences in denosumab persistence, reinitiation, and switching among cohorts of older adults in Canada and the United States

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.