GRAND-4: the German retrospective analysis of long-term persistence in women with osteoporosis treated with bisphosphonates or denosumab

Abstract

SummaryThis retrospective database study assessed 2-year persistence with bisphosphonates or denosumab in a large German cohort of women with a first-time prescription for osteoporosis treatment. Compared with intravenous or oral bisphosphonates, 2-year persistence was 1.5–2 times higher and risk of discontinuation was significantly lower (P < 0.0001) with denosumab.IntroductionPersistence with osteoporosis therapies is critical for fracture risk reduction. Detailed data on long-term persistence (≥2 years) with bisphosphonates and denosumab are sparse.MethodsFrom the German IMS® database, we included women aged 40 years or older with a first-time prescription for bisphosphonates or denosumab between July 2010 and August 2014; patients were followed up until December 2014. The main outcome was treatment discontinuation, with a 60-day permissible gap between filled prescriptions. Two-year persistence was estimated using Kaplan–Meier survival curves, with treatment discontinuation as the failure event. Denosumab was compared with intravenous (i.v.) and oral bisphosphonates separately. Cox proportional hazard ratios (HRs) for the 2-year risk of discontinuation were calculated, with adjustment for age, physician specialty, health insurance status, and previous medication use.ResultsTwo-year persistence with denosumab was significantly higher than with i.v. or oral bisphosphonates (39.8 % [n = 21,154] vs 20.9 % [i.v. ibandronate; n = 20,472] and 24.8 % [i.v. zoledronic acid; n = 3966] and 16.7–17.5 % [oral bisphosphonates; n = 114,401]; all P < 0.001). Patients receiving i.v. ibandronate, i.v. zoledronic acid, or oral bisphosphonates had a significantly increased risk of treatment discontinuation than did those receiving denosumab (HR = 1.65, 1.28, and 1.96–2.02, respectively; all P < 0.0001).ConclusionsTwo-year persistence with denosumab was 1.5–2 times higher than with i.v. or oral bisphosphonates, and risk of discontinuation was significantly lower with denosumab than with bisphosphonates. A more detailed understanding of factors affecting medication-taking behavior may improve persistence and thereby reduce rates of fracture.

Persistence and compliance with osteoporosis therapies among postmenopausal women in the UK Clinical Practice Research Datalink

“…Previous persistence studies of denosumab covering the USA, Canada and several European countries excluding the UK have reported persistence at 12 months of 55.9-99.1% and at 24 months of 34.8-99.5% [24][25][26][27][28][29][30][31][32][33][34][35]. In contrast, for other parenteral therapies, the previous studies reported persistence at 12 months of 33.8-74.5%, and for oral therapies reported 10-78% [21,28].…”

Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium

“…In German and Swedish studies, persistence with denosumab was substantially higher than that seen with intravenous or oral bisphosphonates [13, 14]; in a Hungarian study, persistence was considerably lower with daily, weekly, and monthly treatments (10–18%) than with 6-monthly denosumab [15]. …”

“…Several studies have shown that younger age, specifically individuals less than 60 years old versus older age, is associated with lower persistence and adherence [13, 16, 18, 19]. While one study found no association between age and persistence [14], others have reported older age to be associated with lower persistence [17].…”

Can adverse effects of glucocorticoid therapy be prevented and treated?

“…A recent meta-analysis showed no significant difference in safety and reduction of fracture risk between denosumab and bisphosphonate therapy although higher gains in BMD were obtained with denosumab [44]. More advantages of denosumab are the safety of the drug in patients with renal insufficiency and the lower risk of discontinuation [45]. Effects of denosumab up to 8 years of treatment are promising with continuing gains in BMD [46].…”