SummaryThe objectives of this study were to estimate persistence with denosumab and put these results in context by conducting a review of persistence with oral bisphosphonates. Persistence with denosumab was found to be higher than with oral bisphosphonates.PurposeThis study had two objectives: to analyse persistence in Swedish women initiating denosumab for treatment of postmenopausal osteoporosis (PMO) and to put these findings in context by conducting a literature review and meta-analysis of persistence data for oral bisphosphonates.MethodsThe study used the Swedish Prescribed Drug Register and included women aged at least 50 years initiating denosumab between May 2010 and July 2012. One injection of denosumab was defined as 6-month persistence. Women were considered persistent for another 6 months if they filled their next prescription within 6 months + 56 days and survival analysis applied to the data. A literature search was conducted in PubMed to identify retrospective studies of persistence with oral bisphosphonates and pooled persistence estimates were calculated using a random-effects model.ResultsThe study identified 2,315 women who were incident denosumab users. Mean age was 74 years and 61 % had been previously treated for PMO. At 12 and 24 months, persistence with denosumab was 83 % (95 % CI, 81–84 %) and 62 % (95 % CI, 60–65 %), respectively. The literature search identified 40 articles for inclusion in the meta-analysis. At 12 and 24 months, persistence with oral bisphosphonates ranged from 10 % to 78 % and from 16 % to 46 %, with pooled estimates of 45 % and 30 %, respectively.ConclusionThese data from the Swedish Prescribed Drug Register and literature review suggest that persistence was higher with denosumab than with oral bisphosphonates.

This study assessed persistence and compliance with anti-osteoporosis therapies, and associations between compliance and clinical outcomes (fracture, fracture-related hospitalization and death), in Hungarian women with postmenopausal osteoporosis. The study used the Hungarian National Health Insurance Fund Administration database and included women with PMO aged at least 50 years, for whom a prescription for anti-osteoporosis medication had been filled between 1 January 2004 and 31 December 2013 (index event). Persistence (prescription refilled within 8 weeks of the end of the previous supply) was evaluated over 2 years; good compliance (medication possession ratio ≥ 80 %) was evaluated at 1 year. Associations between compliance and clinical outcomes (data collected for up to 6 years) were assessed with adjustment for baseline covariates. A total of 296,300 women met the inclusion criteria (524,798 index events). Persistence and compliance were higher for less frequent and parenteral therapies (1- and 2-year persistence: half-yearly [parenteral] vs. daily/weekly/monthly [oral and parenteral], 81 and 38 % vs. 21-34 and 10-18 %, respectively; parenteral vs. oral, 75 and 36 % vs. 32 and 16 %; good compliance: half-yearly vs. daily/weekly/monthly, 70 vs. 24-39 %; parenteral vs. oral 78 vs. 36 %). Good compliance significantly reduced the risks of fracture, fracture-related hospitalization and death (relative risk vs. non-compliance [95 % confidence interval]: 0.77 [0.70-0.84], 0.72 [0.62-0.85] and 0.57 [0.51-0.64], respectively; P < 0.01). Improving compliance through long-interval parenteral therapies may result in clinical benefits for patients.

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.

SummaryPersistence with osteoporosis therapy is critical for fracture risk reduction. This observational study evaluated medication-taking behaviour of women with postmenopausal osteoporosis receiving denosumab or oral ibandronate in real-world clinical practice in Bulgaria. Compared with ibandronate, densoumab was associated with a lower discontinuation rate and greater increases in bone mineral density.PurposePersistence with osteoporosis therapy is critical for fracture risk reduction and the effectiveness of such treatments may be reduced by low persistence. Alternative therapies such as denosumab may improve persistence. This study aimed to describe medication-taking behaviour in women with osteoporosis, prescribed denosumab or oral ibandronate, in Bulgarian clinical practice.MethodsThis retrospective, observational, multicentre chart review (with up to 24 months follow-up) enrolled postmenopausal women initiating 6-monthly denosumab injection or monthly oral ibandronate treatment for osteoporosis between 1 October 2011 and 30 September 2012.ResultsOverall, 441 women were enrolled (224 had initiated denosumab, 217 had initiated ibandronate). At baseline, more women in the denosumab group than in the ibandronate group had a previous fracture (25.5 vs 17.5%; p = 0.043) and past exposure to osteoporosis therapy (19.6 vs 12.0%; p = 0.028). At 24 months, 4.5% of women receiving denosumab had discontinued therapy compared with 56.2% of women receiving ibandronate. Median time to discontinuation was longer in the denosumab group (729 days; interquartile range (IQR), 728.3–729.0) than in the ibandronate group (367 days; IQR, 354.0–484.8; p < 0.001). At 24 months, there were significantly greater changes in BMD T-scores at the lumbar spine (p < 0.001) and femoral neck (p < 0.001) in patients receiving denosumab than in those receiving ibandronate. At 24 months, persistence with denosumab was 98.7%.ConclusionThis real-world study demonstrates there is a low discontinuation rate and high persistence with denosumab. Denosumab was associated with greater BMD increases than ibandronate, which could reduce fracture risk.

Compliance to osteoporosis drugs is frequently very low, leading to an increased fracture risk. We investigated the factors associated with fracture risk in women with postmenopausal osteoporosis (PMO) in Hungary, with a focus on compliance. MethOds: This retrospective analysis of data from the National Health Insurance Fund Administration included women aged ≥ 50 years with a diagnosis of osteoporosis (ICD-10 codes, M80 or 81), who started an osteoporosis drug prescription between Jan 2004-Dec 2012 (index event) and had a 13-month non-treatment period prior to this prescription. The relationship between all factors (covariates) and fracture risk was assessed using a dynamic Cox regression model and Andersen-Gill analysis, estimating 95% confidence intervals. Compliance was measured using the medication possession ratio (MPR); MPR≥ 80% at 1 year was considered compliant. Results: A total of 181,239 patients matched the inclusion criteria; 40.4% of patients were > 70 years old and 12.2% had prior fractures in the 36-month period before each index date. Compliant patients had a 35% (RR= 0.65, CI= 0.59-0.72) fracture risk reduction versus non-compliant patients. Patients aged 70-79 years, and > 80 years, had an increased fracture risk of 71% (RR= 1.71, CI= 1.54-1.90) and 118% (RR= 2.18, CI= 1.94-2.46), respectively, compared to patients aged 50-60 years. Prior fractures were associated with a 32% increased risk of one new fracture (RR= 1.32, CI= 1.18-1.49), and with a 90% increased fracture risk (RR= 1.90, CI= 1.64-2.19) in patients with 2+ prior fractures, respectively, compared to patients with no prior fractures. There was also a relationship between any co-medication and fracture risk, with a 12% (RR= 1.12, CI= 1.03-1.22) increase with one co-medication and an 11% (RR= 1.11, CI= 1.01-1.21) increase with 2+ comedications compared to none. cOnclusiOns: Compliance was associated with protection against fracture (reduction of relative fracture risk). However, age, any co-medication and prior fractures were associated with an increased relative risk of fracture.