Loss of treatment benefit due to low compliance with bisphosphonate therapy

Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit. Introduction: Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit. Methods: New female users of alendronate or risedronate between 1999-2004, aged ≥45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of ≥2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression. Results: The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR ≥90%. Conclusions: These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit

Validation of the adherence evaluation of osteoporosis treatment (ADEOS) questionnaire for osteoporotic post-menopausal women

SUMMARY: We developed and validated a specific 12-item questionnaire to evaluate adherence to oral antiresorptive medication by post-menopausal osteoporotic women in everyday practice. Over the following 9 months, an index of ≤16 was associated with an increase in the risk of treatment discontinuation of 1.69 and of 2.10 for new patients who had started treatment within the previous year. INTRODUCTION: Adherence to medication in osteoporosis is poor. The goal of this study was to develop and validate a disease-specific questionnaire to evaluate adherence to treatment of women with post-menopausal osteoporosis taking oral antiresorptive medication. METHODS: A prototype adherence questionnaire with 45 items developed from patient interview, literature review, and physician opinion was evaluated in a sample of 350 post-menopausal women with osteoporosis treated in primary care. Item responses were matched against scores on the Morisky Medication Adherence Scale (MMAS). The most discriminant items were retained in the final questionnaire. Concurrent and predictive validity were assessed. RESULTS: Twelve items were associated with MMAS score at a probability level of 0.05. These were retained in the final questionnaire which provided an adherence index ranging from 0 to 22. An index of ≥20 was associated with a high probability of persistence and an index ≤ 16 with a high probability of treatment discontinuation in the following 9 months. CONCLUSIONS: The ADEOS-12 is a simple patient-reported measure to determine adherence to osteoporosis treatments with good concurrent and discriminant validity. This is the first disease-specific adherence measure to have been developed for osteoporosis

Impact of EU regulatory label changes for diclofenac in people with cardiovascular disease in four countries:interrupted time series regression analysis

Objective: Due to cardiovascular safety concerns, the European Medicines Agency (EMA) recommended new contraindications and changes to product information for diclofenac across Europe in 2013. This study aims to measure their impact among targeted populations. Method: Quarterly interrupted time series regression (ITS) analyses of diclofenac initiation among cohorts with contraindications (congestive cardiac failure [CHF], ischaemic heart disease [IHD], peripheral arterial disease [PAD], cerebrovascular disease [CVD]) and cautions (hypertension, hyperlipidaemia, diabetes) from Denmark, the Netherlands, England and Scotland. Results: The regulatory action was associated with significant immediate absolute reductions in diclofenac initiation in all countries for IHD (Denmark −0.08%, 95%CI −0.13, −0.03; England −0.09%, 95%CI −0.13 to −0.06%; the Netherlands −1.84%, 95%CI −2.51 to −1.17%; Scotland −0.34%, 95%CI −0.38 to −0.30%), PAD and hyperlipidaemia, the Netherlands, England and Scotland for hypertension and diabetes, and England and Scotland for CHF and CVD. Post-intervention there was a significant negative trend in diclofenac initiation in the Netherlands for IHD (−0.12%, 95%CI −0.19 to −0.04), PAD (−0.13%, 95%CI −0.22 to −0.05), hypertension, hyperlipidaemia and diabetes, and in Scotland for CHF (−0.01%, 95%CI −0.02 to −0.007%), IHD (−0.017, 95%CI −0.02, −0.01%), PAD and hypertension. In England, diclofenac initiation rates fell less steeply. In Denmark changes were more strongly associated with the earlier EMA 2012 regulatory action. Conclusion: Although significant reductions in diclofenac initiation occurred, patients with contraindications continued to be prescribed diclofenac, the extent of which varied by country and target condition. Understanding reasons for such variation may help to guide the design or dissemination of future safety warnings

Trends in mortality, cardiovascular complications, and risk factors in type 2 diabetes

Background: Quality of diabetes care in the Netherlands ranked second in the Euro Diabetes Index 2014, but data on outcomes are lacking. We assessed trends in cardiovascular disease and mortality among type 2 diabetes (T2DM) patients in the context of risk factor control. Methods: Annual cohorts of adult T2DM patients were constructed from the PHARMO Database Network. Age-standardised mortality rates and incidence rates (IR) of hospitalisations for acute myocardial infarction (AMI), stroke, and congestive heart failure (CHF) were compared with a diabetes-free population matched on age, sex, and general practitioner. Life years lost (LYL) to T2DM or cardiovascular disease were determined by comparing life expectancy between matched groups. Proportions attaining glycated haemoglobin (HbAic), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) goals were assessed annually. Results: Among 53,602 T2DM patients, slight increases in IR between 2008 and 2016 were proportional to those in diabetes-free controls; on average T2DM increased the risk of mortality by 86%, hospitalisation for AMI 69%, stroke 57%, and CHF 185%. At age 55, LYL to T2DM averaged 3.5 years and established CVD added 1.8 years, irrespective of sex. HbAIc goal attainment increased from 58% to 65%, LDL-C from 56% to 65%, and systolic BP from 57% to 72%. Conclusion: Despite highly organised diabetes care, excess incident cardiovascular events and mortality due to T2DM did not decrease over the study period. Life expectancy of T2DM patients is significantly reduced and risk factor control is suboptimal. This suggests there is considerable room for improvement of diabetes care in the Netherlands