Impact of risk minimisation measures on the use of strontium ranelate in Europe:​ a multi-national cohort study in 5 EU countries by the EU-ADR alliance

Berencsi, K.; Sami, A.; Ali, M. S.; Marinier, K.; Deltour, N.; Perez-Gutthann, S.; Pedersen, L.; Rijnbeek, P.; Van der Lei, J.; Lapi, F.; Simonetti, M.; Reyes, C.; Sturkenboom, M. C. J. M.; Prieto-Alhambra, D.

Affiliations

¹Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark

²Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK

³Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

⁴Department of Pharmacoepidemiology, Servier, Suresnes, France

⁵RTI Health Solutions, Barcelona, Spain

⁶Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands

⁷Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy

⁸GREMPAL Research Group, Idiap Jordi Gol Primary Care Research Institute and CIBERFes, Universitat Autonoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain

⁹Julius Global Health, University Medical Center, Utrecht, The Netherlands

¹⁰Botnar Research Centre, Oxford, UK

Abstract and keywords

Introduction: In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK). Participants: the database source populations were included for population-based analyses, and SR users for patient-level analyses. Intervention: New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy.

Methods: Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016).

Results: The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4–62.9) in the reference to 8.5 (8.5–8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4–7.4) to 0.2 (0.2–0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period.

Conclusions: Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.

Keywords: Pharmacoepidemiology; Risk minimisation measures; Strontium ranelate

Links

DOI: 10.1007/s00198-019-05181-6

PubMed: 32025756

WoS: 000515832100001

History

Received: 2019-06-19

Accepted: 2019-09-26

Online: 2019-11-06

Cited By (1)

Year	Entry
2020	Ali MS, Berencsi K, Marinier K, Deltour N, Perez-Guthann S, Pedersen L, Rijnbeek P, Lapi F, Simonetti M, Reyes C, Van der Lei J, Sturkenboom M, Prieto-Alhambra D. Comparative cardiovascular safety of strontium ranelate and bisphosphonates: a multi-database study in 5 EU countries by the EU-ADR alliance. Osteoporos Int. December 2020;31(12):2425-2438.