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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

  • K. Berencsi
  • A. Sami
  • M.S. Ali
  • K. Marinier
  • N. Deltour
  • S. Perez-Guthann
  • L. Pedersen
  • P. Rijnbeek
  • J. Van der Lei
  • F. Lapi
  • M. Simonetti
  • C. Reyes
  • M.C.J.M. Sturkenboom
  • D. Prieto-AlhambraEmail author
Original Article

Abstract

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 

Notes

Funding information

This work was funded by Servier through a research grant to the EU-ADR Alliance. This work was partially supported by the NIHR Biomedical Research Centre, Oxford.

Compliance with ethical standards

Conflicts of interest

Karine Marinier is an employee of Servier. Nicolas Deltour is an employee of Servier. Susana Perez-Guthann received grants and consultation contracts from pharmaceutical companies including Servier for other regulatory safety studies and projects. Miriam CJM Sturkenboom, MCJMS, was co-coordinating the work from Erasmus University Medical Center. Daniel Prieto-Alhambra, DPA, is funded by the National Institute for Health Research Clinician Scientist award (CS-2013-13-012). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Lars Pedersen, Peter Rijnbeek, Johan Van der Lei, Francesco Lapi, Monica Simonetti, Carlen Reyes, Klara Berencsi, Arvind Sami and M Sanni Ali.

Disclaimer

The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  • K. Berencsi
    • 1
    • 2
  • A. Sami
    • 2
  • M.S. Ali
    • 2
    • 3
  • K. Marinier
    • 4
  • N. Deltour
    • 4
  • S. Perez-Guthann
    • 5
  • L. Pedersen
    • 1
  • P. Rijnbeek
    • 6
  • J. Van der Lei
    • 6
  • F. Lapi
    • 7
  • M. Simonetti
    • 7
  • C. Reyes
    • 8
  • M.C.J.M. Sturkenboom
    • 9
  • D. Prieto-Alhambra
    • 2
    • 8
    • 10
    Email author
  1. 1.Department of Clinical EpidemiologyAarhus UniversityAarhusDenmark
  2. 2.Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, NDORMSUniversity of OxfordOxfordUK
  3. 3.Faculty of Epidemiology and Population HealthLondon School of Hygiene and Tropical MedicineLondonUK
  4. 4.Department of PharmacoepidemiologyServierSuresnesFrance
  5. 5.RTI Health SolutionsBarcelonaSpain
  6. 6.Department of Medical InformaticsErasmus University Medical CenterRotterdamThe Netherlands
  7. 7.Health SearchItalian College of General Practitioners and Primary CareFlorenceItaly
  8. 8.GREMPAL Research Group, Idiap Jordi Gol Primary Care Research Institute and CIBERFesUniversitat Autonoma de Barcelona and Instituto de Salud Carlos IIIBarcelonaSpain
  9. 9.Julius Global HealthUniversity Medical CenterUtrechtThe Netherlands
  10. 10.Botnar Research CentreOxfordUK

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