Skip to main content
SpringerLink
Log in

Adherence to Long-Term Interferon Beta-1b Injection Therapy in Patients with Multiple Sclerosis Using an Electronic Diary

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring long-term treatment, which is often hampered by non-adherence to self-applicable therapies, provoking continued disease activity and health care system burdens. This study assessed the influence of a personal digital assistant (PDA) with diary function (n = 339 patients) on persistence and adherence to an interferon beta treatment regimen in comparison to a paper patient diary (n = 330 patients).

Methods

Patients who recently started with subcutaneous injections of interferon beta-1b were recruited in this prospective, non-interventional, national cohort study for an observational period of 2 years after successful completion of the initial dose escalation.

Results

Therapy persistence as assessed by the drop-out rate within 104 weeks was about 50% in both study cohorts. In male patients, the drop-out rate was 10% lower when using a PDA compared to the non-PDA group. Use of a PDA with an injection reminder function increased adherence to the injection schedule (every other day) by a mean of 24.5 injections over 24 months in comparison to use of a PDA without injection reminder function.

Conclusion

Persistence in this study was in the published range of observational MS studies. Furthermore, in male patients continuation of therapy might be positively influenced by use of a PDA, and both female and male patients might benefit from an integrated reminder function. In conclusion, electronic diaries reminding patients of upcoming injections can promote an improved adherence to MS therapy.

Trial registration

ClinicalTrials.gov identifier: NCT00902135.

Funding

Bayer Vital GmbH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Steinman L. Immunology of relapse and remission in multiple sclerosis. Annu Rev Immunol. 2014;32:257–81.

    Article  CAS  PubMed  Google Scholar 

  2. Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014;89:225–40.

    Article  PubMed  Google Scholar 

  3. Lugaresi A, Rottoli MR, Patti F. Fostering adherence to injectable disease-modifying therapies in multiple sclerosis. Expert Rev Neurother. 2014;14:1029–42.

    Article  CAS  PubMed  Google Scholar 

  4. Klauer T, Zettl UK. Compliance, adherence, and the treatment of multiple sclerosis. J Neurol. 2008;255:87–92.

    Article  PubMed  Google Scholar 

  5. Steinberg SC, Faris RJ, Chang CF, Chan A, Tankersley MA. Impact of adherence to interferons in the treatment of multiple sclerosis: a non-experimental, retrospective, cohort study. Clin Drug Investig. 2010;30:89–100.

    Article  CAS  PubMed  Google Scholar 

  6. Treadaway K, Cutter G, Salter A, et al. Factors that influence adherence with disease-modifying therapy in MS. J Neurol. 2009;256:568–76.

    Article  PubMed  Google Scholar 

  7. Kern S, Reichmann H, Ziemssen T. Adherence to neurologic treatment. Lessons from multiple sclerosis. Nervenarzt. 2008;79:877–90.

    Article  CAS  PubMed  Google Scholar 

  8. Ivanova JI, Bergman RE, Birnbaum HG, Phillips AL, Stewart M, Meletiche DM. Impact of medication adherence to disease-modifying drugs on severe relapse, and direct and indirect costs among employees with multiple sclerosis in the US. J Med Econ. 2012;15:601–9.

    Article  CAS  PubMed  Google Scholar 

  9. Tremlett H, Van der Mei I, Pittas F, et al. Adherence to the immunomodulatory drugs for multiple sclerosis: contrasting factors affect stopping drug and missing doses. Pharmacoepidemiol Drug Saf. 2008;17:565–76.

    Article  PubMed  Google Scholar 

  10. Menzin J, Caon C, Nichols C, White LA, Friedman M, Pill MW. Narrative review of the literature on adherence to disease-modifying therapies among patients with multiple sclerosis. J Manag Care Pharm. 2013;19:S24–40.

    PubMed  Google Scholar 

  11. Bruce JM, Hancock LM, Lynch SG. Objective adherence monitoring in multiple sclerosis: initial validation and association with self-report. Mult Scler. 2010;16:112–20.

    Article  PubMed  Google Scholar 

  12. Goldberg J, Wolf A, Silberstein S, et al. Evaluation of an electronic diary as a diagnostic tool to study headache and premenstrual symptoms in migraineurs. Headache. 2007;47:384–96.

    PubMed  Google Scholar 

  13. Mondorf W, Siegmund B, Mahnel R, et al. Haemoassist–a hand-held electronic patient diary for haemophilia home care. Haemophilia. 2009;15:464–72.

    Article  CAS  PubMed  Google Scholar 

  14. Stone AA, Shiffman S, Schwartz JE, Broderick JE, Hufford MR. Patient compliance with paper and electronic diaries. Control Clin Trials. 2003;24:182–99.

    Article  PubMed  Google Scholar 

  15. Klein M, Mogles N, van Wissen A. Intelligent mobile support for therapy adherence and behavior change. J Biomed Inform. 2014;51:137–51.

    Article  PubMed  Google Scholar 

  16. Klasnja P, Pratt W. Healthcare in the pocket: mapping the space of mobile-phone health interventions. J Biomed Inform. 2012;45:184–98.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zettl UK, Bauer-Steinhusen U, Glaser T, Hechenbichler K, Limmroth V, Study Group. Evaluation of an electronic diary for improvement of adherence to interferon beta-1b in patients with multiple sclerosis: design and baseline results of an observational cohort study. BMC Neurol. 2013;13:117.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. PLoS Med. 2010;7:e1000251.

    Article  PubMed  PubMed Central  Google Scholar 

  19. McLeod TG, Ebbert JO, Lymp JF. Survey assessment of personal digital assistant use among trainees and attending physicians. J Am Med Inform Assoc. 2003;10:605–7.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Jokubaitis VG, Spelman T, Lechner-Scott J, et al. The Australian Multiple Sclerosis (MS) immunotherapy study: a prospective, multicentre study of drug utilisation using the MSBase platform. PLoS One. 2013;8:e59694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Milanese C, La Mantia L, Palumbo R, et al. A post-marketing study on interferon beta 1b and 1a treatment in relapsing-remitting multiple sclerosis: different response in drop-outs and treated patients. J Neurol Neurosurg Psychiatry. 2003;74:1689–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Meyniel C, Spelman T, Jokubaitis VG, et al. Country, sex, EDSS change and therapy choice independently predict treatment discontinuation in multiple sclerosis and clinically isolated syndrome. PLoS One. 2012;7:e38661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wong J, Gomes T, Mamdani M, Manno M, O’Connor PW. Adherence to multiple sclerosis disease-modifying therapies in Ontario is low. Can J Neurol Sci. 2011;38:429–33.

    Article  PubMed  Google Scholar 

  24. Portaccio E, Zipoli V, Siracusa G, Sorbi S, Amato MP. Long-term adherence to interferon beta therapy in relapsing-remitting multiple sclerosis. Eur Neurol. 2008;59:131–5.

    Article  CAS  PubMed  Google Scholar 

  25. Hansen K, Schüssel K, Kieble M, et al. Adherence to disease modifying drugs among patients with multiple sclerosis in germany: a retrospective cohort study. PLoS One. 2015;10:e0133279.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–97.

    Article  CAS  PubMed  Google Scholar 

  27. Devonshire V, Lapierre Y, Macdonell R, et al. The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis. Eur J Neurol. 2011;18:69–77.

    Article  CAS  PubMed  Google Scholar 

  28. Locklear J, Phillips A, Munsell M, Frean M, Menzin J. An assessment of adherence among multiple sclerosis patients newly initiating treatment with a self-injectable versus oral disease-modifying drug. Neurology. 2015;84(P3):281.

    Google Scholar 

  29. Locklear J, Phillips A, Kozma C. An exploratory analysis of predictors of disease-modifying drug adherence using data from a panel survey of patients with multiple sclerosis. Neurology. 2015;84(P3):217.

    Google Scholar 

  30. Burke LE, Sereika SM, Music E, Warziski M, Styn MA, Stone A. Using instrumented paper diaries to document self-monitoring patterns in weight loss. Contemp Clin Trials. 2008;29:182–93.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lugaresi A, Florio C, Brescia-Morra V, et al. Patient adherence to and tolerability of self-administered interferon ß-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study. BMC Neurol. 2012;12:7.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Weller I, Saake A, Schreiner T, Vogelreuter J, Petroff N. Patient satisfaction with the BETACONNECT™ autoinjector for interferon beta-1b. Patient Prefer Adherence. 2015;9:951–9.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The BETAPATH study was funded by Bayer Vital GmbH (Leverkusen, Germany). The sponsor had a role in the design and conduct of the study, analysis of the data, and preparation of the manuscript. The article processing charges for this publication were funded by Bayer Vital GmbH. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Medical writing services from Dr. Carmen Koch, employee of KW medipoint, were funded by Bayer Vital GmbH.

Disclosures

Uwe Klaus Zettl received speaking fees and financial support for research activities from Almirall, Bayer HealthCare, Biogen, Merck Serono, Novartis, Sanofi, and Teva. Ulrike Bauer-Steinhusen, Thomas Glaser, and Jörg Czekalla are employees of Bayer Vital GmbH and Bayer Pharma AG, respectively. Klaus Hechenbichler declares no potential conflicts of interest in connection with this paper. Volker Limmroth received speaking fees and financial support for research activities from Bayer HealthCare, Biogen, Genzyme, Novartis, Roche, Sanofi, and Teva. Michael Hecker received speaking fees and travel support from Bayer HealthCare, Biogen, Novartis, and Teva.

Compliance with Ethics Guidelines

The study was conducted in accordance with ethical principles outlined in the International Committee on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and in the Declaration of Helsinki. The study was approved by the Ethics Committee of the Ärztekammer Nordrhein and registered at ClinicalTrials.gov with the identifier NCT00902135. Written informed consent was obtained from each patient before enrollment into the study.

Author information

Authors and Affiliations

  1. Department of Neurology, Neuroimmunology Section, University of Rostock, Rostock, Germany

    Uwe Klaus Zettl & Michael Hecker

  2. Neurology, Immunology, and Ophthalmology, Bayer Vital GmbH, Leverkusen, Germany

    Ulrike Bauer-Steinhusen & Thomas Glaser

  3. Global Medical Department - Real World Data Outcomes, Bayer Pharma AG, Berlin, Germany

    Jörg Czekalla

  4. Institute Dr. Schauerte, Munich, Germany

    Klaus Hechenbichler

  5. Clinic for Neurology and Palliative Medicine, Municipal Hospital Köln-Merheim, Cologne, Germany

    Volker Limmroth

Authors
  1. Uwe Klaus Zettl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ulrike Bauer-Steinhusen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Glaser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jörg Czekalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Klaus Hechenbichler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Volker Limmroth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael Hecker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Hecker.

Additional information

For the Study Group.

Enhanced content

To view enhanced content for this article go to www.medengine.com/Redeem/0D84F060099D9DFB.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 261 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zettl, U.K., Bauer-Steinhusen, U., Glaser, T. et al. Adherence to Long-Term Interferon Beta-1b Injection Therapy in Patients with Multiple Sclerosis Using an Electronic Diary. Adv Ther 33, 834–847 (2016). https://doi.org/10.1007/s12325-016-0325-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-016-0325-6

Keywords

Search

Navigation