Skip to main content
SpringerLink
Log in

A 48-Week, Multicenter, Open-Label, Observational Study Evaluating Oral Rivastigmine in Patients with Mild-to-Moderate Alzheimer’s Disease in Taiwan

Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer’s type. This study assessed the short- and long-term effectiveness and safety of rivastigmine in patients with mild-to-moderate Alzheimer’s disease (AD) in a real-world clinical setting in Taiwan.

Methods

This was a 48-week, single-arm, open-label, prospective, observational, post-marketing surveillance, multicenter study. The primary outcomes were change from baseline to week 48 in the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scores. One-year persistence to treatment, effect on activities of daily living, and incidence of adverse events (AEs) were also assessed.

Results

Overall, 151 patients were enrolled in the study, of which 91 (60.26%) completed this study. At the end of the study, the mean rivastigmine dose received by the patients was 6.59 mg/day. At week 48, the changes in mean [standard deviation (SD)] MMSE and CDR scores in the intent-to-treat (ITT) population from baseline were − 1.00 (3.8; p = 0.0344) and 0.07 (0.29; p = 0.0403), respectively. The most frequently reported AEs by preferred term were dizziness (12.58%) and nausea (9.27%). No new or unexpected AEs were observed, and 30 (20.13%) patients in the ITT population were on rivastigmine therapy for 1 year without treatment discontinuation.

Conclusion

Despite the low 1-year persistence rate, rivastigmine showed a stabilizing effect on declining cognition in patients with mild-to-moderate AD in a real-world scenario. Rivastigmine is well tolerated at 6.0–9.0 mg/day with no unexpected safety concerns.

Funding

Novartis Co. Ltd., Taipei, Taiwan.

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

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and meta-analysis. Alzheimers Dement. 2013;9(63–75):e2.

    Google Scholar 

  2. Yang Y-H. Alzheimer’s disease in Taiwan: registration and prevalence. Neurodegen Dis Manag. 2013;3:195–7.

    Article  Google Scholar 

  3. Lapresle J, Fardeau M. The central nervous system and carbon monoxide poisoning. II. Anatomical study of brain lesions following intoxication with carbon monoxide (22 cases). Prog Brain Res. 1967;24:31–74.

    Article  CAS  PubMed  Google Scholar 

  4. Wang W-F, Chiu P-Y, Lin Y-T, Hu C-J, Fuh J-L, Yang Y-H. Registration of Alzheimer’s disease in Taiwan: patient and informant. Am J Alzheimers Dis Other Demen. 2014;29:18–22.

    Article  PubMed  Google Scholar 

  5. Sun Y, Lee HJ, Yang SC, Chen TF, Lin KN, Lin CC, et al. A nationwide survey of mild cognitive impairment and dementia, including very mild dementia, in Taiwan. PLoS Oone. 2014;9:e100303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wu YT, Lee HY, Norton S, Chen C, Chen H, He C, et al. Prevalence studies of dementia in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis. PLoS One. 2013;8:e66252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fuh J-L, Wang S-J. Dementia in Taiwan: past, present, and future. Acta Neurol Taiwan. 2008;17:153–61.

    PubMed  Google Scholar 

  8. Weinstock M. Selectivity of cholinesterase inhibition: clinical implications for the treatment of Alzheimer’s disease. CNS Drugs. 1999;12:307–23.

    Article  CAS  Google Scholar 

  9. Chang CC, Lee YC, Chang WN, Chen SS, Lui CC, Chang HW, et al. Damage of white matter tract correlated with neuropsychological deficits in carbon monoxide intoxication after hyperbaric oxygen therapy. J Neurotrauma. 2009;26:1263–70.

    Article  PubMed  Google Scholar 

  10. Chiu P-Y, Dai D-E, Hsu H-P, Lee C, Lin J-J, Kuo H-C, et al. Safety/tolerability and efficacy of rivastigmine in Taiwanese patients with Alzheimer’s Disease: a prospective post-marketing surveillance Study. Clin Drug Investig. 2009;29:729–38.

    Article  CAS  PubMed  Google Scholar 

  11. Ginsberg MD. Carbon monoxide intoxication: clinical features, neuropathology and mechanisms of injury. J Toxicol Clin Toxicol. 1985;23:281–8.

    Article  CAS  PubMed  Google Scholar 

  12. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984;34:939–44.

    Article  CAS  PubMed  Google Scholar 

  13. Doody RS, Pavlik V, Massman P, Rountree S, Darby S, Chan W. Predicting progression of Alzheimer’s disease. Alzheimers Res Ther. 2010;2:2.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Winblad B, Cummings J, Andreasen N, Grossberg G, Onofrj M, Sadowsky C, et al. A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer's disease—rivastigmine patch versus capsule. Int J Geriatr Psychiatry. 2007;22:456–67.

    Article  PubMed  Google Scholar 

  15. Birks JS, Chong LY, Grimley Evans J. Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2015;9:CD001191.

    PubMed  Google Scholar 

  16. Karaman Y, Erdoğan F, Köseoğlu E, Turan T, Ersoy AO. A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease. Dement Geriatr Cogn Disord. 2005;19:51–6.

    Article  CAS  PubMed  Google Scholar 

  17. Burke WJ, Houston MJ, Boust SJ, Roccaforte WH. Use of the geriatric depression scale in dementia of the Alzheimer type. J Am Geriatr Soc. 1989;37:856–60.

    Article  CAS  PubMed  Google Scholar 

  18. Andersen CK, Wittrup-Jensen KU, Lolk A, Andersen K, Kragh-Sørensen P. Ability to perform activities of daily living is the main factor affecting quality of life in patients with dementia. Health Qual Life Outcomes. 2004;2:52.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Brewer L, Bennett K, McGreevy C, Williams D. A population-based study of dosing and persistence with anti-dementia medications. Eur J Clin Pharmacol. 2013;69:1467–75.

    Article  PubMed  Google Scholar 

  20. Sun Y, Lai MS, Lu CJ, Chen RC. How long can patients with mild or moderate Alzheimer's dementia maintain both the cognition and the therapy of cholinesterase inhibitors: a national population-based study. Eur J Neurol. 2008;15:278–83.

    Article  CAS  PubMed  Google Scholar 

  21. Lai TH, Wang WF, Yip BS, Yang YW, Peng GS, Tsai SJ, et al. Real-world evaluation of compliance and preference in Alzheimer's disease treatment: an observational study in Taiwan. Patient Prefer Adherence. 2016;10:383–90.

    PubMed  PubMed Central  Google Scholar 

  22. Gardette V, Lapeyre-Mestre M, Piau A, Gallini A, Cantet C, Montastruc JL, et al. A 2-year prospective cohort study of antidementia drug non-persistency in mild-to-moderate Alzheimer's disease in Europe: predictors of discontinuation and switch in the ICTUS study. CNS Drugs. 2014;28:157–70.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the participants of the study.

Funding

This study was funded by Novartis Co. Ltd., Taipei, Taiwan. The article processing fee was funded by Novartis Co. Ltd., Taipei, Taiwan. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Medical Writing Assistance

The authors thank Dinesh T. Makhija, Novartis Healthcare Pvt. Ltd, Hyderabad, India, for providing medical writing assistance.

Authorship

All 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 for the version to be published.

Disclosures

Chiung-Chih Chang, Giia-Sheun Peng, Te-Jen Lai, Chien-Hsun Li, and Ching-Kuan Liu have nothing to disclose.

Compliance with Ethics Guidelines

The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the following institutional review boards: the institutional review board of Tri-Service General Hospital, Chang Gung Medical Foundation Institutional Review Board, the Institutional Review Board of the Kaohsiung Medical University Hospital, and the Institutional Review Board of Chung Shan Medical University Hospital. All patients provided written informed consent before enrollment.

Data Availability

The data sets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Authors and Affiliations

  1. Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kao-hsiung, Taiwan

    Chiung-Chih Chang

  2. Taipei Veterans General Hospital Hsinchu Branch, Hsinchu County, Taiwan

    Giia-Sheun Peng

  3. Institute of Medicine and Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan

    Te-Jen Lai

  4. Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Chien-Hsun Li & Ching-Kuan Liu

  5. Department of Neurology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ching-Kuan Liu

  6. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ching-Kuan Liu

Authors
  1. Chiung-Chih Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giia-Sheun Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Te-Jen Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chien-Hsun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ching-Kuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ching-Kuan Liu.

Additional information

Enhanced Digital Features

To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare.7868804

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chang, CC., Peng, GS., Lai, TJ. et al. A 48-Week, Multicenter, Open-Label, Observational Study Evaluating Oral Rivastigmine in Patients with Mild-to-Moderate Alzheimer’s Disease in Taiwan. Adv Ther 36, 1455–1464 (2019). https://doi.org/10.1007/s12325-019-00939-0

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-019-00939-0

Keywords

search

Navigation