Advertisement

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

  • Chiung-Chih Chang
  • Giia-Sheun Peng
  • Te-Jen Lai
  • Chien-Hsun Li
  • Ching-Kuan LiuEmail author
Original Research

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.

Keywords

Alzheimer’s disease Cognition Dementia Neurology Rivastigmine Treatment persistence 

Notes

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.

References

  1. 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. 2.
    Yang Y-H. Alzheimer’s disease in Taiwan: registration and prevalence. Neurodegen Dis Manag. 2013;3:195–7.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 7.
    Fuh J-L, Wang S-J. Dementia in Taiwan: past, present, and future. Acta Neurol Taiwan. 2008;17:153–61.Google Scholar
  8. 8.
    Weinstock M. Selectivity of cholinesterase inhibition: clinical implications for the treatment of Alzheimer’s disease. CNS Drugs. 1999;12:307–23.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 11.
    Ginsberg MD. Carbon monoxide intoxication: clinical features, neuropathology and mechanisms of injury. J Toxicol Clin Toxicol. 1985;23:281–8.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 15.
    Birks JS, Chong LY, Grimley Evans J. Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2015;9:CD001191.Google Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.Google Scholar
  22. 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.CrossRefGoogle Scholar

Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2019

Authors and Affiliations

  • Chiung-Chih Chang
    • 1
  • Giia-Sheun Peng
    • 2
  • Te-Jen Lai
    • 3
  • Chien-Hsun Li
    • 4
  • Ching-Kuan Liu
    • 4
    • 5
    • 6
    Email author
  1. 1.Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKao-hsiungTaiwan
  2. 2.Taipei Veterans General Hospital Hsinchu BranchHsinchu CountyTaiwan
  3. 3.Institute of Medicine and Department of PsychiatryChung Shan Medical University HospitalTaichungTaiwan
  4. 4.Department of NeurologyKaohsiung Medical University HospitalKaohsiungTaiwan
  5. 5.Department of NeurologySchool of Medicine, Kaohsiung Medical UniversityKaohsiungTaiwan
  6. 6.Graduate Institute of MedicineCollege of Medicine, Kaohsiung Medical UniversityKaohsiungTaiwan

Personalised recommendations