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. 2017 Apr 19:13:1115-1124.
doi: 10.2147/NDT.S133145. eCollection 2017.

Long-term effect of galantamine on cognitive function in patients with Alzheimer's disease versus a simulated disease trajectory: an observational study in the clinical setting

Ryoko Nakagawa  1 , Takashi Ohnishi  1 , Hisanori Kobayashi  1 , Toshio Yamaoka  2 , Tsutomu Yajima  3 , Ai Tanimura  4 , Toshiya Kato  4 , Kazutake Yoshizawa  1
Affiliations

Long-term effect of galantamine on cognitive function in patients with Alzheimer's disease versus a simulated disease trajectory: an observational study in the clinical setting

Ryoko Nakagawa et al. Neuropsychiatr Dis Treat. .

Abstract

Background: Long-term maintenance of cognitive function is an important goal of treatment for Alzheimer's disease (AD), but evidence about the long-term efficacy of cholinesterase inhibitors is sparse. To evaluate the long-term efficacy and safety of galantamine for AD in routine clinical practice, we conducted a 72-week post-marketing surveillance study. The effect of galantamine on cognitive function was estimated in comparison with a simulated disease trajectory.

Patients and methods: Patients with mild-to-moderate AD received flexible dosing of galantamine (16-24 mg/day) during this study. Cognitive function was assessed by the mini mental state examination (MMSE) and the clinical status was determined by the Clinical Global Impression-Improvement (CGI-I). Changes of the MMSE score without treatment were estimated in each patient using Mendiondo's model. Generalized linear mixed model analysis was performed to compare the simulated MMSE scores with the actual scores.

Results: Of the 661 patients who were enrolled, 642 were evaluable for safety and 554 were assessed for efficacy. The discontinuation rate was 46.73%. Cognitive decline indicated by the mean change of actual MMSE scores was significantly smaller than the simulated decline. Individual analysis demonstrated that >70% of patients had better actual MMSE scores than their simulated scores. Significant improvement of CGI-I was also observed during the observation period. Adverse events occurred in 28.5% of patients and were serious in 8.41%. The reported events generally corresponded with the safety profile of galantamine in previous studies.

Conclusion: These findings support the long-term efficacy of galantamine for maintaining cognitive function and the clinical state in AD patients. Treatment with galantamine was generally safe. Importantly, this study revealed that galantamine improved cognitive function above the predicted level in >70% of the patients.

Keywords: Alzheimer’s disease; cholinesterase inhibitor; cognitive function; disease progression; real-world evidence.

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Conflict of interest statement

Disclosure All authors are full-time employees of Janssen Pharmaceutical K.K., a division of Johnson & Johnson, Japan. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flow chart of subject disposition. Abbreviation: TEAEs, treatment emergent adverse events.
Figure 2
Figure 2
Kaplan–Meier curves for discontinuation during the observation period.
Figure 3
Figure 3
Mean actual changes of MMSE scores and simulated changes during the observation period. Notes: Bars represent the standard error. GLMM analysis with post-hoc testing: a) differences between actual OC and predicted scores, b) differences between actual, LOEF, and predicted scores. Asterisks denote significant differences: *P<0.05, **P<0.01, ***P<0.001. Abbreviations: GLMM, generalized linear mixed model; LOEF, last observation estimated forward; MMSE, mini mental state examination; OC, observed case.
Figure 4
Figure 4
Clinical Global Impression-Improvement score over time during the observation period.
See this image and copyright information in PMC

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