Effects of rivastigmine on common symptomatology of Alzheimer’s disease (EXPLORE)

Abstract

Objective:

To evaluate, in a real-world clinical setting, the efficacy of rivastigmine in the management of six symptoms commonly associated with Alzheimer's disease (AD).

Methods:

This was a naturalistic, prospective, open-label, multi-centre, post-marketing, observational study. Data were collected by the participating study physicians at their practices across Canada. Subjects had a clinical diagnosis of mild-to-moderate AD and were prescribed rivastigmine by their treating physician. Efficacy was primarily evaluated by a physician-assessed, abbreviated Clinical Global Impression of Change (CGI-C) scale, focusing on six symptoms: attention, apathy, anxiety, agitation, irritability and sleep disturbance. Changes were assessed at months 3, 6 and 12. Several other patient-, physician- and caregiver-related assessments were also included.

Results:

A total of 4460 patients were recruited by 353 study physicians; 3800 were deemed evaluable, having taken at least one dose of rivastigmine and with at least one post-baseline assessment. At baseline, attention problems were present in 86.0% of evaluable patients, anxiety in 77.3%, apathy in 68.3%, irritability in 64.0%, agitation in 54.6% and sleep disturbance in 54.5%. At both month 6 and month 12, for each symptom, the percentage of patients experiencing an improvement was considerably larger than the percentage of patients who experienced symptom worsening. Among evaluable patients, the proportions improving vs. deteriorating at month 6 were 46.4 vs. 8.8% for attention; 42.8 vs. 7.2% for apathy; 41.1 vs. 9.4% for anxiety; 33.8 vs. 7.7% for agitation; 35.1 vs. 10.1% for irritability; and 30.8 vs. 5.4% for sleep disturbance.

Limitations:

Open-label studies have an inherent potential for bias by both the caregiver and the physician.

Conclusions:

This study demonstrates that a considerable proportion of rivastigmine-treated patients experience improvements on each of the six symptoms studied. These findings add further support to previous randomised, clinical studies showing benefit of rivastigmine in AD.

Key words::

• Alzheimer's disease
• Agitation
• Anxiety
• Apathy
• Attention
• Irritability
• Rivastigmine
• Sleep disturbance

Transparency

Declaration of funding

Funding for this study was provided by Novartis Pharmaceuticals Canada, Inc.

Declaration of financial/other relationships

W.D. has disclosed that he has received honoraria for speaking engagements, participation on advisory boards and design of educational programs for Novartis and other pharmaceutical companies with products in the field of dementia management. No honorarium was received for development of this manuscript. A.J. has disclosed that she has received honoraria for educational programs and participation on advisory boards for Novartis and other pharmaceutical companies with products in the field of dementia management. Also, she has served as principal investigator in drug-company sponsored, randomised controlled clinical trials for Novartis and other pharmaceutical companies with products in the field of dementia management. No honorarium was received for development of this manuscript. S.G. has disclosed that he has received honoraria for participation in scientific advisory boards and for consultant work for Novartis and other pharmaceutical companies with products in the field of dementia management. Also he has served as investigator in clinical trials sponsored by Novartis and other pharmaceutical companies with products in the field of dementia management. No honorarium was received for development of this manuscript. R.S. has disclosed that she is an employee of Novartis Pharmaceuticals Canada, Inc. B.R. has disclosed that she is an employee of an independent statistical consulting company, under contract to Novartis Pharmaceuticals Canada Inc.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgement

The authors thank the individual study physicians for their participation in the study. Statistical analysis services were provided by Everest Clinical Research Services Inc. and editorial assistance for the manuscript was provided by Pharm Team Communications.

The study protocol was developed by the sponsor in collaboration with the Steering Committee.

Interim results of this study were presented as a poster (Dalziel W, Juby A, Keren R, Gauthier S, Schecter R. EXPLORE: Improvements in 6 symptoms of early AD following 6 months of treatment with rivastigmine) at The Canadian Association of Gerontology’s 35th Annual Scientific and Educational Meeting, Québec, Quebéc, October 26–28, 2006.

Notes

*Exelon is a registered trademark manufactured by Novartis AG, Basel, Switzerland.