Download `real-world` study

Real-World Evaluation of Compliance and
Preference in Alzheimer’s Disease Treatment:
the RECAP Study
楊玉婉 醫師
中國醫藥大學附設醫院
TW1408235288
Contents
• Background
• Real-World Evaluation of Compliance and Preference in Alzheimer’s
Disease Treatment (RECAP) study
• Summary
2
Epidemiology of Alzheimer’s disease
Asia
15.94 million
East Asia
5.49 million
North Africa & Middle East
1.15 million
South East Asia
2.48 million
2010 Total worldwide prevalence: 35.6 million
1.15 million
North Africa & Middle East
2.48 million
South East Asia
East Asia
5.49 million
Asia
15.94 million
0
4
8
12
Adapted from Prince M, et al. Alzheimers Dement 2013;9:63–75.
16
3
Distribution of cognitive facilities in the normal intact
human brain
Language
Visuoperception
Declarative
memory
Complex
activities
Hans Förstl for Neuronet, Novartis
4
What these symptoms mean to a person with
Alzheimer’s disease
• Forgetting more and more things … and people
• Loss of initiative and decreased judgment
• Disorientation to time and place
• Difficulty in finding the right words or understanding what people are saying
• Difficulty in performing previously routine everyday tasks
• Personality and mood changes
• Isolation, depression
• Loss of independence
ADI website. www.alz.co.uk/alzheimers/symptoms.html. Accessed 27 March 2014.
5
Alzheimer’s disease has a high impact on society
• Prevalence of dementia increases
markedly from the age of 651
• AD is the leading cause of disability3
• AD greatly impairs patients’ cognition,
behavior, and functioning4
• AD greatly affects caregivers (stress, loss
of work)
– In the United Kingdom, £123 million per
year in taxes are lost because caregivers
have to stop or cut back working5
Estimates for prevalence of dementia*1
Age, years
Prevalence, Asia, %
60-64
1.8
65-69
2.8
70-74
4.5
75-79
7.5
80-84
12.5
85-89
20.3
≥90
38.3
Leading causes of YLD in high-income countries in
2001 (WHO)3
Cause
YLD (millions of years)
AD and other dementias
6.33
Osteoarthritis
3.77
CVD
3.46
COPD
2.86
Diabetes mellitus
2.25
1. Prince M, et al. Alzheimers Dement 2013;9:63–75.
2. van der Flier WM, et al. J Neurol Neurosurg Psychiatry 2005;76:v2–v7.
*AD is chiefly identified as the frequent cause of dementia.2
3. Disease Control Priority Project, www.dcp2.org/pubs/GBD/3/Table/3.12
AD: Alzheimer’s disease; COPD, chronic obstructive pulmonary
4. Alzheimer's Association. 2005.
disease; CVD, cerebrovascular disease; WHO, World Health
5. Knapp M, et al. www.alzheimers.org.uk/News_and_campaigns/Forthcoming_events on
Organization; YLD, year life with disability.
9/4/2007.
6
Improved compliance to ChEI therapy could result in
lower overall costs of care
– Average time to oral ChEI
discontinuation in 17,742 US patients:
120–135 days1
– Cognitive and memory impairment
hamper compliance in AD
1.0
Probability of
continuous drug use
• Persistence with older oral ChEI
therapies declines rapidly
Donepezil
Rivastigmine
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
100
200
300
400
Persistency days
Improved treatment compliance is
associated with net savings in health
care cost during the first year from
starting therapy2
Net 1-yr healthcare cost savings with 10% greater
adherence to therapy
$215
200
Cost measure (US $)
•
Pharmacy
cost
-$783
-$568
Medical
Cost
Net
savings
0
-200
-400
-600
-800
1. Singh G, et al. J Am Geriatr Soc 2005;53:1269–1270.
2. Harada AS, et al. ISPOR annual meeting; May 20–24, 2006; PA, USA.
AD, Alzheimer’s disease; ChEI,
cholinesterase inhibitor.
7
Challenges with ChEI therapy
•
Underdosing and poor treatment compliance are key issues1
•
The answer is to improve therapeutic benefit by1-4:
–
–
–
–
•
1.
2.
3.
4.
5.
Optimizing dosing
Monitoring treatment compliance
Simplifying administration
Minimizing side effects with smooth
drug delivery
Not a cure5
Emre M, et al. CNS Neurosci Ther 2010;16:246–253.
Priano L, et al. Drugs Aging 2006;23:357–375.
Mercier F, et al. Curr Med Res Opin 2007;23:3199–3204.
Lefèvre G, et al. Clin Pharm Ther 2008;1:106–114.
Overshott R. J Neurol Neurosurg Psychiatry 2005;76:v53–v59.
ChEI, cholinesterase inhibitor.
8
First-line treatment approaches with ChEIs
Treatment approach1
Common brand name
Approved indications
Rivastigmine
Exelon®
Exelon® Patch
AD and PDD*
Capsules
Available formulations
Oral solution
Transdermal patch
Dosing schedule
Capsules and liquid –
b.i.d.
Donepezil
Aricept®
AD
Capsules
ODT
q.d.
Galantamine
Razadyne®
Reminyl®
AD
Capsules
q.d.
Patch – q.d.
*The rivastigmine patch is the first and only transdermal approach to dementia treatment, having been approved for mild-to-moderate
Alzheimer’s disease in more than 90 countries, including more than 20 countries, where it is also approved for Parkinson’s disease
dementia. Rivastigmine patch is also approved for the treatment of patients with severe Alzheimer’s disease in the United States, Argentina,
Chile, Israel and South Korea.2
AD, Alzheimer’s disease; ChEI, cholinesterase inhibitor; ODT,
1. Hort J, et al. Eur J Neurol 2010;17:1236–1248.
orally-disintegrating tablets; PDD, Parkinson’s disease dementia.
2. Novartis Financial Report 2013. http://www.novartis.com/downloads/investors/financial-results/quarterly-results/2014-01-interim-financialreport.pdf. Accessed on April 21, 2014.
9
Rationale for a transdermal patch in Alzheimer’s disease
• Providing continuous drug delivery over 24 hours for longer duration of action
• Allowing easier and faster access to higher doses
• Reducing side effects by providing smooth drug delivery
• Simplifying treatment for elderly patients often taking many other medicines
• Making administration independent of food intake
• Avoiding the first-pass effect
• Helping family members to monitor treatment compliance
• Providing visual reassurance of treatment
Priano L, et al. Drugs Aging 2006;23:357–375.
10
Schematic representation of PK profiles for oral (b.i.d.,
t.i.d.) and patch drug delivery
• Smoother pharmacokinetic profile expected to provide better tolerability
• Better tolerability may allow access to high-dose efficacy
Predicted relative
plasma concentrations
• Convenience of once-daily dosing
b.i.d. capsule
Transdermal patch
t.i.d. capsule
10
30
50
Time post first dose (h)
Lefèvre G, et al. Clin Pharm Ther 2008;1:106–114.
70
90
b.i.d., twice daily; t.i.d., thrice daily;
PK, pharmacokinetics.
11
Rivastigmine transdermal patch: smooth continuous
delivery through the skin
• Rivastigmine 9.5 mg/24 h patch delivered comparable average concentrations
(AUC) to those provided by an oral dose of 6 mg b.i.d. (12 mg/day)*
Rivastigmine concentration (ng/mL)
25
Capsule 6 mg b.i.d.
Patch 9.5 mg/24 hour
20
15
10
5
0
0
6
12
Time (hours)
18
24
* Model-predicted analysis based on actual patient data corrected for body weight
Mercier F, et al. Curr Med Res Opin 2007;23:3199–3204.
b.i.d., twice daily.
12
Summary of caregiver feedback obtained from IDEAL
study
• Over 70% of caregivers preferred the transdermal patch to the capsule overall
• Caregivers preferred the transdermal patch to the capsule for following the
schedule and ease of use
• Caregivers preferred the transdermal patch irrespective of the size
• Caregivers indicated that the transdermal patch interfered less with daily life
Winblad B, et al. Int J Geriatr Psychiatry 2007;22:456–467.
13
Contents
• Background
• Real-World Evaluation of Compliance and Preference in Alzheimer’s
Disease Treatment (RECAP) study
• Summary
14
Rationale for the RECAP Study
•
IDEAL sub-study showed higher caregiver treatment preference (72%) for the transdermal
than oral treatment1
•
EMBRACE study demonstrated that the caregivers of 88.2% of patients with mild-tomoderate AD preferred transdermal patch over oral medications2
•
Limited literature, mostly from Western countries, is available on the caregiver treatment
preference and patient compliance with the transdermal rivastigmine patch in a real-world
clinical setting2-5
•
No such data are available from Asia and Middle East, which account for a sizeable
proportion of patients with AD6
•
RECAP study was designed to evaluate caregiver treatment preference and compliance in
patients with AD treated with oral or transdermal monotherapy in a real-world clinical setting
and an ethnically diverse population from Asia and the Middle East7
1. Winblad B, et al. Int J Geriatr Psychiatry 2007;22:485–491.
2. Gauthier S, et al. Curr Med Res Opin 2013;29:989–1000.
3. Cruz Jentoft AJ, et al. Neurologia 2014;29:1–10.
4. Boada M, et al. Dement Geriatr Cogn Disord 2013;35:23–33.
5. Bernabei R, et al. Dement Geriatr Cogn Dis Extra 2012;2:418–432.
6. Prince M, et al. Alzheimers Dement 2013;9:63–75.
7. Kandiah N. Poster presented at: 26th AAIC; July 12–17, 2014;
Copenhagen,Denmark.
AD, Alzheimer’s disease; EMBRACE, Effective Management of
Alzheimer’s disease By TReating pAtients and relieving Caregivers
with Exelon Patch; IDEAL, Investigation of transDermal Exelon in
ALzheimer’s disease; RECAP, Real-World Evaluation of
Compliance and Preference in Alzheimer’s Disease Treatment.
15
Study objectives
Primary objective
•
Assess caregiver treatment preference and compliance in AD patients treated with either
oral or transdermal monotherapy
Secondary objectives
•
Evaluate the final dosage reached
•
Evaluate the number of psychotropic drugs used per patient in both groups (oral and
transdermal monotherapy) and the percentage of patients who need at least 1 psychotropic
drug
•
Assess physicians preference for oral or transdermal monotherapy
•
Optional*: Assess the change in total score within any of these scales (MMSE, Caregiver
Behavioral Scale, CGI-C, ADCS-ADL, CDR scale, GDS)
Observe the frequency of adverse events and discontinuations of treatment
•
*Optional objectives are to be retained if part of routine clinical practice in the relevant country.
MMSE, Mini-Mental State Examination; CGI-C, Clinical Global Impression of Change; ADCS-ADL, Alzheimer's Disease
Cooperative Study Activities of Daily Living; CDR, Clinical Dementia Rating; GDS, Global Deterioration Scale.
Novartis, data on file.
16
Study design: 24-week, prospective, multinational,
non-interventional, ‘real-world’ study
• RECAP was a 24-week, prospective, multinational, non-interventional study
• Patients with mild-to-moderate Alzheimer’s disease were grouped into two
treatment cohorts: oral (cholinesterase inhibitors or memantine) and transdermal
(rivastigmine)
ChEI or memantine oral monotherapy
Rivastigmine transdermal monotherapy
Visit 1
Baseline
Study entry
Optional Visit 2
12 weeks
Visit 3
24 weeks
End of the study
Observational period of 24 weeks ± 8 weeks
ChEI, cholinesterase inhibitor.
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
17
Study endpoints
Primary
•
Caregiver preference and caregiver’s assessment of patient compliance as evaluated by
the Caregiver Medication Questionnaire (CMQ) at the end of study
Secondary
•
Assessment of drug regimen among patients on cholinesterase inhibitors and memantine
at the end of study (total daily dosage reached)
•
Use of concomitant psychotropic medication and number of psychotropic medications
used (1, 2, 3 or >3) per patient at the end of study
•
Physician’s preference for oral or transdermal patch medication (including top three
reasons for their preference) at the end of study
•
Secondary efficacy analyses included assessments of MMSE, Caregiver Behavioral
Scale, CGI-C, ADCS-ADL, CDR scale, GDS
•
Adverse events and discontinuation of the medication
MMSE, Mini-Mental State Examination; CGI-C, Clinical Global Impression of Change; ADCS-ADL, Alzheimer's Disease
Cooperative Study Activities of Daily Living; CDR, Clinical Dementia Rating; GDS, Global Deterioration Scale.
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
18
Inclusion and exclusion criteria
Inclusion criteria
•
•
•
•
Male and female outpatients, at least 50 years of age, diagnosed with mild-to-moderate
AD
Patients who have been prescribed oral or transdermal monotherapy (ChEI or
memantine) in adherence with the PI/SmPC
Patients with a caregiver willing and able to answer the Caregiver Medication
Questionnaire
Patients who consented to have their data collected
Exclusion criteria
•
Contraindications mentioned in the local PI/SmPC
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
AD, Alzheimer's disease; ChEI, cholinesterase inhibitor;
PI, Prescribing Information; SmPC, Summary of Product
Characteristics.
19
Data analyzed from 1931 patients with Alzheimer's
disease pooled from 6 participating countries
South Korea
N = 398
Lebanon
N = 100
Taiwan
N = 301
Singapore
Egypt
N = 503
India
N = 56
N = 573
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
20
Patient disposition
Enrolled in the study
N=1931
Oral monotherapy cohort
n=953
Patients completed the study
n=822
Analysis populations
• Full analysis set: 953 (100%)
• Effectiveness set: 854 (89.6%)
Patients discontinued prematurely
from the study
n=128
Transdermal monotherapy cohort
n=978
Patients completed the study
n=813
Analysis populations
• Full analysis set: 978 (100%)
• Effectiveness set: 865 (88.4%)
Patients discontinued prematurely
from the study
n=161
Full Analysis Set (FAS) consists of all patients who provided informed consent and received at least one dose of medication under observation.
Effectiveness set excluded patients without any post-baseline effectiveness assessment. In addition, for any patient who switched treatment
cohort during the study, effectiveness data collected after the time of switch were excluded.
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
21
Demographics and baseline characteristics
Oral monotherapy
cohort
n=953
Transdermal monotherapy
cohort
n=978
Total
N=1931
Age, years a
Gender, n (%)
Male
Female
Race, n (%) b
Caucasian
Asian
Other
Duration of AD, years
Prior treatment for AD, n (%) c
72.6 (8.45)
72.9 (8.24)
72.8 (8.34)
470 (49.3)
483 (50.7)
485 (49.6)
493 (50.4)
955 (49.5)
976 (50.5)
262 (27.5)
656 (68.8)
34 (3.6)
0.9 (1.53)
260 (26.6)
671 (68.6)
47 (4.8)
0.8 (1.30)
522 (27.0)
1327 (68.7)
81 (4.2)
0.9 (1.42)
Drug therapy
No drug therapy
Any family history of AD d
Yes
No
Current living situation, n (%) e
Living alone
Living with caregiver or other
individual
Assisted living/group home
MMSE score f
209 (21.9)
744 (78.1)
309 (31.6)
668 (68.3)
518 (26.8)
1412 (73.1)
132 (13.9)
820 (86.0)
115 (11.8)
862 (88.1)
247 (12.8)
1682 (87.1)
49 (5.1)
879 (92.2)
51 (5.2)
892 (91.2)
100 (5.2)
1771 (91.7)
24 (2.5)
34 (3.5)
58 (3.0)
17.8 (4.70)
17.7 (4.67)
17.8 (4.68)
Data are shown as mean (SD), unless otherwise stated; a Information about age was missing for one patient in the oral monotherapy cohort;
b Information about race was missing for one patient in the oral monotherapy cohort; c Information about prior treatment for AD was missing for one
patient in transdermal monotherapy cohort; d Family history of AD was missing for two patients (one in each cohort); e Information about current
living situation was missing for two patient (one in each cohort); f Information about MMSE score is available only from proportion of patients.
AD, Alzheimer’s disease; MMSE, Mini-Mental State
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
Examination, SD, standard deviation.
22
Caregivers preferred transdermal when patients exposed
to both form of therapies, at Week 24
• When patients were exposed to oral or transdermal therapy only, the caregiver
preference at Week 24 was in favor of the treatment the patient was exposed to
*
100
93.8
*
Caregiver preference (%)
90
*
82.7
n=510
80
n=253
70
64.9
60
n=510
50
40
35.1
30
n=276
17.3
20
n=53
6.3
10
n=34
0
Prior exposure to
oral medication only
(N=814)†
Preference for oral monotherapy
†
Prior exposure to
transdermal medication only
34
(N=575)†
Prior exposure to oral and
transdermal medications
(N=330)†
Preference for transdermal monotherapy
*p<0.0001
Patients in the effectiveness set with missing caregiver preference assessment were not included in the calculations
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
23
Patient compliance was higher for transdermal therapy,
at Week 24
• At Week 24, numerically greater proportion of patients on transdermal patch in
‘always took the medication as prescribed’ category (28.6% versus 24.9%,
respectively)
10
*
8.71
9
7.72
Mean score
8
n=805
n=807
7
6
5
4
3
2
1
0
Oral monotherapy
Transdermal monotherapy
*p<0.0001
Rated on an 11-point scale from 0=Never took the medication as prescribed up to a maximum of 10=Always took
the medication as prescribed by the Caregiver Medication Questionnaire.
Caregiver assessment of patience compliance was done at end of the study. End of the study was at Visit 3 (Week 24)
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
24
Total daily dosage reached
• Higher percentage of patients reached the higher dose with rivastigmine
transdermal patch compared with other oral acetyl cholinesterase inhibitors
(AChEIs) used as monotherapy
67.9
70
60.6
60.5
60
49.6
% of patients
50
45.6
40
35.4
32.5
30
28.1
26.5
21.2
20
15.4
15.2
11.6
10
2.4
2.8
5.3
3
0
5 mg 10 mg 15 mg 20 mg 5 mg 10 mg 20 mg 4 mg
Donepezil
Memantine
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
8 mg 16 mg 24 mg 3 mg
Galantamine
6 mg
9 mg 12 mg 4.6 mg 9.5 mg
Rivastigmine
oral
Rivastigmine
patch
25
Most physicians preferred transdermal therapy,
at Week 24
• Of 89 physicians, most indicated preference for transdermal therapy (n=71) over
oral therapy (n=18) at the end of study
Physicians preference
100
80
n=71
60
40
20
n=18
0
Oral monotherapy
Transdermal monotherapy
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
26
Most important reasons for physicians for preferring
transdermal therapy, at Week 24
n=24 33.8
Reasons for caregiver preference
Easier to use
n=14
Easier to comply/better acceptance by the patient
Easier to administer
n=13
More convenient/fits better into daily life
n=9
Other
n=6
Easier to follow medication scedule
n=3
Helps me feel more in charge of his/her care
n=1
1.4
Trust it more
n=1
1.4
0
19.7
18.3
12.7
8.5
4.2
10
20
% of responses
30
40
Information collected only once for each physician. This information is not collected at patient
level. Rank of reasons for preference in above graph: 1 = most important
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
27
Mini-Mental State Examination
• The mean increase in MMSE score from baseline to Week 24 was higher in the
transdermal cohort
Mean change from baseline to Week 24
1.6
1.4
1.4
n=648
1.2
1
0.8
0.6
0.5
n=653
0.4
0.2
Oral monotherapy
Transdermal monotherapy
MMSE rated from 0 to 30: 0-9=severe impairment, 10-20=moderate impairment, 21-24=mild impairment, 25-30=normal,
depending on age, education, complaints.
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
MMSE, Mini-Mental State Examination.
28
Caregiver Behavioral Assessment
Disorder
Oral monotherapy cohort
Transdermal monotherapy cohort
Mean Frequency
Mean Severity
Mean Frequency
Mean Severity
Delusions
Baseline
Week 24
0.63
0.57
1.88
1.59
0.66
0.45
1.80
1.46
Hallucinations
Baseline
Week 24
0.53
0.47
1.80
1.56
0.53
0.39
1.80
1.47
Anxiety
Baseline
Week 24
0.98
0.81
1.79
1.55
1.16
0.74
1.80
1.44
Agitation/ aggressivity
Baseline
Week 24
0.88
0.84
1.80
1.61
1.03
0.60
1.84
1.48
Apathy
Baseline
Week 24
0.57
0.59
1.59
1.58
0.77
0.59
1.68
1.47
Depression
Baseline
Week 24
0.96
0.82
1.80
1.55
1.14
0.74
1.88
1.41
Sleep disorder
Baseline
Week 24
1.03
0.80
2.02
1.74
1.17
0.69
2.03
1.61
29
Caregiver Behavioral Assessment by frequency,
at Week 24
•
Frequencies of disorders were lower at Week 24 in the transdermal monotherapy cohort
Sleep disorder
n=482
n=496
0.69
0.80
n=496
n=482
0.74
Depression
n=492
n=479
Apathy
0.59
0.59
n=498
Agitation/ aggressivity
n=485
0.82
0.84
0.60
n=496
0.81
n=482
0.74
Anxiety
n=497
0.39
n=482
Hallucinations
Delusions
0
0.1
0.2
0.3
0.47
0.57
n=483
n=497
0.45
0.4
0.5
0.6
0.7
0.8
0.9
Mean frequency at Week 24
Oral monotherapy
Transdermal monotherapy
Frequency rated from 0 to 4: 0=none, 1=rarely, 2=sometimes, 3=often, 4=very often.
30
Caregiver Behavioral Assessment by severity,
at Week 24
•
Severities of disorders were lower at Week 24 in the transdermal monotherapy cohort
n=198
Sleep disorder
n=188
n=218
n=214 1.41
Depression
1.74
1.61
1.55
n=160
1.58
n=164 1.47
Apathy
n=219
Agitation/ aggressivity
n=174
1.61
1.48
Anxiety
n=226
1.55
n=223 1.44
Hallucinations
n=127
1.56
1.47
n=110
1.59
n=154
n=127
1.46
Delusions
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
Mean severity at Week 24
Oral monotherapy
Transdermal monotherapy
Severity rated from 1 to 3: 1=slight, 2=moderate, 3=important.
31
Clinical Global Impression of Change
• Mean CGI-C score at Week 24 was lower in transdermal monotherapy cohort as
compared to oral monotherapy cohort
Mean CGI-C score at Week 24
4.5
4.0
4
n=51
3.5
3.5
n=48
3
2.5
2
1.5
1
Oral monotherapy
Transdermal monotherapy
CGI-C rated from 1 to 7: 1=marked improvement, 2=moderate improvement, 3=mild improvement, 4=no change, 5=mild
worsening, 6=moderate worsening, 7=marked worsening.
CGI-C, Clinical Global Impression of Change.
32
Alzheimer's Disease Cooperative Study – Activities of
Daily Living
Mean change from baseline to Week 24
• The decline in ADCS-ADL score was higher in patients under oral monotherapy
cohort
0
-0.4
n=39
-0.8
-0.9
-1.2
n=38
-1.6
n=38
-1.6
-2
Oral monotherapy
Transdermal monotherapy
ADCS-ADL rated from 0 to 78: 0=need for extensive help to 78=independent performance.
ADCS-ADL, Alzheimer's Disease Cooperative Study Activities of Daily Living.
33
Clinical Dementia Rating
• There was almost no change in the CDR scale for both treatment cohorts as
compared to baseline at end of study
Mean change from baseline to Week 24
0.12
0.1
0.1
n=160
n=123
0.08
0.04
0
Oral monotherapy
Transdermal monotherapy
CDR rated from 0 to 3: 0=normal, 0.5=very mild dementia, 1=mild dementia, 2=moderate dementia, 3=severe dementia.
CDR, Clinical Dementia Rating.
34
Global Deterioration Scale
• The transdermal monotherapy was more effective in preserving cognition
Mean change from baseline to Week 24
0.3
0.2
0.2
n=64
0.1
0
-0.1
-0.2
n=52
-0.3
-0.3
-0.4
Oral monotherapy
Transdermal monotherapy
GDS: Rated from 0 to 7 stages: 1=No cognitive decline, 2=very mild cognitive decline, 3=mild cognitive decline,
4=moderate cognitive decline, 5=moderately severe cognitive decline, 6=severe cognitive decline (middle dementia),
7=very severe cognitive decline (late dementia)
GDS, Global Deterioration Scale.
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Comparable proportion of serious adverse events were
observed in the two treatment cohorts
Summary of serious adverse events
Patients with SAE(s)
Injury, poisoning and procedural complications
Infections and infestations
Nervous system disorders
General disorders and administration site conditions
Neoplasms benign, malignant and unspecified
(including cysts and polyps)
Respiratory, thoracic and mediastinal disorders
Cardiac disorders
Psychiatric disorders
Gastrointestinal disorders
Investigations
Metabolism and nutrition disorders
Vascular disorders
Ear and labyrinth disorders
Musculoskeletal and connective tissue disorders
Renal and urinary disorders
Blood and lymphatic system disorders
Skin and subcutaneous tissue disorders
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
Oral
monotherapy
cohort
N=953
n (%)
Transdermal
monotherapy
cohort
N=978
n (%)
40 (4.2)
31 (3.2)
14 (1.5)
12 (1.3)
8 (0.8)
11 (1.1)
5 (0.5)
6 (0.6)
5 (0.5)
5 (0.5)
4 (0.4)
3 (0.3)
4 (0.4)
0
3 (0.3)
4 (0.4)
2 (0.2)
3 (0.3)
2 (0.2)
1 (0.1)
0
0
1 (0.1)
0
3 (0.3)
5 (0.5)
2 (0.2)
0
1 (0.1)
0
1 (0.1)
1 (0.1)
2 (0.2)
2 (0.2)
0
1 (0.1)
SAE, serious adverse event.
36
Adverse events causing discontinuation
Summary of adverse events causing discontinuation
Patients with AE(s)
Skin and subcutaneous tissue disorders
Gastrointestinal disorders
Nervous system disorders
Metabolism and nutrition disorders
General disorders and administration site
conditions
Psychiatric disorders
Vascular disorders
Ear and labyrinth disorders
Immune system disorders
Injury, poisoning and procedural complications
Investigations
Musculoskeletal and connective tissue disorders
Neoplasms benign, malignant and unspecified
(including cysts and polyps)
Renal and urinary disorders
Pai MC, et al. Clinical Interventions in Aging 2015:10 1779–1788
Oral
monotherapy
cohort
N=953
n (%)
Transdermal
monotherapy
cohort
N=978
n (%)
30 (3.1)
0
23 (2.4)
4 (0.4)
43 (4.4)
34 (3.5)
1 (0.1)
4 (0.4)
4 (0.4)
0
1 (0.1)
2 (0.2)
2 (0.2)
1 (0.1)
0
0
0
0
0
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
0
1 (0.1)
0
AE, adverse event.
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Summary
• Previous clinical study have demonstrated the efficacy and safety of rivastigmine
patch1
• RECAP study evaluated caregiver preference and compliance with oral and
transdermal medication in an ethnically diverse population of patients with mild-tomoderate Alzheimer's disease from Asia and Middle Eastern countries where there
is scarcity of such data2
• Data were pooled and analyzed from India, Egypt, South Korea, Taiwan, Lebanon
and Singapore2
– RECAP study showed higher caregiver and physician preference, and greater patient
compliance with transdermal therapy in daily practice2
– more patients were able to reach higher daily doses with the transdermal rivastigmine
monotherapy2
– concomitant psychotropic medication usage as well as the number of different
psychotropic medications per patient were similar between groups2
– comparable proportions of patients reported to have adverse events2
– discontinuation rate due to adverse events were low in both groups2
1. Winblad B, et al. Int J Geriatr Psychiatry 2007;22:456–467.
2. Kandiah N. Poster presented at: 26th AAIC; July 12–17, 2014; Copenhagen, Denmark.
38