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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. 35 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. 37 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