The Effect of Vascular Risk Factors on the Efficacy of Rivastigmine Patch and Capsule Treatment in Alzheimer’s Disease

Farlow, Martin R.; Doraiswamy, P. Murali; Meng, Xiangyi; Cooke, Kathryn; Somogyi, Monique

doi:10.1159/000328745

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…It also changes the unfavorable ratio of AChE-R to AChE-S in the CNS [208,[217][218][219][220]. AD patients with vascular risk factors may demonstrate an altered response to rivastigmine treatment compared to AD patients without these risks (cognition and speech are particularly affected) [221].…”

Section: Drug Characteristics Disadvantagesmentioning

confidence: 99%

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Walczak-Nowicka

Herbet

2021

IJMS

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Acetylcholinesterase (AChE) plays an important role in the pathogenesis of neurodegenerative diseases by influencing the inflammatory response, apoptosis, oxidative stress and aggregation of pathological proteins. There is a search for new compounds that can prevent the occurrence of neurodegenerative diseases and slow down their course. The aim of this review is to present the role of AChE in the pathomechanism of neurodegenerative diseases. In addition, this review aims to reveal the benefits of using AChE inhibitors to treat these diseases. The selected new AChE inhibitors were also assessed in terms of their potential use in the described disease entities. Designing and searching for new drugs targeting AChE may in the future allow the discovery of therapies that will be effective in the treatment of neurodegenerative diseases.

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Section: Drug Characteristics Disadvantagesmentioning

confidence: 99%

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Walczak-Nowicka

Herbet

2021

IJMS

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“…On the ADCS-ADL, a responder can be defined as a patient who improves or is stabilized in the course of a randomized clinical trial. It is also important to identify factors that may influence the likelihood of receiving a benefit from treatment, as patients may vary in their response to treatment according to their clinical characteristics [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch

et al. 2015

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IntroductionOPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer’s disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer’s disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch.MethodsUsing OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. ‘Improvers’ were patients who improved on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale (ADCS-IADL). ‘Non-decliners’ were patients who did not decline on either scale.ResultsOverall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were ‘improvers’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were ‘non-decliners’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48.ConclusionMore patients with mild-to-moderate Alzheimer’s disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are ‘improvers’ or ‘non-decliners’ i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch.Trial registrationClinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-014-0088-8) contains supplementary material, which is available to authorized users.

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“…In fact, one previous randomized trial has indicated that following rivastigmine treatment for 26 weeks, patients with AD with vascular risk factors (VRFs) showed greater clinical benefit in cognition, activities of daily living, and disease severity than those with AD without VRFs [ 15 ]. Another recent retrospective analysis of a large international 24-week multicenter randomized double-blind placebo-and active-controlled trial also indicated the significant impact of VRF status on treatment response in AD [ 16 ]. In these studies, however, VRFs were determined using only the Modified Hachinski Ischemic Score (HIS) [ 17 ] or by assessing the presence or absence of reported VRFs at the time of screening.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer’s dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial

et al. 2017

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Background and objectiveStudies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer’s disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs.MethodsThree hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study.ResultsOf the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups.ConclusionsAlthough the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs.Trial registrationClinicalTrials.gov NCT01380288

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The Effect of Vascular Risk Factors on the Efficacy of Rivastigmine Patch and Capsule Treatment in Alzheimer’s Disease

Cited by 8 publications

References 35 publications

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer’s dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial

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