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

Abstract

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.

Evaluating Response to High‐Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's Disease

“…Gender was found to be a significant predictor of “improvement” at Week 48, but not Week 24, in the OPTIMA study . As noted above, in the current analysis, neither gender, time since the first symptoms of AD, BMI, nor concomitant memantine use was shown to predict “improvement” or “improvement or no change” on the ADCS‐CGIC at Week 24.…”

“…In this analysis, treatment with 13.3 mg/24 h rivastigmine patch and MMSE score were significant predictors of improvement (≥4‐point improvement on the Alzheimer's Disease Assessment Scale–cognitive subscale and no change on the Alzheimer's Disease Cooperative Study–ADL scale) or no decline at Week 24 . Treatment with 13.3 mg/24 h rivastigmine patch was also a significant predictor of improvement, and MMSE score of no decline, at Week 48 . The current findings suggest that as well as being a predictor of response in patients with mild‐to‐moderate AD, treatment with 13.3 mg/24 h rivastigmine patch may also be relevant at severe disease stages.…”

“…Post hoc responder analyses have been performed on data from the OPTIMA (OPtimizing Transdermal Exelon study In Mild‐to‐moderate Alzheimer's disease) study, a 48‐week, double‐blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild‐to‐moderate AD who demonstrated decline on the 9.5 mg/24 h patch dose . In this analysis, treatment with 13.3 mg/24 h rivastigmine patch and MMSE score were significant predictors of improvement (≥4‐point improvement on the Alzheimer's Disease Assessment Scale–cognitive subscale and no change on the Alzheimer's Disease Cooperative Study–ADL scale) or no decline at Week 24 . Treatment with 13.3 mg/24 h rivastigmine patch was also a significant predictor of improvement, and MMSE score of no decline, at Week 48 .…”

Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System

“…Regional dominance of IL-34-(turquoise shaded areas) and CSF-1-(purple) mediated signals is indicated [7,8,28,30]. CSF-1 levels are upregulated in response to tissue injury and could drive the rapid expansion of microglia (M3 activation) [58,98]. Similarly,IL-34 promotes microglial expansion and neuroprotective microglial responses to viral infection [7].…”

Characteristics of the clinical picture and treatment of moderate or severe Alzheimer’s disease

“…Пациенты, у которых на фоне применения пластыря 9,5 мг/сут через 6-12 мес были отмече-ны клиническое ухудшение, были рандомизиро-ваны в слепую фазу -280 человек были переведе-ны на дозу ривастигмина 13,3 мг/сут, а 287 оста-лись на дозе 9,5 мг/сут [15]. При применении пла-стыря с большей дозой ривастигмина (13,3 мг) было отмечено достоверное замедление скорости функционального снижения согласно оценке по шкале функциональной активности (ADSCiADL), а также более пологая кривая когнитивно-го снижения, особенно по субшкале «память» [16][17][18]. Несмотря на то что количество гастроин-тестинальных побочных явлений оказалось не-сколько выше при применении более высоких доз, процент выхода из исследования в группе больных, применявших ТТС 15 см 2 , был даже ни-же, чем в группе применявших ТТС 9,5 мг/сут (9,6% против 12,7%), что свидетельствует о более высоком «удержании» на терапии при использо-вании высоких доз (своеобразный коэффициент «риск-польза») [16,19].…”