Authors: Bullock, Roger¹; Touchon, Jacques²; Bergman, Howard³; Gambina, Giuseppe⁴; He, Yunsheng⁵; Rapatz, Günter⁶; Nagel, Jennifer⁶; Lane, Roger⁵

Source: Current Medical Research and Opinion, Volume 21, Number 8, August 2005 , pp. 1317-1328(12)

Publisher: Informa Healthcare

Abstract:

Objectives: Randomised controlled trials that directly compare cholinesterase inhibitors for the treatment of Alzheimer's disease have been characterised by significant methodological limitations. As a consequence, they have failed to establish whether there are differences between agents in this class. To help address this question, a double-blind, randomised, controlled, multicentre trial was designed to evaluate the efficacy and tolerability of cholinesterase inhibitor treatment in patients with moderate to moderately-severe Alzheimer's disease over a 2-year period.

Methods: Patients were randomly assigned to rivastigmine 3–12mg/day or donepezil 5–10mg/day. Efficacy measures comprised assessments of cognition, activities of daily living, global functioning and behavioural symptoms. Safety and tolerability assessments included adverse events and measurement of vital signs.

Results: In total, 994 patients received cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499), and 57.9% of patients completed the study. The most frequent reason for premature discontinuation in both treatment groups was adverse events, primarily gastrointestinal. Adverse events were more frequent in the rivastigmine group during the titration phase, but similar in the maintenance phase. Serious adverse events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated patients, respectively. Rivastigmine and donepezil had similar effects on measures of cognition and behaviour, but rivastigmine showed a statistically significant advantage on measures of activities of daily living and global functioning in the ITT–LOCF population. However, this was not maintained in the non-ITT–LOCF populations. In secondary subgroup analyses, AD patients who had genotypes that encoded for full expression of the butyrylcholinesterase enzyme (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed significantly greater benefits from rivastigmine treatment.

Conclusions: Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up to 2 years in patients with moderate AD. Although both drugs performed similarly on cognition and behaviour, rivastigmine may provide greater benefit in activities of daily living and global functioning.

Keywords: ALZHEIMER'S DISEASE; CHOLINESTERASE INHIBITORS; DONEPEZIL; DOUBLE-BLIND RANDOMISED CONTROLLED TRIAL; RIVASTIGMINE

Document Type: Research article

DOI: http://dx.doi.org/10.1185/030079905X56565

Affiliations: 1: Kingshill Research Centre, Swindon, UK 2: CHU Hôpital Guy de Chauliac, Montpellier, France 3: McGill University, Montreal, Quebec, Canada 4: Ospedale Civile Maggiore, Verona, Italy 5: Novartis Pharmaceuticals, East Hanover, NJ, USA 6: Novartis Pharma AG, Basel, Switzerland

Publication date: 2005-08-01

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