Objective: Beyond 6 to 9 months of treatment with cholinesterase inhibitors (ChE-Is), there is a notable increase in the rate of cognitive decline in Alzheimer disease (AD) patients, and there are few longer-term studies to evaluate this finding. The authors examined whether the ChE-I rivastigmine continued to be therapeutically effective after up to 2 years of treatment in 2,010 patients with probable AD.
Methods: The clinical course of AD patients treated with rivastigmine was compared with a prediction of their course derived by a baseline-dependent historical model of disease progression developed from data in untreated AD patients. Rivastigmine efficacy data came from four 6-month, placebo-controlled, randomized, controlled trials (RCTs) and two open-label extension studies. Cognitive performance was assessed by various clinician- and caregiver-rated measures.
Results: After 2 years on rivastigmine, there was less cognitive deterioration than in historical-control subjects. These effects of rivastigmine on cognitive performance were considered clinically meaningful relative to expected global decline. Treatment-emergent adverse events were the commonly-seen side effects of ChEIs and were similar in frequency to those seen in patients assigned to shorter-term rivastigmine therapy.
Conclusion: Rivastigmine had a beneficial effect on cognitive performance for up to 2 years in patients with AD, versus no treatment or placebo treatment in historical-control subjects. Caregiver and clinician assessments indicated that the cognitive performance findings were of a magnitude relevant to global patient functioning. Rivastigmine remained safe over this 2-year treatment period.