Two-year treatment of Alzheimer's disease with eptastigmine

The effectiveness of long-term treatment of Alzheimer's disease with cholin esterase inhibitors is a matter of controversy. We evaluated the effects of prolonged treatment with eptastigmine in 176 patients with mild to moderat e Alzheimer's disease participating in the open-label extension phase of a 25-week double-blind, placebo-controlled trial of eptastigmine. The effects of eptastigmine on cognition and daily functioning were evaluated with the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-Cog) a nd the Instrumental Activities of Daily Living (IADL) scale, respectively. Safety was monitored by physical examination, laboratory tests, vital funct ions and electrocardiogram measurements and by the assessment of adverse ev ents. One hundred and fifty-three patients (87%) completed 1 year of treatm ent 77 patients (44%) 18 months and 33 patients (19%) 2 years of treatment. Patients treated for 2 years showed an improvement of mean ADAS-Cog scores compared to baseline for 31 weeks and mean IADL scores remained close to b aseline for 25 weeks. Cognitive and functional scores then worsened as expe cted in this progressive disease. After 2 years, patients deteriorated comp ared to baseline by 13.4 points on the ADAS-Cog and 6.1 points on IADL. His torical untreated controls with identical disease severity are expected to have an annual worsening of approximately 10.9 points on ADAS-Cog and 4.9 p oints on IADL. Thus patients treated with eptastigmine for 2 years had a be nefit of 8.5 points on ADAS-Cog and 3.8 points on IADL. These benefits tran slate to about 9 months difference between eptastigmine-treated patients an d untreated historical patients. The drug was generally well tolerated with 14 patients (7.9%) withdrawing due to adverse events. Adverse events, not necessarily drug-related, were recorded in 66 patients (37.5%) and were tra nsient and generally mild in severity. This study indicates that prolonged treatment with eptastigmine is safe and produced a clinically long-term ben efit in patients with Alzheimer's disease.