Solanezumab does not slow cognitive or functional decline in persons with amyloid deposition but normal cognition

Reference

Sperling RA, Donohue MC, Raman R, et al, for the A4 Study Team. Trial of solanezumab in preclinical Alzheimer's disease. N Engl J Med 2023;389(12):1096-1107.

Synopsis

These researchers identified adults aged 65 to 85 years with a score of 0 on the 3-point Clinical Dementia Rating (CDR) scale, a Mini-Mental State Examination (MMSE) score of 25 to 30 consistent with no worse than mild impairment, and a Wechsler Memory Scale score of 6 to 18 (range 0 - 25; lower scores are worse). In summary, these patients had largely normal cognition with some evidence of memory impairment. Roughly one-quarter of those screened had brain amyloid on imaging, and these 1169 patients were randomized to receive solanezumab 400 mg intravenously per month or matching placebo. The dose was increased approximately halfway through the study (to 1600 mg intravenously per month) based on the results of another study, and the length of the trial was extended to allow "substantial exposure" to the higher dose for all participants. The mean age of participants was 72 years, 59% were women, 94% were White, and they had a mean of 16.6 years of education. After 4.5 years, the number of dropouts was similar between groups, with 401 participants in the solanezumab group and 425 in the placebo group left for the modified intention-to-treat analysis. After 4.5 years, there were no statistically or clinically significant differences between groups on the Preclinical Alzheimer Cognitive Composite score, the MMSE, the CDR, or any other scale. There were 6 deaths in the solanezumab group and 5 in the placebo group, and serious adverse events were similar between groups.