28. BREXPIPRAZOLE FOR AGITATION ASSOCIATED WITH DEMENTIA DUE TO ALZHEIMER’S DISEASE: NUMBER NEEDED TO TREAT, NUMBER NEEDED TO HARM, AND LIKELIHOOD TO BE HELPED OR HARMED

Introduction

Agitation is a prevalent, highly distressing and burdensome neuropsychiatric symptom of Alzheimer’s disease. In this vulnerable patient population, it is especially critical to maximize benefits, minimize risks, and understand expected treatment outcomes. This analysis delineates the clinical benefit and risk profile of brexpiprazole in patients with agitation associated with dementia due to Alzheimer’s disease, using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Methods

Data are pooled from two fixed-dose pivotal clinical trials of brexpiprazole in patients with agitation associated with dementia due to Alzheimer’s disease (NCT01862640 [Trial 283], NCT03548584 [Trial 213]), and analyzed for brexpiprazole 2 or 3 mg/day (FDA-approved recommended-to-maximum dose) versus placebo. In both trials, the Cohen-Mansfield Agitation Inventory (CMAI) was the primary efficacy measure. For this post hoc analysis, the main efficacy outcome was agitation response rate, defined as ≥20-point reduction in CMAI Total score from baseline to Week 12. Previous analyses indicate that a 20-point within-person CMAI reduction reflects a clinically meaningful benefit in this population. The main safety outcome was incidence of discontinuation due to treatment-emergent adverse events (TEAEs). Other efficacy and safety outcomes were also analyzed. For the identified outcomes, NNT, NNH and LHH were calculated. NNT and NNH indicate how many patients would need to be treated with brexpiprazole versus placebo in order for one additional patient to experience a benefit (NNT) or a harm (NNH). LHH is the ratio of NNH to NNT. Lower NNT values, and higher NNH and LHH values, are more supportive of brexpiprazole versus placebo.

Results

Response rates (≥20-point CMAI Total reduction) were 50.1% (182/363) for brexpiprazole, and 37.7% (93/247) for placebo, yielding a NNT of 9 (95% confidence internal [CI]: 5, 22). The incidence of discontinuation due to TEAEs was 4.9% (18/366) for brexpiprazole, and 4.8% (12/251) for placebo, yielding a NNH of 730 (95% CI: not significant). Together, these specific outcomes result in a LHH of 81.

Conclusions

Brexpiprazole is 81 times more likely to result in treatment response (as defined by a ≥20-point reduction in CMAI Total score) than discontinuation because of a TEAE. This analysis provides meaningful clinical interpretation of benefits and risks of brexpiprazole in patients with agitation associated with dementia due to Alzheimer’s disease. These data expand the evidence-base for brexpiprazole, and underscore the favorable efficacy and safety profile that supports the use of brexpiprazole in this patient population.

This abstract was submitted at the late-breaker deadline to allow sufficient time to discuss the methodology, and ultimately ensure that clinically relevant outcomes were selected.