PODCAST: Navigating treatment choice for patients with schizophrenia
SUBSTANTIATING DATA
P Values for comparative studies mentioned in this interview
In a meta-analysis (reported in Correll et al. 2016)8, combined brexpiprazole 2mg and 4 mg were statistically significantly superior to placebo on the primary efficacy endpoint: change from baseline at week 6 in PANSS total score (least square mean difference from placebo: −5.46, p=0.0004, and −6.69, p<0.0001, respectively). In both groups, a statistically significant treatment effect compared to placebo was apparent at week 1 (p<0.05 for both groups). In one of the individual studies included in this meta-analysis (reported in Kane et al. 2015), the 2 mg group did not statistically significantly separate from placebo on the primary efficacy endpoint.4
In the same meta-analysis, secondary endpoints included:
• Combined brexpiprazole 2mg and 4 mg were statistically significantly superior to placebo on the change from baseline at week 6 in in the five PANSS Marder factor scores (p<0.05 for both groups on each score)
• Combined brexpiprazole 2mg and 4 mg led to a statistically significant improvement in the Personal and Social Performance (PSP) total score compared to placebo at week 6 (p<0.05 for both groups).
A long-term (52 weeks) relapse prevention study (reported in Fleischhacker et al. 2017 and supplement)5 showed that time to impending relapse was statistically significantly delayed with brexpiprazole treatment compared with placebo (p< 0.0001, log-rank test). The hazard ratio for the final analysis was 0.292 (95% confidence interval: 0.156, 0.548) [Brexpiprazole reduced the risk of impending relapse by 71% vs placebo]. Prior to this double-blind, placebo-controlled maintenance phase, patients completed a 12- to 36-week stabilization phase. In the stabilization phase, there was a mean decrease (improvement) in PANSS total score of 15.13 points from baseline to last visit (p value not reported).
Efficacy was demonstrated at a prespecified interim analysis (conducted after 45 events), and so the trial was terminated early (reported in Fleischhacker et al. 2017).
P values were not reported for the quoted tolerability outcomes.
The percentage of subjects in the pivotal short-term trials who had a potentially clinically relevant increase in body weight (≥7%) was 10.5% and 10.2% in the REXULTI 2 mg and 4 mg/day groups, respectively, compared with 4.1% in the placebo group.3