Aripiprazole Lauroxil Every 2 Months for the Treatment of Adults With Schizophrenia: A Post Hoc Analysis of Efficacy by Baseline Severity of Illness From Phase 3b Clinical Trial Data.

Background: This post hoc analysis examined the efficacy of aripiprazole lauroxil (AL) by baseline severity of illness in the double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness study (NCT03345979) in patients with schizophrenia treated with AL every 2 months. Study Methods: Adults with acute schizophrenia were randomized to AL 1064 mg every 2 months or active control (paliperidone palmitate [PP] 156 mg monthly). Based on Clinical Global Impression-Severity scores, baseline severity of illness was categorized as moderate, marked, or severe. Changes from baseline in Positive and Negative Syndrome Scale (PANSS) Total score were assessed at week 25, along with PANSS items related to hostility/excitement. Numbers of patients with activation adverse events (AEs; anxiety, agitation, and insomnia) were also evaluated. Study Results: Of 99 patients assigned to AL, 31 (31%) were moderately ill at baseline, 54 (55%) were markedly ill, and 14 (14%) were severely ill. With AL treatment, mean ± SE changes from baseline in PANSS Total score at week 25 were -21.1 ± 2.5 (moderately ill; baseline, 87.1), -24.1 ± 1.8 (markedly ill; baseline, 95.3), and -25.6 ± 6.4 (severely ill, baseline, 106.1). Improvements from baseline in PANSS scores related to hostility/excitement items were comparable among severity subgroups. No clear pattern of occurrence of the AEs anxiety, agitation, and insomnia was observed across baseline severity groups. Conclusions: In this post hoc analysis, safety related to activation and efficacy with AL treatment were comparable across baseline severity-of-illness subgroups of patients with schizophrenia.