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ORLANDO, FL — Aripiprazole lauroxil (AL), a long-acting injectable medication approved for the treatment of schizophrenia, was shown to be an effective, well-tolerated, long-term treatment in patients with schizophrenia, according to a post hoc analysis presented at US Psych Congress 2018, October 25 to 28 in Orlando, Florida.
“One of the challenges in long-term studies of oral antipsychotics for the treatment of schizophrenia is that safety and symptom outcomes may potentially be confounded by covert nonadherence . . . the ability to monitor adherence of a [long-acting injectable] like AL provides an opportunity to assess safety and symptom outcome trajectories unaffected by covert nonadherence that may potentially occur with the oral route.”
Researchers prefaced the study with a 12-week, randomized, placebo-controlled, double-blind efficacy trial (NCT01626456), then followed up with a phase 3, 52-week, multicenter long-term safety study (NCT01895452) through which they evaluated the long-term safety and durability of the medication.
Patients included in the 52-week study were age 18 to 70 years and had clinically stable disease when they entered the study. Of the patients who were receiving a first-line oral antipsychotic, 24% (n=103) were given 441 mg of AL, and the remainder (n=329) were given 882 mg of AL in fixed doses every 4 weeks.
At 24 weeks of treatment, the estimated probability of all-cause discontinuation was approximately 18%, and for medication-related discontinuation the probability was approximately 4%.
Results were assessed over the course of 112 weeks of follow-up by time to all-cause and medication-related discontinuations using the Kaplan-Meier method. The safety of the medication was monitored by adverse events (AEs) over 168 weeks, and the trajectory of clinical symptoms and illness severity was assessed using the Positive and Negative Syndrome Scale total and Clinical Global Impression-Severity scores.
AEs were reported in 45.1% (n=195) of patients, with 90.8% (n=177/195) of all AEs being mild or moderate in intensity. The most frequently reported AEs were insomnia (7.2%), headache (5.3%), and anxiety (5.3%).
Of the 432 patients included in the post hoc analysis, 60% (n=259) remained to the end of the long-term extension. In total, 77.8% (n=336) of patients received at least 12 injections, and 61.6% (n-266) received at least 24 injections during the post hoc analysis period. The overall all-cause hospitalization rate over 168 weeks was 4.9% (n=21/432), which included 3.9% (n=4/103) of patients from the AL 441 mg group and 5.2% (n=17/329) of patients from the AL 882 mg group. There were 17 AEs and 8 serious AEs among the participants.
Study limitations included the inability to accommodate dose adjustments over the course of the study, as well as the limited generalizability of study results considering the inclusion of patients who successfully completed the initial 12-week efficacy study.
“This post hoc analysis demonstrates the safety and continued therapeutic efficacy of long-term treatment with AL in patients with schizophrenia,” the researchers concluded. They also noted that dosage did not appear to affect the trajectory of symptom changes over the course of 2-year follow-up, and that AL was well tolerated with a safety profile consistent with results from their initial 52-week study.
Disclosures: PJW, AC, and YD are all employees of Alkermes, Inc. JL has served as an advisory board member for Otsuka and Alkermes, and on an event monitoring board for Alkermes. This study was funded by Alkermes, Inc. Medical. Writing support was provided by Karen Yee, PhD (ApotheCom, UK), and was funded by Alkermes, Inc.
Weiden PJ, Claxton A, Du Y, Lauriello J. Long-term outcomes with aripiprazole lauroxil for the treatment of schizophrenia: A 1-year, phase 3, multicenter extension study.. Presented at: US Psych Congress 2018; October 25-28, 2018; Orlando, FL. Poster 234.