Long-acting antipsychotics safe, effective for in-hospital schizophrenia therapy initiation

Aristada Initio and Invega Sustenna appeared well tolerated and effective for initiating in-hospital schizophrenia treatment and continuing outpatient treatment, according to a study published in Journal of Clinical Psychiatry.

Amy Claxton

“The approval of aripiprazole lauroxil [Aristada Initio, Alkermes] was based on a 12-week study that evaluated 441 mg and 882 mg monthly doses of [the treatment] compared with placebo,” Amy Claxton, PhD, director of clinical research at Alkermes, told Healio Psychiatry. “The 1-day initiation regimen consisting of Aristada Initio 675 mg and one single dose of 30 mg of oral aripiprazole, and the 1,064 mg 2-month dose interval Aristada Initio option were approved by the FDA based upon pharmacokinetic studies. The Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study provided the first clinical efficacy and safety data for both the 1-day Aristada Initio initiation regimen and the 2-month dose interval Aristada Initio option among adults with schizophrenia who were hospitalized for an acute exacerbation of schizophrenia.”

Claxton and colleagues used Invega Sustenna (paliperidone palmitate, Janssen Pharmaceuticals) as an active control in the ALPINE study, which allowed them to avoid using a placebo among patients with schizophrenia.

Prior studies have shown that long-acting injectable (LAI) antipsychotics are underused as schizophrenia treatments, with one potential treatment barrier being that LAI initiation can prove challenging in acute inpatient settings given short lengths of stay, the researchers noted. However, the LAI Aristada Initio allows patients started on this regimen to be discharged without needing antipsychotic dosing for 2 months.

In the phase 3, randomized, double-blind, active-control ALPINE study, Claxton and colleagues sought to evaluate safety and efficacy of a 2-month formulation of Aristada Initio with 1-day initiation during hospitalization for acute exacerbation of schizophrenia followed by transition to outpatient care. They conducted the study from November 2017 to March 2019 and included 200 adults with acute schizophrenia according to DSM-5 criteria. They randomly assigned patients to Aristada Initio or Invega Sustenna for 25 weeks, and patients remained hospitalized for 2 or more weeks after randomization per protocol. Within-group change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to 4 weeks served as the primary endpoint. The researchers included within- and between-group changes from baseline at various time points in the secondary analyses and monitored adverse events and laboratory data.

Results showed a baseline PANSS total score of 94.1 for Aristada Initio, and scores were reduced by 17.4 points (P < .001) at 4 weeks, 19.8 points at 9 weeks and 23.3 points at 25 weeks. Patients who received Invega Sustenna exhibited significant reductions in PANSS total score from baseline of 20.1 points (P < .001) at 4 weeks, 22.5 points at 9 weeks and 21.7 at 25 weeks. Among the Aristada Initio group and Invega Sustenna groups, the most common adverse events over 25 weeks were injection site pain (17.2% and 24.8%, respectively), increased weight (9.1% and 16.8%) and akathisia (9.1% and 10.9%).

“The ALPINE study provides clinical evidence supportive of the pharmacokinetic studies on which the Aristada Initio 1-day initiation regimen, as well as the 2-month 1,064 mg dosing regimen, were approved,” Claxton told Healio Psychiatry. “These data are informative on treatment of schizophrenia with LAI antipsychotic regimens from acute hospitalization of markedly ill patients through transition to outpatient care in the community.” – by Joe Gramigna

Disclosures: Claxton reports being an employee of Alkermes Inc. Please see the study for all other authors’ relevant financial disclosures.