AT THE ICSR BIENNIAL MEETING
COLORADO SPRINGS (FRONTLINE MEDICAL NEWS) – The once monthly long-acting injectable formulation of the atypical antipsychotic aripiprazole was superior to a similar formulation of paliperidone palmitate in health-related quality-of-life scale total scores in people with schizophrenia, new data show.
The primary results in the head-to-head trial were supported by a significant decrease in Clinical Global Impression Scale (CGI-S) scores, better tolerability, and less treatment-related adverse events.
“The field has longed for such trials that fairly compare available treatments. Both treatments were effective, but aripiprazole once monthly was more effective across almost all measures,” Dr. Steven G. Potkin, the Robert R. Sprague Chair in Brain Imaging and a professor of psychiatry at the University of California, Irvine, and a lead author on the study, said in an interview.
Data from the QUALIFY study were presented at the biennial meeting of the 15th International Congress on Schizophrenia Research.
According to Dr. Potkin, the study is the first to use the quality of life scale to compare the effects of two, once-monthly, long-acting injectables (LAIs) with different modes of action in schizophrenia to determine treatment effects on patients’ overall social experience, work capacity, sense of purpose, curiosity, empathy, motivation, and level of presence in the community.
“The study has meaningful clinical impact, as it addresses some of the more important concerns that individuals with schizophrenia face such as ability to socialize and interact with others,” Dr. Potkin said.
In this phase IIIb, multicenter, international 28-week, randomized, open-label, rater-blinded, parallel group study, Dr. Potkin and his colleagues randomly assigned 295 adults with schizophrenia who were switching form an oral antipsychotic to an injectable one, to receive either the partial dopamine D2 agonist aripiprazole once monthly 400 mg or the dopamine D2 antagonist paliperidone palmitate at equivalent flexible dosing equivalent of 50 mg to 150 mg per month in the European Union and Canada, or 78 mg to 234 mg per month in the United States.
Patients were stable at baseline. Nearly 60% were male, and 44% were obese. Mean age was 42 years. Baseline quality of life scale (QLS) scores for the 148 individuals in the aripiprazole arm were 66.1 (standard deviation, 21.4) and 62.5 (SD, 21.3) for the 147 persons in the paliperidone palmitate arm. The baseline CGI-S scores for both groups was 4.0. Patients were assessed every 4th week.
By week 28, 100 in the aripiprazole arm completed treatment, and 83 completed treatment in the paliperidone palmitate arm.
The mean doses at week 24 were 387.0 +/– standard equivalent 3.4 mg for aripiprazole and 110.3 +/– 3.6 mg for paliperidone palmitate for the E.U. and Canada. The U.S. equivalent was 172 mg.
The primary endpoint of QLS scores at week 28 demonstrated the noninferiority and superiority of once-monthly aripiprazole over paliperidone palmitate. The aripiprazole arm improved QLS scores by 7.47 (SD, 1.53) compared with 2.80 (SD, 1.62) in the other group. The least square mean difference between treatments was 4.67 (95% confidence interval, [0.32; 9.02]; P = .036).
“The study was designed as a noninferiority trial, that is, to determine if aripiprazole 400 mg once monthly was as good as paliperidone palmitate,” Dr. Potkin said. “Not only was the aripiprazole as good as paliperidone palmitate, but indeed it was superior in the important health-related quality of life measures.”
Aripiprazole also significantly bested paliperidone palmitate in the secondary endpoint of improvements in the CGI-S score: –0.75 (SD, 0.07), compared with –0.46 (SD, 0.07). The least square mean difference between treatment was –0.28 (95% CI [–0.48; –0.09]; P = .004).
Adverse events assessed during the oral conversion, LAI-initiation, and LAI-continuation phases were more common in the paliperidone palmitate group during all phases but the initiation phase (51 reported events vs. 55 in the aripiprazole group). Significant adverse events were more common in the paliperidone palmitate group during the continuation phase (8 events vs. 6), and treatment-related adverse events leading to discontinuation of therapy during the continuation phase occurred in 13 of the paliperidone palmitate group vs. 6 in the aripiprazole group.
Insomnia was reported in both groups across all phases, as was weight gain, which was more common in the paliperidone palmitate group during the continuation phase (17 vs. 12).
“The study design represents the choice that clinicians face when deciding which atypical long-acting formulation to recommend to which patient,” Dr. Potkin said. “What I think is clinically relevant is that the primary outcome measure was the patient’s quality of life that includes the patient’s negative symptoms such as lack of empathy, motivation, curiosity, and socialization, and the consequence of these symptoms on everyday functioning. These symptoms are the most important to patients and their loved ones once the initial acute symptom episode has been stabilized.”
This trial was underwritten by Otsuka, makers of Abilify Maintena, and by H. Lundbeck A/S. Dr. Potkin is on the speakers bureau for Otsuka, Forest, and Sunovion, and serves on advisory boards of Alkermes, Forest, Genetech, Lundbeck, Otsuka, Roche, Sunovion, and Takeda.
wmcknight@frontlinemedcom.com On Twitter @whitneymcknight
