Monthly injections of paliperidone palmitate showed prolonged efficacy compared with daily oral antipsychotics in a new trial involving a group of schizophrenia patients who rarely participate in clinical research.
“A demographic that’s almost always excluded is people with a history of incarceration,” said lead author Dr. Larry Alphs, psychiatry therapeutic team leader at Janssen Scientific Affairs in Titusville, New Jersey.
“They were included in this trial,” he told Reuters Health. “That was exciting, because nobody’s done it before, and it’s a huge segment of the schizophrenia population.”
Dr. Alphs and colleagues published the results of the 15-month Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) trial in online April 14 in the Journal of Clinical Psychiatry. The researchers recruited 450 patients with schizophrenia from 50 sites in 25 U.S. states and Puerto Rico.
“To enhance enrollment of subjects often excluded from trials, efforts were made to recruit subjects from nontraditional locations, such as homeless shelters, soup kitchens, and jail-release or diversion programs,” the researchers write.
The major criterion for participation was having been in custody of the criminal justice system two or more times in the previous two years and having been released from custody within 90 days of the screening visit.
The researchers randomized the participants to receive either monthly injections of 78-234 mg paliperidone palmitate (n=230) or an oral antipsychotic randomly selected from a group of seven such drugs (n=220).
Forty percent of the paliperidone group and 54% of the oral antipsychotics group experienced treatment failure, the primary endpoint. The most common treatment failures were reincarceration and psychiatric hospitalization.
Paliperidone palmitate delayed the time to treatment failure significantly compared with oral antipsychotics (hazard ratio, 1.43; p=0.011), with a median time to first failure of 416 days versus 226 days.
Sixty participants were lost to follow-up and 42 withdrew from the study, leaving 305 participants who either had a first treatment failure or completed the study.
The five most common treatment-related adverse events were injection site pain, insomnia, weight gain, akathisia and anxiety.
“In the United States, the criminal justice system has become a frequent setting for management of patients with severe mental illness. It has overtaken psychiatric hospitals as a site for their institutionalization,” the researchers write.
The mechanism for prolonging treatment effect with paliperidone palmitate remains unclear. “We speculate that treatment with paliperidone palmitate leads to more consistent treatment exposure, resulting in fewer symptoms that lead to treatment failure,” the researchers write.
Paliperidone palmitate (Invega Sustenna, Janssen) already is approved for treatment of schizophrenia, and Janssen has applied for a label change to include the clinical trial results.
PRIDE “is a unique trial. We’re very excited and proud of it from that aspect,” Dr. Alphs told Reuters Health. “We tried to include more real-world patients and not those who are medically very stable and otherwise healthy people.”
“We were actually able to show a difference in outcomes between the long-acting injectable and the oral medications,” he continued. “That difference was actually quite large, in terms of delaying time to treatment failure in this study. The other thing that was impressive is that most of the outcomes that we saw were outcomes of very important public health impact,” hospitalization or incarceration.
Janssen Scientific Affairs funded this research. Six coauthors are employees of Janssen business units and one coauthor is a consultant for Janssen.