Comparative Effectiveness of Oral and Long-acting Injectable Antipsychotics in Schizophrenia: A Real-world Study in the US Medicare Population

Abstract: Objective: Long-acting injectables (LAIs) may provide an advantage over daily oral antipsychotics (OAPs), but little real-world evidence exists in the Medicare population, which includes about half of US patients with schizophrenia. This study compared the effectiveness of LAIs and OAPs across different agents and dosing intervals. Methods: National fee-for-service Medicare claims from 2006-2019 were used to identify all beneficiaries with schizophrenia and ≥1 antipsychotic fill. The primary outcome was treatment failure, a composite measure of psychiatric hospitalization, antipsychotic discontinuation, suicide attempt, or death. Within-individual Cox regressions were used, in which each individual served as his or her own control to remove selection bias. We first compared outcomes across all LAI and OAP agents using aripiprazole LAI as the comparator. Next, we separated the LAI agents by dosing intervals with aripiprazole LAI every 1-month as the comparator. Results: The final sample included 152,835 beneficiaries (mean age 53.5 years, 54.0% male, 61.5% White). Compared to aripiprazole LAI, all OAPs except clozapine and all LAIs except risperidone (HR 0.92; 95%CI 0.87-0.98) and paliperidone (HR 0.88; 95% CI 0.83-0.93) were associated with a significantly higher hazard (HRs 1.12 to 1.77) of treatment failure. When separating LAI agents by dosing interval, paliperidone LAI every 3-months (HR 0.62; 95% CI 0.55-0.71) had the lowest hazard of failure. Conclusions: This real-world study found that all OAPs except clozapine had a higher risk of treatment failure relative to aripiprazole LAI. Several LAIs showed a greater benefit with paliperidone LAI every 3-months having the lowest risk of treatment failure.Short Description: This real-world study used 2006-2019 national fee-for-service Medicare claims data to compare the effectiveness of long-acting injectables (LAIs) and daily oral antipsychotics (OAPs) among patients with schizophrenia. The analysis revealed that all OAPs except clozapine had a higher risk of treatment failure relative to aripiprazole LAI. Several LAIs showed a greater benefit; paliperidone LAI every 3-months had the lowest risk of treatment failure relative to aripiprazole LAI.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC