Efficacy and Safety of Early Use of Long-Acting Injectable Paliperidone Palmitate Versus Oral Antipsychotics in Patients With Schizophrenia: A Duration of Illness Meta-Analysis

Abstract: Background: Although long-acting injectable antipsychotics (LAIs) are often reserved for patients with chronic schizophrenia, emerging evidence suggests that LAIs may reduce the risk of treatment failure (TF) or relapse in patients with shorter duration of illness. Methods: This patient-level meta-analysis of the PRIDE (NCT01157351), PROSIPAL (NCT01081769), and DREaM (NCT02431702) studies evaluated the risk of TF with paliperidone palmitate (PP, once-monthly or once-every-3-months) LAI versus oral antipsychotic (OAP) treatment in patients with schizophrenia and varying duration of illness (0-3 years and >3 years). TF was defined differently across studies but included relapses due to psychiatric hospitalizations, arrest/incarceration, suicidal/homicidal ideation or behavior, discontinuation due to inadequate efficacy and/or safety/tolerability, treatment supplementation due to inadequate efficacy, or worsening of symptoms (based on PANSS or CGI-S). Treatment-emergent adverse events (TEAEs) were documented. Results: A total of 1269 patients were included (0-3 years: PP, n=302, OAP, n=326; >3 years: PP, n=325, OAP, n=316). Regardless of duration of illness, PP was associated with numerically fewer TFs versus OAP treatment, respectively (0-3 years: 17.9% vs 26.1%; >3 years: 32.3% vs 42.4%), as well as significant reductions in relative risk of TF (0-3 years: 34% [HR 0.66; 95% CI, 0.47-0.92, P=0.016] and >3 years: 31% [HR 0.69; 95% CI, 0.53-0.89, P=0.004]). TEAEs were reported in 77.0% of patients (0-3 years: PP, n=242 [80.1%], OAP, n=239 [73.3%]; >3 years: PP, n=254 [78.2%], OAP, n=242 [76.6%]). Conclusion: This patient-level meta-analysis suggests that treatment with PP provides significant benefit in reducing TF compared with OAP, regardless of duration of illness.Short Description: This patient-level meta-analysis was conducted to assess risk of treatment failure (TF) associated with paliperidone palmitate (PP) long-acting injectables (LAIs) versus oral antipsychotics (OAPs) in patients with varying duration of schizophrenia illness (0-3 years vs >3 years). Results suggest that PP LAIs provide significant benefit in reducing TF or relapse compared with OAPs, regardless of illness duration.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC