Earlier Use of Long-Acting Injectable Paliperidone Palmitate Once-Monthly versus Oral Antipsychotics in Patients with Schizophrenia: An Integrated Patient-Level Meta Analysis of the PROSIPAL and PRIDE Studies

Purpose: A previous integrated patient-level analysis demonstrated a significant benefit of implementing once-monthly injectable paliperidone palmitate (PP1M) earlier in the treatment course for schizophrenia. Earlier therapeutic interventions during the first 3-5 years after disease onset can positively impact long-term outcomes in schizophrenia. This present analysis evaluated the risk of relapse both overall and by different durations of illness (0-3 years, >3-5 years, and >5 years from diagnosis) in adult patients with schizophrenia who received PP1M or oral antipsychotics (OAPs). Patients and Methods: This analysis included integrated patient-level data from the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) and Prevention of Relapse with Oral Antipsychotics versus Injectable Paliperidone Palmitate (PROSIPAL) studies. Both studies assessed relapse as the primary outcome in patients treated either PP1M or OAPs. Results: Overall, the risk of relapse was reduced by 31% with PP1M compared to OAP (HR 0.69; 95% CI [0.56-0.86], P < 0.001). Fewer relapses were observed with PP1M versus OAP in the 0-3-year subgroup (15.8% and 21.7%, respectively), >3-5-year subgroup (19.6% and 29.9%, respectively), and >5-year subgroup (41.7% and 51.6%, respectively). These results represent a reduction in risk of relapse by 33% for patients receiving PP1M versus OAP in the 0-3-year subgroup (HR 0.67; 95% CI [0.44-1.00], P = 0.050), 43% in the >3-5-year subgroup (HR 0.57; 95% CI [0.35-0.93], P = 0.025), and 26% in the >5-year subgroup (HR 0.74; 95% CI [0.55-1.00], P = 0.049). Treatment-emergent adverse event rates were similar between treatment groups. Conclusion: This analysis indicates that PP1M provides significant benefits in reducing relapse rates compared to OAPs, regardless of the duration of illness. These findings emphasize the importance of initiating PP1M treatment early in the course of schizophrenia to achieve better long-term outcomes.