Objective: To determine whether reductions in psychiatric hospitalizations with early initiation of paliperidone palmitate (PP) versus oral antipsychotic (OAP) therapy observed in a DREaM post hoc analysis are reproducible in real-world patients with recent-onset schizophrenia.

Methods: US patients diagnosed with schizophrenia and enrolled in the DREaM RCT received treatment with continuous OAP for 18 months (OAP-OAP cohort, n=45), continuous PP for 18 months (PP-PP cohort, n=44), or OAP for 9 months then PP for 9 months (OAP-PP cohort, n=43). DREaM inclusion/exclusion criteria were used to identify a real-world OAP-OAP treated cohort using 2015-2019 Truven IBM Medicaid Managed Care databases (MMC, n=1000). MMC and DREaM cohorts were combined, and the propensity score of belonging to the MMC cohort was estimated using baseline variables identified from double-lasso regression. Weighted DREaM OAP-OAP psychiatric hospitalizations were compared with observed MMC psychiatric hospitalizations for calibration. Weighted DREaM OAP-PP and PP-PP psychiatric hospitalizations were compared with observed MMC psychiatric hospitalizations for real-world effectiveness estimates.

Results: Standardized mean differences in baseline covariates between DREaM and MMC cohorts were substantially reduced (<0.5) after calibration. The 18-month cumulative numbers of psychiatric hospitalizations per patient were 0.83 (SE, 0.14) in the MMC cohort, 0.43 (0.14) in the unweighted DREaM OAP-OAP cohort, and 0.79 (0.37) in the calibrated DREaM OAP-OAP cohort. The latter was not statistically different from the MMC cohort (difference=0.035 [95% CI: –0.67, 0.81]), implying similarities for patients between the MMC and calibrated DREaM cohorts. Calibrated effects on 18-month cumulative psychiatric hospitalizations for OAP-PP and PP-PP in comparison with observed MMC outcomes were –0.77 (95% CI: –1.08, –0.47) and –0.83 (95% CI: –1.15, –0.60), respectively.

Conclusion: DREaM data could be successfully calibrated to MMC. Calibration results showed that early initiation of PP may reduce psychiatric hospitalizations in real-world patients, with magnitudes larger than those observed in the DREaM RCT.