OBJECTIVES: RBP-7000 (risperidone in ATRIGEL® delivery system) monthly subcutaneous LAI, demonstrated superior efficacy versus placebo in schizophrenia; however, direct comparisons to other LAIs are missing. We compared available data on second-generation LAIs via network meta-analysis (NMA) to assess differences in relevant efficacy and safety outcomes.

METHODS: EMBASE®, MEDLINE® and Cochrane databases were systematically searched until 02/2018 for randomized controlled trials (RCTs) in acutely exacerbated patients with schizophrenia. Bayesian NMA was conducted to evaluate mean change from baseline in total Positive and Negative Syndrome Scale (PANSS) and subscales. Extrapyramidal disorder, weight gain and discontinuations due to inefficacy (assumed remaining in relapse) were assessed and included: RBP-7000, paliperidone (PP1M), aripiprazole monohydrate (ARIP-MONO), aripiprazole lauroxil (ARIP-LAU) monthly intramuscular injections; Risperidone (RISP), Olanzapine (OLAN) bi-weekly intramuscular injections, and placebo as the reference. Data between 8-13 weeks were used in the analysis.

RESULTS: Eleven RCTs with sufficient similarity in baseline characteristics were identified and included in the analysis. After NMA adjustment, the change in PANSS Total score was generally similar without statistically significant or clinically meaningful differences between treatments (95% CI): RBP-7000 -8.33 (-13.08,-3.68), PP1M -7.62 (-10.33,-4.81), ARIP-MONO -15.09 (-20.57,-9.66), ARIP-LAU -11.53 (-15.90,-7.12), RISP -8.62 (-11.88,-5.51), OLAN -15.23 (-20.97,-9.33) versus placebo. Similar trend was seen in PANSS sub-scales. RBP-7000 also showed similar impact on weight gain and extrapyramidal disorder to all comparators (differences not significant). RBP-7000 had numerically lower inefficacy-related discontinuation versus the other LAI comparators, risk ratios versus placebo: RBP-7000 0.44 (0.05,1.18), PP1M 0.64 (0.48,0.81), ARIP-MONO 0.51 (0.27,0.87), ARIP-LAU 0.47 (0.23,0.8), RISP 0.73 (0.49,0.96), OLAN 0.58 (0.3,0.95); although the differences were not statistically significant.

CONCLUSIONS: Overall, RBP-7000 showed a positive safety profile. No significant differences in efficacy was observed between RBP-7000 and the other LAIs in indirect comparisons. Evaluation and potential adjustment for baseline characteristics differences across trials may improve robustness of these analyses.