F26. C-REACTIVE PROTEIN AND RESPONSE TO LURASIDONE TREATMENT IN ADOLESCENTS WITH SCHIZOPHRENIA

Abstract

Background: Cognitive impairment in schizophrenia has been associated with increased levels of inflammatory biomarkers including C-reactive protein (CRP). We investigated associations between CRP and change in cognitive performance measures during lurasidone treatment in adolescents with schizophrenia. Methods: Adolescent patients with schizophrenia (13-17 years old) were randomly assigned to 6 weeks of double-blind, fixed-dose lurasidone (40 or 80 mg/day) or placebo treatment. The primary efficacy measure was the change from baseline to week 6 in the Positive and Negative Symptom Scale (PANSS) total score. Cognitive function was assessed with the computerized CogState Brief Battery at baseline and week 6 endpoint. Ageand-sex-specific z-scores and percentiles in height and BMI at Baseline were obtained using WHO 2007 growth reference standards. Statistical interaction tests were applied to evaluate whether baseline hsCRP and BMI predicted differential response to lurasidone treatment (vs. placebo) on measures of symptom severity and cognitive function in adolescent subjects, with and without adjustment for age strata, gender, and study center. Results: There was a significant cross-sectional association between cognitive impairment and increased body weight level, adjusted for age, gender, and country. A significant hsCRP and BMI combined interaction effect was found for cognitive efficacy of lurasidone (vs. placebo) in adolescent subjects with schizophrenia (log hsCRP and lurasidone vs placebo interaction stratified by BMI, p < 0.05, adjusted for gender, age strata, and study center). Among overweight/obese patients, lurasidone (vs. placebo) showed greater cognitive response with increased level of CRP at study baseline. Among normal-weight patients, lurasidone (vs placebo) showed reduced cognitive response with increased level of CRP at study baseline. There were no significant moderating relationships between CRP, BMI and the efficacy of lurasidone (vs. placebo) for reducing psychotic symptom severity in adolescent patients with schizophrenia. Lurasidone treatment was not associated with significant change in hsCRP concentration at study endpoint. Discussion: In this post-hoc analysis utilizing data from a placebo-controlled study of adolescent patients with schizophrenia treated with lurasidone, our findings suggest improvement in cognitive performance can be associated with a combination of CRP and BMI at study baseline. Greater response to lurasidone treatment (vs. placebo) was observed in patients with lower systemic inflammation, and in overweight/obese patients with increased level of systemic inflammation at study baseline.