Comparative Efficacy, Safety, and Tolerability of Xanomeline and Trospium Chloride versus Eight Atypical Antipsychotics for the Acute Treatment of Adults with Schizophrenia - A Network Meta-Analysis
Author(s)
Conor Hickey, Msc1, Matthew Sidovar, MS2, Andrea Garcia, Msc1, Kenneth Kramer, PhD2, Amy Chang, Ms1, Katrin Kupas, PhD2, Vyshnavi Telukuntla, MS1, Andrew J. Cutler, MD3;
1Lumanity, Sheffield, United Kingdom, 2Bristol Myers Squibb, Princeton, NJ, USA, 3SUNY Upstate Medical University, Lakewood Ranch, FL, USA
1Lumanity, Sheffield, United Kingdom, 2Bristol Myers Squibb, Princeton, NJ, USA, 3SUNY Upstate Medical University, Lakewood Ranch, FL, USA
OBJECTIVES: To expand prior network meta-analyses investigating the relative efficacy, safety, and tolerability of xanomeline and trospium, for the acute treatment of schizophrenia.
METHODS: An updated systematic literature review (SLR) was undertaken, building on a 2019 SLR, to identify RCTs of eight oral antipsychotics for acute treatment of adults with schizophrenia. Our SLR identified new publications from January 1st 2019 to March 20th 2024 and re-evaluated previously identified records against new inclusion criteria. Bayesian NMAs were conducted for eleven outcomes: clinical response (≥30% decrease in Positive and Negative Syndrome Scale [PANSS] total score), all-cause discontinuation, discontinuation due to adverse events, sedation, somnolence, clinically significant weight gain (≥7% increase), change from baseline (CFB) PANSS scores (total, positive symptoms, and negative symptoms), CFB Clinical Global Impressions - Severity (CGI-S) score, and CFB weight.
RESULTS: Xanomeline/trospium treatment significantly improved odds of clinical response versus aripiprazole (odds ratio [OR]: 1.85; 95% credible interval [CrI]: 1.11, 3.11), brexipiprazole (OR: 2.23; 95% CrI: 1.34, 3.83), and cariprazine (OR: 2.05; 95% CrI: 1.19, 3.57), increased odds of all-cause discontinuation versus all comparators except cariprazine, and reduced odds of clinically significant weight gain versus aripiprazole, brexipiprazole, cariprazine, lumateperone, olanzapine, quetiapine, and risperidone. Further favorable results for xanomeline/trospium included improvements in: CFB CGI-S versus aripiprazole, brexpiprazole, cariprazine, and olanzapine, CFB PANSS positive symptoms score versus brexpiprazole, and CFB weight versus brexiprazole, clozapine, olanzapine, quetiapine, and risperidone.
CONCLUSIONS: Xanomeline/trospium demonstrated improved clinical response and reduced weight gain compared with several existing oral antipsychotics.
METHODS: An updated systematic literature review (SLR) was undertaken, building on a 2019 SLR, to identify RCTs of eight oral antipsychotics for acute treatment of adults with schizophrenia. Our SLR identified new publications from January 1st 2019 to March 20th 2024 and re-evaluated previously identified records against new inclusion criteria. Bayesian NMAs were conducted for eleven outcomes: clinical response (≥30% decrease in Positive and Negative Syndrome Scale [PANSS] total score), all-cause discontinuation, discontinuation due to adverse events, sedation, somnolence, clinically significant weight gain (≥7% increase), change from baseline (CFB) PANSS scores (total, positive symptoms, and negative symptoms), CFB Clinical Global Impressions - Severity (CGI-S) score, and CFB weight.
RESULTS: Xanomeline/trospium treatment significantly improved odds of clinical response versus aripiprazole (odds ratio [OR]: 1.85; 95% credible interval [CrI]: 1.11, 3.11), brexipiprazole (OR: 2.23; 95% CrI: 1.34, 3.83), and cariprazine (OR: 2.05; 95% CrI: 1.19, 3.57), increased odds of all-cause discontinuation versus all comparators except cariprazine, and reduced odds of clinically significant weight gain versus aripiprazole, brexipiprazole, cariprazine, lumateperone, olanzapine, quetiapine, and risperidone. Further favorable results for xanomeline/trospium included improvements in: CFB CGI-S versus aripiprazole, brexpiprazole, cariprazine, and olanzapine, CFB PANSS positive symptoms score versus brexpiprazole, and CFB weight versus brexiprazole, clozapine, olanzapine, quetiapine, and risperidone.
CONCLUSIONS: Xanomeline/trospium demonstrated improved clinical response and reduced weight gain compared with several existing oral antipsychotics.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO95
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Mental Health (including addition), SDC: Neurological Disorders