Comparative Efficacy, Safety, and Tolerability of KarXT Versus Aripiprazole and Cariprazine for the Acute Treatment of Adults With Schizophrenia: A Network Meta-Analysis


Hickey C1, Cajigal A2, Haycroft B3, Kramer K2, Sidovar MF2
1Lumanity, Bethesda, MD, USA, 2Karuna Therapeutics, Boston, MA, USA, 3Lumanity, Sheffield, UK

OBJECTIVES: To investigate the relative effectiveness, safety, and tolerability of xanomeline and trospium (KarXT) versus aripiprazole and cariprazine, for the acute treatment of schizophrenia.

METHODS: An evidence base for network meta-analysis (NMA) was pragmatically identified from the Huhn et al. 2019 systematic literature review and supplemented with additional aripiprazole and cariprazine studies identified from a PubMed search for randomized controlled trials (RCTs) published since 2019 and additional hand-identified records, including three RCTs investigating KarXT (EMERGENT-1, 2, and 3).

Bayesian random effects NMA models were fit for eight clinical, safety, and tolerability outcomes including clinical response (30% decrease in Positive and Negative Syndrome Scale [PANSS] total score), all-cause discontinuation, discontinuation due to adverse events, extrapyramidal symptoms, clinically significant weight gain (7% increase), and change from baseline PANSS scores (total score, positive symptoms score, and negative symptoms score). Five-week duration data from the EMERGENT trials were compared with 4–6 week data from comparator studies for each outcome.

Scenario analyses investigated the impact of using fixed effects NMA models and excluding studies which enrolled patient populations with substantially different race distribution.

RESULTS: 13 RCTs contributed to the network. Only trials which included relevant outcomes data were included in the NMA. Results suggest treatment with KarXT improved odds of clinical response versus aripiprazole (odds ratio [OR]: 1.97; 95% credible interval [CrI]: 1.11, 3.64) and cariprazine (OR: 2.09; 95% CrI: 1.17, 3.88), increased odds of all-cause discontinuation versus aripiprazole (OR: 1.91; 95% CrI: 1.22, 2.97), and reduced odds of clinically significant weight gain versus aripiprazole (OR: 0.21; 95% CrI: 0.08, 0.62) and cariprazine (OR: 0.19; 95% CrI: 0.06, 0.62),. Results from scenario analyses were largely consistent.

CONCLUSIONS: In this NMA, KarXT was found to have improved clinical response and reduced clinically significant weight gain compared with aripiprazole and cariprazine.

Conference/Value in Health Info

2024-05, ISPOR 2024, Atlanta, GA, USA

Value in Health, Volume 27, Issue 6, S1 (June 2024)




Clinical Outcomes, Economic Evaluation, Study Approaches

Topic Subcategory

Clinical Trials, Comparative Effectiveness or Efficacy, Cost-comparison, Effectiveness, Utility, Benefit Analysis, Meta-Analysis & Indirect Comparisons


Mental Health (including addition)

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