Abstract

Schizophrenia patients are generally treated with first (1G) or second-generation (2G) oral antipsychotics (OAP) or long-acting injectable (LAI) antipsychotics. There is no international consensus regarding optimal treatment sequence. This study modelled the cost-effectiveness of different treatment sequences of 1G and 2G LAI or OAP to identify optimal sequences for the maintenance treatment of schizophrenia in France based on real-world evidence. A semi-Markov cohort model with a 5-year time horizon and 3-month cycles was developed. Five health states are included in each line of treatment: stable treated, stable non-treated, relapse with and relapse without hospitalization and death. Clinically relevant combinations of 2G-LAI, 1G-LAI, 2G-OAP, 1G-OAP and clozapine (49 unique sequences, informed by expert opinion) were analysed across 4 lines of therapy. Clinical as well as resource use inputs for each drug class and health state utilities were sourced from European RWE studies. Acquisition cost for individual therapies were based on prices referenced on the French health insurance database. Clinical outcomes at 5-years were studied across the individual therapies. Cost-effectiveness outcomes were compared for all clinically relevant treatment sequences. Individually, 2G-LAI performed better than 2G-OAP in overall survival (95.98% for 2G-LAI vs. 93.92% for 2G-OAP), rehospitalisation rate (52.32% vs. 60.50%) as well as better adherence to the treatment (49.10% vs. 15.66%) over 5 years. From 49 treatment sequences, total costs ranged from €22,955 to €26,104 while cumulated QALYs ranged from 3.58 to 3.84. The analysis identified five optimal and cost-effective treatment combinations:1. 2G-OAP/1G-LAI/CLO/CLO2. 2G-OAP/1G-LAI/1G-LAI/CLO3. 2G-LAI/1G-LAI/2G-OAP/CLO4. 2G-LAI/2G-LAI/1G-LAI/CLO5. 2G-LAI/2G-LAI/2G-LAI/CLO Generally, sequences with first-line 2G-LAI showed greater clinical benefit such as reduced rehospitalisation (10% decrease between sequences 1. and 5.) and relapse (7 days decrease between the sequences 1. and 5.). These findings suggest 2G-LAI are a crucial component of cost-effective schizophrenia treatment, particularly at an early stage of disease.

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