Long-Term Real-World Effectiveness of Aripiprazole Once-Monthly. Treatment Persistence and Its Correlates in the Italian and Spanish Clinical Practice: A Pooled Analysis

Abstract

BackgroundOne of the most significant risk factors for relapse and hospitalization in schizophrenia is non-adherence to antipsychotic medications, very common in patients with schizophrenia. The aim of this analysis was to evaluate the treatment persistence to aripiprazole once-monthly (AOM) and the factors affecting it in the pooled population of two similar studies performed previously in two different European countries.MethodsPooled analysis of two non-interventional, retrospective, patient record-based studies: DOMINO and PROSIGO. Both analyzed treatment persistence after starting AOM treatment in the real-world setting. The primary variable was persistence with AOM treatment during the first 6 months after treatment initiation. A multivariate Cox regression model was used to evaluate the influence of several baseline characteristics on the persistence.ResultsThe study population comprised 352 patients included in the two studies, DOMINO (n = 261) and PROSIGO (n = 91). The overall persistence with AOM treatment at the end of the 6-month observation period was 82.4%. The multivariate analysis showed that patients with “secondary school” level of education present a 67.4% lower risk of discontinuation within 6 months after AOM initiation when compared with “no/compulsory education patients” (p = 0.024). In addition, patients with an occupation present a 62.7% lower risk of discontinuation when compared with unemployed patients (p = 0.023). Regarding clinical history, patients with a Clinical Global Impression—Severity scale (CGI-S) score ≤3 present a 78.1% lower risk of discontinuation when compared with patients with a CGI-S score ≥6 (p = 0.044), while patients with a time since schizophrenia diagnosis ≤8.4 years present a 52.9% lower risk of discontinuation when compared with the rest of patients (p = 0.039).ConclusionThe AOM persistence rate observed in this study was 82.4%, which was higher than that reported in clinical trials, aligned with other real-life studies and higher than reported for other long-acting injectable antipsychotics. The persistence rate was high in complex patients, although patients with higher level of education, active occupation, lower initial CGI-S score and shorter time since the diagnosis of schizophrenia appear to be more likely to remain persistent with AOM during the 6 months after initiation.

Clinical Experience on the Use of a Single-day, Two-injection Start Initiation Regimen of Aripiprazole Once Monthly in Patients With Schizophrenia in Spain: SaTISfy Study

“…Low adherence to treatment was leading to hospitalizations and was consequently one of the reasons psychiatrists gave for choosing AOM400 over other antipsychotics. Previous studies have shown a high persistence of AOM400, as around 80% of patients continued their treatment after 6 months of treatment 28–30 . According to these studies, the persistence rate (71.4% to 86% in a 6-month period) varied based on the baseline characteristics of patients, being higher for those with fewer symptoms and a shorter time since diagnosis, highlighting the importance of early treatment with AOM400.…”

“…In addition, they appeared during the first weeks of treatment and tended to stabilize over time without significant differences when compared with a placebo 33,34 . In contrast, these AEs were rare in real-world studies, affecting fewer than 1.5% of patients and leading to only a small number of discontinuations 28,35 . Surprisingly, in a study published by Schottle et al 35 in 2018, the most common treatment-related AE was the fact that the medication was taken at an inappropriate time in 24.8% of patients, which in most cases involved oral aripiprazole being discontinued earlier than recommended (< 2 wk of the recommended concomitant treatment after the first injection).…”

“…Previous studies have shown a high persistence of AOM400, as around 80% of patients continued their treatment after 6 months of treatment. [28][29][30] According to these studies, the persistence rate (71.4% to 86% in a 6-month period) varied based on the baseline characteristics of patients, being higher for those with fewer symptoms and a shorter time since diagnosis, highlighting the importance of early treatment with AOM400. It is noteworthy that lack of adherence to previous treatment was the main reason for initiating AOM400-TIS according to some psychiatrists in our study, pointing to the importance of an initiation regimen involving only 1 oral dose as a potential factor in improving adherence during the first weeks of treatment.…”

“…33,34 In contrast, these AEs were rare in real-world studies, affecting fewer than 1.5% of patients and leading to only a small number of discontinuations. 28,35 Surprisingly, in a study published by Schottle et al 35 in 2018, the most common treatment-related AE was the fact that the medication was taken at an inappropriate time in 24.8% of patients, which in most cases involved oral aripiprazole being discontinued earlier Mean hospitalization time (in days) of patients in acute psychiatry units in Spain, 17 of patients with schizophrenia according to the psychiatrists in the study independently of their treatment, and of patients treated with AOM400-TIS. The error bars represent the SD.…”

Aripiprazole once monthly as a maintenance treatment for patients with schizophrenia and alcohol/substance use disorder: an observational, real-world study

“…Several factors must be taken into account, including not only the severity of the psychiatric symptomatology but also of the substance-related disorder, the age of the patients, the living conditions and the type of treatment, all of which cannot be investigated from the data available. Recently, Olivares and Fagiolini (2022) analysed factors of treatment persistence with aripiprazole once monthly in the Italian and Spanish clinical practice, finding that patients with a secondary school level of education and with an occupation, respectively, presented a 67.4% and 62.7 lower risk of discontinuation within six months after aripiprazole once monthly initiation; moreover, they found that patients with a CGI score ≤ 3 presented a 78.1% lower risk of discontinuation if compared with patients with a CGI score ≥ 6, whereas patients with a time since schizophrenia diagnosis ≤ 8.4 years presented a 52.9% lower risk of discontinuation if compared with the others (Olivares and Fagiolini, 2022). Previously, several studies had recorded that the percentage of SUD patients who discontinued a psychiatric treatment ranged from 33.7% in a sample of 199 Japanese sample of inpatients and outpatients at a public psychiatric hospital (Masaki and Toyomasu, 2010) to 34.8% in a Spanish sample of 264 patients on treatment in psychiatric clinical centres in Girona (Calvo et al , 2018) and to 36% in an American outpatient sample enrolled in an addiction programme (King and Canada, 2004).…”