Paliperidone Palmitate 3-month Research Articles

Long term impact of 3-monthly paliperidone palmitate on hospitalisation in patients with schizophrenia: Six-year mirror image study.

Long term impact of 3-monthly paliperidone palmitate on hospitalisation in patients with schizophrenia: Six-year mirror image study.

Relapse Rates With Paliperidone Palmitate in Adult Patients With Schizophrenia: Results for the 6-Month Formulation From an Open-label Extension Study Compared to Real-World Data for the 1-Month and 3-Month Formulations.

The 3 paliperidone palmitate (PP) long-acting injectable antipsychotic formulations, PP 1-month (PP1M), PP 3-month (PP3M), and PP 6-month (PP6M), have shown to reduce the risk of relapse in schizophrenia. The current phase-4 study constructed external comparator arms (ECAs) using real-world data for PP3M and PP1M and compared relapse prevention rates with PP6M from an open-label extension (OLE) study in adult patients with schizophrenia. PP6M data were derived from a single-arm, 24-month, OLE study (NCT04072575), which included patients with schizophrenia who completed a 12-month randomized, double-blind, noninferiority, phase-3 study (NCT03345342) without relapse. Patients in the PP3M and PP1M ECAs were identified from the IBM® MarketScan® Multistate Medicaid Database based on similar eligibility criteria as the PP6M cohort. A total of 178 patients were included in each cohort following propensity score matching. Most patients were men (>70%; mean age: 39-41 years). Time to relapse (primary analysis based on Kaplan-Meier estimates) was significantly delayed in the PP6M cohort (P<.001, log-rank test). The relapse rate was lower in the PP6M cohort (3.9%) vs PP3M (20.2%) and PP1M (29.8%) cohorts. Risk of relapse decreased significantly (P<.001) by 82% for PP6M vs PP3M (HR = 0.18 [95% CI = 0.08 to 0.40]), 89% for PP6M vs PP1M (HR = 0.11 [0.05 to 0.25]), and 35% for PP3M vs PP1M (HR = 0.65 [0.42 to 0.99]; P = .043). Sensitivity analysis confirmed findings from the primary analysis. Although the ECAs were matched to mimic the characteristics of the PP6M cohort, heterogeneity between the groups could exist due to factors including prior study participation, unmeasured confounders, variations in data capture and quality, and completeness of clinical information. In a clinical trial setting, PP6M significantly delayed time to relapse and demonstrated lower relapse rates compared with PP3M and PP1M treatments in real-world settings among adult patients with schizophrenia. ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.

Cumulative Clinical Experience of the Use of Paliperidone Palmitate 3-Monthly Long-Acting Injection in the Treatment of Schizophrenia: A Critical Appraisal.

Paliperidone palmitate 3-monthly (PP3M), an approved maintenance treatment for patients with schizophrenia, was the first long-acting antipsychotic injectable (LAI) to require only four administrations per year. Here, we aimed to review the available evidence about its use in the management of schizophrenia to date and highlight key study findings in order to provide a balanced overview of current experience in clinical practice. For that purpose, an extensive search of available literature from PubMed, Embase, and Web of Science was conducted in March 2023. Emerging data from real-world studies appear to signal that the benefits of the use of PP3M may well extent beyond the obvious convenience for patients and resource efficiency for services and may be actually associated with improved effectiveness and patient satisfaction. Large naturalistic studies from Australia, Europe and the US comparing treatment continuation between newer LAIs and/or oral antipsychotics showed that patients treated with PP3M had higher compliance rates and a longer period of continuous use. The risk of relapse, re-hospitalization and number of bed days was also lower with PP3M compared to PP1M and other LAIs as demonstrated by several cohort studies. Furthermore, patients treated with PP3M were using lower doses of benzodiazepines and concomitant oral antipsychotics compared with other LAIs. What is more, PP3M appears to positively impact patients' satisfaction and quality of life, facilitating long-term goals. In fact, recent studies recorded better quality-adjusted life years and decreased stigma, with improved social acceptability and promotion of rehabilitation for patients transitioning to PP3M. The rates of general satisfaction rates with PP3M were also higher among psychiatrists and caregivers who reported overall less concerns. In conclusion, clinical exposure and a growing body of evidence thus far, reinforce the use of PP3M in an effort to enhance patient outcomes alongside individual experience and treatment persistence.

Treatment Retention Rates of 3-monthly Paliperidone Palmitate and Risk Factors Associated with Discontinuation: A Population-based Cohort Study.

Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration > 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180-360 days (adjusted relative risk [aRR], 1.76) or < 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

Long-term Efficacy and Safety of Paliperidone 6-month Formulation: An Open-label 2-year Extension of a 1-year Double-blind Study in Adult Participants With Schizophrenia.

Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month (PP3M) in preventing relapse in patients with schizophrenia in a phase-3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study. Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal-injections (700/1000mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale (PANSS) total score, Personal and Social Performance (PSP) score, and Clinical Global Impression-Severity (CGI-S) scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests. Of 178 participants enrolled, 154 (86.5%) completed the OLE; mean age: 40.4 years, men: 70.8%. Mean duration of PP6M exposure during OLE was 682.1 days. Overall, 7/178 (3.9%) participants relapsed between 20-703 days after enrolment. Mean (SD) change from baseline to endpoint: PANSS total score, 0.7 (8.22); CGI-S, 0.0 (0.51); PSP Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headaches (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs; no deaths were reported. The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE and no new safety concerns were identified.

Switching from Monthly to Three-Monthly Long-Acting Injectable Paliperidone: A Survey on Subjective Satisfaction and Safety.

Poor adherence to antipsychotic medication is common in the treatment of schizophrenia and other psychotic disorders. Paliperidone palmitate 3-monthly (PP3M) is the first long-acting injectable (LAI) antipsychotic to allow for only four medication administrations per year, and although there is sufficient information available about the clinical effects, there is relatively limited insight into the subjective experience of people with lived experience. This descriptive, cross-sectional survey explored patient's satisfaction and perspectives on the advantages and disadvantages of switching from monthly to 3-monthly paliperidone while also reporting on perceived levels of safety with regard to the reducing dose regimen during the Covid-19 pandemic. Information on discontinuation and hospitalisation rates at one year was also collected from the electronic records. Of the 46 patients included in the study, the vast majority reported feeling satisfied (89.2%) and safer (93.5%) after switching to the three-monthly formulation. Participants highlighted several advantages of changing to PP3M, most notably convenience (93.5%), improved quality of life (58.7%), decreased stigma (39.1%) and better adherence (28.3%). Furthermore, 93.5% of respondents experienced no disadvantages, while 6.5% described worsening side effects or symptoms. In fact, only one patient discontinued PP3M at one year with the overall number of hospitalisations also reducing in the same period compared to the year before switching. Our findings add to the small, but growing, body of evidence supporting patient satisfaction and acceptance with the use of PP3M and may reinforce the use of less frequent LAIs in clinical practice to enhance individual experience and treatment persistence and decrease levels of stigmatisation.

Analyzing Demographic Variabilities Associated With Age of Diagnosis of Schizophrenia Among Patients in Controlled Clinical Trials

AbstractBackgroundPrior literature and epidemiological data suggests that the age of diagnosis of schizophrenia (AOD) follows a bimodal and trimodal distribution for males and females, respectively. The studies used to generate these findings were often small and relied on self-reported patient data from a single geographic region in addition to other methodological limitations. We replicated these studies using a modern big data approach by combining raw data from large randomized controlled clinical trials.MethodsPatient-level data from 15 similarly designed, randomized, double-blind, placebo-controlled, crossover studies with patients using paliperidone extended-release tablets, paliperidone palmitate 1-month, and paliperidone palmitate 3-month, were obtained through the Yale Open Data Access Initiative (YODA). Descriptive statistics and histograms were calculated for continuous variables. A multivariable linear regression was performed with AOD as the outcome variable. Race and sex were used as predictor variables.ResultsOur final analysis included 7881 patients consisting of male (n=4962) and female (n=2919) patients among different racial demographics. Race was consolidated into the following groups: Asian (n=949), Black (n=1692), Hispanic (n=3), Southeast Asian (n=17), White (n=4769), and other (n=343) based on patient self-identification on the YODA datasets. A chi-square test revealed that there is a statistically significant association between patient sex and AOD (x2=295.61, df=68, p &lt; 0.0001). By proxy, this likely means that sex affects age of onset (AOS) as well. Our linear regression output with sex as a predictor of AOD revealed that only the male variable was found to have a statistically significant relationship (p&lt;0.0001) with AOD and resulted in a lower AOD. Histograms generated with the frequency of occurrences against AOD for both male and female patients appeared to be unimodally distributed and skewed right. However, the AOD for female and male patients were found to be 28.79 and 25.44 years old, respectively. This demonstrates that while both male and female AOD are distributed unimodally, there are slight differences in their distributions.ConclusionOur analysis differs from previous studies and finds that AOD for male and female patients are seen in a unimodal distribution as compared to previous literature that shows a bimodal and trimodal distribution. Our findings not only call for a re-evaluation of previous epidemiological understandings of AOD but may support future efforts in understanding the origins and typical clinical presentations of patients with newly developed symptomatology of schizophrenia as well as support clinicians’ perspectives as part of clarifying differential diagnoses. Further studies can also continue to evaluate possible correlations among different races.FundingNo Funding

Efficacy and Safety of Paliperidone Palmitate 6-Month versus Paliperidone Palmitate 3-Month Long-Acting Injectable in European Patients with Schizophrenia: A Post Hoc Analysis of a Global Phase-3 Double-Blind Randomized Non-Inferiority Study.

To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M). This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan-Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as -10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated. A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of -4.9% (95% CI: -9.2%, -0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs. The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified.

Efficacy of paliperidone palmitate 3-month formulation in preventing hospital admissions and emergency room visits. 66 months of follow-up

IntroductionPaliperidone Palmitate 3-month formulation (PP3M) has shown a significantly longer time to relapse compared to placebo, with similar efficacy and safety to Paliperidone Palmitate 1-month (PP1M) (Carpiniello et al. Drug Des. Devel. Ther. 2016; 10 1731–1742).ObjectivesThe main objective of this study was to determine the effectiveness of PP3M in preventing hospital admissions and emergency room visits, in people with non-acute schizophrenia in a naturalistic psychiatric outpatient settingMethodsSample: 30 people with diagnosis of schizophrenia (DSM 5 criteria), who had started treatment with PP3M, after being stabilized with PP1M (the dose was not modified in the four months prior to inclusion in the study)Quarterly basis, the following evaluations were performed during a follow-up period of 66 months:The Clinical Global Impression-Schizophrenia scale (CGI-SCH)Treatment adherence, concomitant medication and the number of hospitalizations and emergency visitsEfficacy values: Percentage of patients who remained free of admissions at the end of 66 months of follow-up.Other evaluation criteria: Percentage of patients who never visited the emergency department at the end of 66 months of follow-up. Average change from baseline visit to the final evaluation as assessed by score obtained on the following scale: GSI-SCH, percentage of patients on antipsychotic monotherapy and treatment adherence rate.ResultsThe mean dose of PP3M was 401. 55 mgThe percentage of patients who remained free of admissions at the end of the 66 months was 83.25% and the percentage of patients who never visited the emergency department at the end of 66 months was 79.92%Mean variations from baseline scores at 66 months were: (-0.36 ±0-37) on the GCI-SCH.The percentage of patients on antipsychotic monotherapy at the end of the 66 months was 76.56%The rate of adherence was 86.58%.ConclusionsIn our study, we found that paliperidone palmitate 3-month formulation was effective in reducing the number of admissions and visits to the emergency department, under conditions of daily clinical practice.Disclosure of InterestNone Declared

Alternative initiations with 6-monthly paliperidone palmitate. A retrospective study

Introduction6-monthly paliperidone palmitate features an initiation regimen through 1-monthly paliperidone palmitate or 3-monthly paliperidone palmitate. Some patients do not have sufficient adherence to treatment and it is necessary at the clinical level to start directly with 6-monthly paliperidone palmitate. There is little clinical experience with these alternative initiations and through this work those that have been carried out for 12 months at the Hospital Universitario Infanta Elena are exposed.ObjectivesThe main objective of the study is to describe the alternative initiations performed with 6-monthly paliperidone palmitate in routine clinical practice, having opted for a regimen different from the standard for clinical reasons.MethodsA retrospective selection of patients will be made through non-probabilistic consecutive sampling, including all patients who have been administered 6-monthly paliperidone palmitate with a start different from the standard during the last 4 months. To do this, the electronic medical record will be used, first selecting the patients who have started 6-monthly paliperidone palmitate through the anonymized digital records and, later, including in the study only those who have followed an alternative initiation pattern. The variables studied will be the following: age, sex, diagnosis, dose of paliperidone palmitate, initiation regimen, consumption of toxic substances, absenteeism from 6-monthly paliperidone palmitate, and visits to the emergency room and admissions.ResultsThe study included a total of 20 patients (n: 20). 80% of the patients were male and 20% were female. The mean age was 39.7 years. 75% of the patients had an associated substance use disorder. The following alternate starting schedules were performed with biannual paliperidone palmitate: monthly paliperidone palmitate on days 1 and 8, and 6-monthly paliperidone palmitate on day 38 (n: 11); monthly paliperidone palmitate 150 mg together with semi-annual paliperidone palmitate both on day 1 (n: 5); biannual paliperidone palmitate on day 1 supplemented with oral paliperidone for 45 days (n:4). A total of 0 visits to the emergency department and 0 admissions were observed after the 6-monthly paliperidone palmitate regimen.ConclusionsAlternative initiations with 6-monthly paliperidone palmitate may be a useful and safe clinical alternative in patients with very low adherence who, due to clinical needs, require starting 6-monthly paliperidone palmitate earlier in order to guarantee adherence.Disclosure of InterestNone Declared

Clinical experiences with 6-monthly paliperidone palmitate after 12 months of use. A retrospective study

IntroductionLong-acting injectable antipsychotics (LAIA) have provided a significant improvement in the treatment of schizophrenia. Although there is already significant clinical experience with paliperidone palmitate, it is important to evaluate the clinical response of patients to this new 6-monthly presentation, so descriptive studies based on real clinical evidence can be very useful for this purpose.ObjectivesThe main objective of the study is to describe the use of 6-monthly paliperidone palmitate in routine clinical practice, providing variables that objectify the evolution such as the number of admissions and visits to the emergency room.MethodsRetrospective descriptive study with a sample selected by non-probabilistic consecutive sampling, retrospective type, in a time interval of 12 months (n=40). The patients selected were all those who received 6-monthly paliperidone palmitate treatment, with a diagnosis of schizophrenia, in 12 months of use at Hospital Universitario Infanta Elena. A descriptive analysis was performed. Mean and standard deviation were calculated for quantitative variables and N and percentage for categorical variables.ResultsA total of 40 administrations of 6-monthly paliperidone palmitate were performed in the study. None of the patients presented adverse reactions related to the administration of the drug, not reporting local pain or inflammation of the puncture area, except for the characteristic discomfort of an intramuscular puncture. Regarding the efficacy of 6-monthly paliperidone palmitate, none of the patients presented a psychotic decompensation after its administration, maintaining psychopathological stability after the change. The switch to 6-monthly paliperidone palmitate was made from both 1-monthly paliperidone palmitate and 3-monthly paliperidone palmitate, both showing the same efficacy. Regarding tolerability, all the patients who were administered 6-monthly paliperidone palmitate were previously treated with the monthly and quarterly presentation of the same molecule, having presented good tolerability to it, maintaining said tolerability after treatment. change to 6-monthly paliperidone palmitate, with no adverse reaction being recorded after the change. The adherence presented by the patients was very good, performing 100% of the administrations of 6-monthly paliperidone palmitateConclusions6-monthly paliperidone palmitate may be an effective and well-tolerated treatment for the treatment of schizophrenia. In the present study, the use of said LAIA in a group of 40 patients is objectified, showing excellent efficacy and tolerability. All study patients were already stable with the 1-monthly and 3-monthly paliperidone palmitate formulations, maintaining said psychopathological stability when switching to the 6-monthly paliperidone palmitate formulation, with excellent adherence and adverse effect profile .Disclosure of InterestNone Declared

Alternative initiations with 6-monthly paliperidone palmitate. A descriptive study

Introduction 6-monthly paliperidone palmitate features an initiation regimen through 1-monthly paliperidone palmitate or 3-monthly paliperidone palmitate. Some patients don´t have sufficient adherence to treatment and it is necessary at the clinical level to start directly with 6-monthly paliperidone palmitte. There is une little clinical experience with these alternative initiations and throuht this work those that have been carried out for 12 months at the Rey Juan Carlos Hospital are exposed. Objectives The main objective of the study is to describe the alternative initations performed with 6-monthly paliperidone palmitate in routine clinical practice, having opted for a regimen different from the standard for clinical reasons. Methods A retrospective selection of patiens will be made throuht non-probabilistic consecutive sampling, including all patients who have benn administered 6-monthly paliperidone palmitate with a stard different form the standard during the last 6 months. To do his, the electronic medical record will be used, first selecting the patients who have started 6-monthly paliperidone palmitate through the anonymized digital records and, later, including in the study only those who have followed and alternative initiation pattern. The variables studied will be the following: age, sex, diagnosis, dose of paliperidone palmitate, initiation regimen, consumption of toxic substances, absenteeism from 6-monthly paliperidone palmitate, visits to the emergency room and admissions. Results The study included a total of 5 patients ( n:5). 80% of the patients were male and 20%were female. The mean age was 39.7 years. 80% of the patients had an associated substance use disorder. The following alternate sarting schedules were with biannual paliperidone palmitate: monthly paliperidone palmitate 150 mg together with semi-annual paliperidone palmitate both on day 1 ( n: 2) or monthly paliperidone palmitate 150 mg on day 1, monthly paliperidone palmitate 100 mg on day 5 and semi-annual paliperidone palmitate on day 12 ( n: 3 ). A total of 0 visits to the emergency department and 0 admissions were observed after the 6-monthly paliperidone palmitate regimen. Conclusions Alternative initations with 6-monthly paliperidone palmitate may be a useful and safe clinical alternative in patients with very low adherence who, due to clinical needs, require startin 6-monthly paliperidone palmitate earlier in order to guarantee adherence . Disclosure of Interest None Declared

Long-term efficacy and safety of paliperidone 6-month formulation: An open-label extension of a double-blind study in adult patients with schizophrenia

IntroductionPaliperidone palmitate 6-month (PP6M), administered twice-yearly, demonstrated non-inferiority to paliperidone palmitate 3-month (PP3M) in preventing relapse in patients with schizophrenia in a phase-3 randomized, double-blind (DB) global study.1 We report results of a 2-year single-arm, open-label extension (OLE) of this study (NCT04072575).ObjectivesTo assess long-term efficacy and safety of PP6M in patients with schizophrenia.MethodsPatients who completed DB study without relapse were enrolled and followed up every 3 months for up to 2 years. Patients received 4 PP6M injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included relapse rate, Positive and Negative Syndrome Scale (PANSS) total score, Personal and Social Performance (PSP) score, and Clinical Global Impression-Severity (CGI-S) scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations and laboratory tests.ResultsOf 178 patients, 154 (86.5%) completed the study; mean age: 40.4 years; 70.8% were men. Mean duration of PP6M exposure was 682.1 days. Overall, 7/178 (3.9%) patients relapsed between 20 to 703 days after enrolment. Mean (SD) change from baseline to endpoint: PANSS total score, 0.7 (8.22); CGI-S, 0.0 (0.51); PSP Scale, 0.5 (7.47). Overall, 111/178 patients (62.4%) reported ≥1 TEAE; most common (&gt;10%) TEAEs were headache (13.5%) and blood prolactin increased (10.7%). Total, 7/24 patients withdrew due to TEAEs, and 8/178 (4.5%) patients experienced serious TEAEs; no deaths were reported.ConclusionsRelapse rate with PP6M was very low (&lt;4%). Clinical improvements in PANSS, CGI-S, and PSP scales demonstrated in DB study were maintained during this 2-year OLE study and no new safety concerns were identified.Reference1. D. Najarian et al. Int J Neuropsychopharmacol. 2022 Mar 17;25(3):238-251.Disclosure of InterestD. Najarian Shareolder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, I. Turkoz Shareolder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, S. Galderisi Consultant of: Janssen, Gedeon Richter-Recordati, Angelini, Speakers bureau of: Angelini, Gedeon Richter-Recordati, Janssen, Lundbeck, Sunovion, Recordati, H. Lamaison Grant / Research support from: Novartis, Eli Lilly, Lundbeck, Servier, AstraZeneca, Wyeth, Pfizer, Otsuka, Takeda, Sunovion, Roche, Janssen Pharmaceutical, Speakers bureau of: Servier, Abbot, Raymonds, Raffo, Temis Lostalo and Janssen Pharmaceutical, P. Zalitacz: None Declared, S. Aravind Shareolder of: Johnson &amp; Johnson, Employee of: Advarra, Inc. USA, U. Richarz Shareolder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development-Cilag, Switzerland.

Effects of Long-acting Injectable 3-Monthly Paliperidone Palmitate on the Clinical and Social Performance of Patients with Schizophrenia

To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p < 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71-100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p < 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p < 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p < 0.001; McNemar-Bowker test). Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.

Comparative effectiveness study of paliperidone palmitate 6-month with a real-world external comparator arm of paliperidone palmitate 1-month or 3-month in patients with schizophrenia.

The paliperidone palmitate 6-month (PP6M) long-acting injectable formulation is currently the longest dosing interval available for schizophrenia treatment. To compare treatment outcomes between a real-world external comparator arm (ECA; NeuroBlu database) and the PP6M open-label extension (OLE) clinical trial arm. The ECA comprised patients receiving PP 1-month (PP1M) or PP 3-month (PP3M) for ⩾12 months without a relapse. The PP6M OLE arm included patients with PP1M treatment prior to randomization who completed the 12-month double-blind PP6M study on either PP3M or PP6M relapse-free. Inverse probability treatment weighting (IPTW) was used to study time-to-relapse (primary outcome) and change in Clinical Global Impressions-Severity (CGI-S) score (secondary outcome). At 24 months, 3.9% (7/178) of patients in the PP6M cohort experienced a relapse versus 15.6% (26/167) in the ECA. Time-to-relapse was longer in the PP6M cohort versus the ECA at 12-, 18-, and 24-months across the different weighting methods; median time-to-relapse was not reached in both cohorts. Hazard ratio (HR) for relapse was significantly lower for the PP6M cohort versus the ECA throughout the duration of the study [HR at 24 months: 0.18 (95% CI: 0.08-0.42), p < 0.001]. At 24 months, change in CGI-S score for the PP6M cohort was 0.76 points lower than the ECA (p < 0.001). Results were similar in a sensitivity analysis using propensity score matching (PSM); IPTW resulted in larger sample sizes in balanced dataset than PSM. Consistent findings across weighting and matching methods suggest PP6M efficacy in reducing and delaying relapses and long-term symptom control compared to PP1M/PP3M in usual-care settings. Additional confounds, such as greater illness severity and more frequent comorbidities and comedications in the ECA, were not fully controlled by the applied statistical methods. Future real-world studies directly comparing PP6M with PP3M/PP1M and adjusting for these confounders are warranted.

Persistence and adherence to second-generation antipsychotic long-acting injectable medications for schizophrenia: A comparative study in the Australian context

To examine patient characteristics, persistence and adherence to treatment associated with use of second-generation antipsychotic long-acting injectable (SGA LAI) medications in the Australian real-world setting. Five SGA LAIs were compared using a retrospective 10% sample of prescriptions in Australian Pharmaceutical Benefits Scheme (PBS) data: paliperidone palmitate 1-monthly (PP1M), paliperidone palmitate 3-monthly (PP3M), aripiprazole monohydrate (ARI), risperidone (RLAI) and olanzapine pamoate (OLAI). Patients in the PP3M cohort were more persistent with treatment (p < 0.001). Median months of persistence: PP3M (36months); ARI (18months); PP1M (11months); OLAI (8months); RLAI (4months). Patients in the PP3M cohort were more adherent to treatment (p < 0.001): PP3M (78%); ARI (51%); PP1M (46%); OLAI (35%); RLAI (33%). Patients on PP3M treatment showed comparatively longer persistence and better adherence. Treatments for schizophrenia with longer dosing intervals may provide patients with symptomatic stability that could allow for reduced hospitalisations/relapse and increased focus on functional recovery.

Results from PSIPROSPER: A multicenter retrospective study to analyze the impact of treatment with paliperidone palmitate 1-month on clinical outcomes and hospital resource utilization in adult patients with schizophrenia in Portugal.

Schizophrenia is a chronic psychiatric disorder with a significant impact worldwide. The early onset and its relapsing nature pose a significant challenge to patients and caregivers. The PSIPROSPER study aimed to characterize the real-world context of schizophrenia treatment in Portugal and to measure the impact of including paliperidone palmitate 1-month formulation (PP1M) in the clinical outcomes (relapses and hospitalizations) and healthcare resource utilization, in a context in which payment scheme in Portugal allows for patients to receive free antipsychotics if prescribed at public hospitals. This was a multicenter, retrospective, observational study. Male and female adults with a diagnosis of schizophrenia who initiated treatment with PP1M after a minimum of 12 months on an Oral Antipsychotic (OAP), and with complete medical charts, were consecutively included. A mirror-image design over 24 months allowed the comparison of outcomes before and after the PP1M introduction. Out of the 51 patients included, 80.4% were male, with a mean age of 34 (±9.8) years. Around 92% of patients were being treated with PP1M at inclusion. Lack of adherence to previous OAP was the main driver for PP1M initiation. Only 9.8% of patients were hospitalized during the PP1M period vs. 64.7% during the OAP period (p < 0.0001). The mean number of hospitalizations (0.1) was significantly lower during the PP1M period (p < 0.0001). Type of treatment was the only variable found to be significant in predicting a lower hospitalization rate and a lower risk of hospitalization. Relapses were significantly lower (p < 0.0001) in PP1M (21.6%) vs. OAP (83.7%). Similarly, the mean change in the number of relapses (p < 0.0001) showed significantly better outcomes in PP1M. This study supports PP1M as part of schizophrenia treatment in Portugal. Given the lower number of relapses and hospitalizations observed in schizophrenia patients treated with PP1M when compared to OAP-treated patients, this real-world study seems to provide further evidence to support the use of PP1M to treat this condition, in line with previous research. In the context of scarce public resources, these benefits should be carefully considered by healthcare decision-makers to ensure optimal value-based treatment strategies.

Efficacy of paliperidone palmitate 3-month formulation in preventing hospital admissions. 60 months of follow-up

IntroductionPaliperidone Palmitate 3-month formulation (PP3M) has shown a significantly longer time to relapse compared to placebo, with similar efficacy and safety to Paliperidone Palmitate 1-month (PP1M). However, studies of longer duration are required.ObjectivesThe main objective of this study is to determine the effectiveness of PP3M in the prevention of hospitalizations in patients with non-acute schizophrenia in a naturalistic outpatient psychiatric setting.MethodsSample: 30 patients diagnosed with schizophrenia (DSM 5) that started treatment with PP3M after being stabilized with PP1M (the treatment dose was not changed in the four months before study inclusion) The mean dose of PP3M was 401. 55 mg Quarterly basis, the following evaluations were performed during a follow-up period of 60 months: The Clinical Global Impression-Schizophrenia scale (CGI-SCH) Treatment adherence, concomitant medication, and the number of hospitalizations. Efficacy values: Percentage of patients who remained free of admissions at the end of 60 months of follow-up. Other evaluation criteria: Average change from baseline visit to the final evaluation as assessed by score obtained on the following scale: GSI-SCH; percentage of patients on antipsychotic monotherapy, and treatment adherence rate.ResultsThe percentage of patients who remained free of admissions at the end of the 60 months was 83.25%. Mean variations from baseline scores at 60 months were: (-0.36 ±0-37) on the GCI-SCH. The rate of adherence to treatment with PP3M after 60 months was 86.58%.ConclusionsIn our study, we found that paliperidone palmitate 3-month formulation effectively prevents admissions under daily clinical practice conditions.DisclosureNo significant relationships.

Impact of 3-Monthly Long-Acting Injectable Paliperidone Palmitate in Schizophrenia: A Retrospective, Real-World Analysis of Population-Based Health Records in Spain.

BackgroundTreatment of schizophrenia requires long-term medication to prevent relapse. Treatment nonadherence may increase the risk of relapse, leading to increased hospitalizations and emergency room (ER) visits. Long-acting injectables (LAIs) such as paliperidone palmitate have improved treatment adherence and therefore symptoms. However, real-world studies comparing 3-monthly LAI formulations with other LAIs and oral antipsychotics (OAs) are scarce.ObjectiveThe objective of this study was to investigate and evaluate the clinical effectiveness of paliperidone palmitate LAI monthly (PP1M; Xeplion®) and 3-monthly (PP3M; Trevicta®) formulations compared with the monthly LAI aripiprazole (AM; Abilify Maintena®) and OAs in Spain.MethodsThis was a retrospective, observational study including 2275 adult patients with schizophrenia in a Spanish population. Data from hospital, primary care, and pharmacy dispensation electronic medical records were obtained between January 2017 and February 2018. The main outcomes included psychiatric hospitalizations and ER visit rates, days on treatment, and treatment persistence.ResultsPatients receiving PP3M had a significantly lower mean hospitalization rate (0.00046 ± standard deviation [SD] 0.00181; p < 0.0001) than other treatment groups. Kaplan–Meier curves revealed that 92.0 and 88.4% of patients receiving PP3M remained hospitalization free by 12 and 18 months, respectively. All treatment groups had at least a twofold significantly higher risk of psychiatric hospitalizations compared with those receiving PP3M or OAs, and the hospitalization risk among the PP3M group was significantly lower (hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.31–0.67). The risk of ER visits was significantly lower with both PP3M and PP1M than with OAs, and lowest with PP3M (HR 0.462 [95% CI 0.29–0.62] and HR 0.833 [95% CI 0.59–0.97], respectively). Time until treatment switch with PP3M was high, with more than 86.5% of patients remaining on treatment at 18 months.ConclusionsPP3M was more effective than OAs and monthly LAIs in improving clinical outcomes for patients with schizophrenia in a real-world setting in Spain.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-022-00917-1.

Effectiveness and Quality of Life with Paliperidone Palmitate 3-Monthly in Comparison with Other Long-Acting Drugs.

PurposeAntipsychotic long-acting injections (AP-LAIs) are indicated for patients affected by schizophrenia especially those with poor treatment adherence.Patients and MethodsTo compare paliperidone palmitate 3-monthly (PP3M), paliperidone palmitate one-monthly (PP1M) and haloperidol decanoate (HAL-D) treatment, we enrolled 90 patients with schizophrenia treated in Mental Health Center with one of the three AP-LAIs for at least six months and followed them for another 6 months. At 6 and 12 months of treatment we administered Clinical Global Impression-Severity, Global Assessment of Functioning and World Health Organization Quality of Life-26 items (WHOQOL-BREF). At 1-year treatment, we evaluated relapses (psychiatric hospitalizations and urgent consultations), side effects and drop-outs.ResultsWe did not highlight any statistically significant difference among the three treatments in relapses and scale scores. Weight increase was significantly higher in PP1M and PP3M groups. Twelve patients (13.3%) discontinued AP-LAI. At 1-year AP-LAI treatment, 69% of patients rated quality of life as “good” or “very good” and 71% declared themselves to be “satisfied” or “very satisfied”.ConclusionHAL-D, PP1M and PP3M 1-year treatments were similarly effective in preventing relapses and improving quality of life and health satisfaction. All discontinuations in the new 3-monthly antipsychotic treatment were caused by patient refusal to continue it.