Dataset Information

Benefit-risk assessment of paliperidone oral extended-release tablet versus monthly injectable for maintenance treatment of schizophrenia.

ABSTRACT: The purpose of this study was to conduct a post-hoc benefit-risk assessment of paliperidone palmitate once-monthly (PP1M) injectable versus oral paliperidone extended-release (ER) in schizophrenia maintenance treatment. The Benefit-Risk Action Team framework was used to structure the analysis based on patient-level data from two similar, double-blind, placebo-controlled relapse studies. Efficacy outcomes were relapse, psychiatric hospitalization, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale, and Positive and Negative Syndrome Scale (PANSS). Safety outcomes were extrapyramidal symptom-related adverse events, weight gain, prolactin-related adverse events, somnolence, orthostatic hypotension, anticholinergic use, fasting plasma glucose, and total cholesterol/high-density lipoprotein. For the first 8 weeks of maintenance treatment, most efficacy outcomes significantly favored PP1M compared with paliperidone ER. Per 1000 patients, there would be 165, 115, 85, and 53 fewer cases of PSP worsening, relapse, PANSS worsening, and hospitalizations, respectively. For the first 40 weeks, PSP worsening significantly favored PP1M (140 fewer cases). Relapse, PANSS, hospitalizations, and Clinical Global Impression-Severity scale showed a consistent pattern favoring PP1M but were not significant. Safety outcomes for both 8-week and 40-week periods demonstrated no statistically significant differences between groups. These analyses suggest a benefit-risk profile favoring PP1M over oral paliperidone ER throughout 40 weeks of treatment, particularly in early treatment.

SUBMITTER: Levitan B

PROVIDER: S-EPMC5049945 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Benefit-risk assessment of paliperidone oral extended-release tablet versus monthly injectable for maintenance treatment of schizophrenia.

Levitan Bennett B Markowitz Michael M Turkoz Ibrahim I Fu Dong-Jing DJ Gopal Srihari S Alphs Larry L

International clinical psychopharmacology 20161101 6

The purpose of this study was to conduct a post-hoc benefit-risk assessment of paliperidone palmitate once-monthly (PP1M) injectable versus oral paliperidone extended-release (ER) in schizophrenia maintenance treatment. The Benefit-Risk Action Team framework was used to structure the analysis based on patient-level data from two similar, double-blind, placebo-controlled relapse studies. Efficacy outcomes were relapse, psychiatric hospitalization, Clinical Global Impression-Severity scale, Person ...[more]

PMID: 27434314

Similar Datasets

Project description:AimsPaliperidone palmitate 3-month (PP3M) represents a new long-acting injectable antipsychotic therapeutic option. This review aims: 1) to summarize available data relating to efficacy, safety, tolerability and costs of PP3M; 2) to describe hospitalization rate, occupational status, treatment preference, satisfaction, adherence and caregiver burden of patients with schizophrenia who participate in PP3M clinical trials; 3) to examine ethical implications, pros and cons of PP3M use and 4) to propose study designs to further assess PP3M.MethodsOn August 21, 2017, a search on PubMed about PPM3, without any filter restriction, was conducted and all available records were analyzed. Records written in a language other than English were excluded.ResultsTwenty-two records were included in this review: 6 reviews, 1 report, 4 pharmacokinetic studies, 2 cost-effectiveness analyses, 1 open-label clinical trial, 2 randomized controlled trials (RCTs), 5 studies based on these 2 RCTs and 1 observational study.DiscussionAccording to these last 9 studies, when compared with placebo, PP3M showed a longer time to relapse and good safety and tolerability profiles. Furthermore, when compared with paliperidone palmitate 1 month (PP1M), PP3M treatment showed: 1) non-inferiority in terms of efficacy, safety, tolerability, rate of hospitalization, symptomatic and functional remission, treatment preference and variations of the occupational status; 2) a longer time to relapse after treatment discontinuation and 3) a similar reduction of the caregiver burden.ConclusionPP3M is the only 3-monthly long-acting injectable antipsychotic available on the market. This makes it a unique option of treatment, which could be chosen both in early and advanced phases of illness. Nonetheless, longer naturalistic follow-up studies, two-arm head-to-head superiority trials and mirror studies, based on real-world samples of patients, are needed to further assess long-term safety and advantages of this new option of treatment and to define patients' sub-populations that would most beneficiate from it.

Project description:PURPOSE:Reducing the dosing frequency of antipsychotics (APs) with long-acting injectables (LAIs) such as once-monthly paliperidone palmitate (PP1M) can improve adherence and clinical outcomes for schizophrenia patients. This US study compared physical and psychiatric comorbidity-related outcomes, AP adherence, healthcare resource utilization (HRU), and costs pre- and post-transition to PP1M among schizophrenia patients treated with oral risperidone/paliperidone pre-PP1M transition. METHODS:Health insurance claims from the IQVIA™ PharMetrics Plus database (01/01/2012-07/31/2018) were used to identify adults with???2 schizophrenia diagnoses,???1 claim for PP1M, and???30 days of treatment with oral risperidone/paliperidone in the 60 days before the first PP1M claim (i.e., the index date). Comorbidity-related outcomes, adherence to APs (measured via the proportion of days covered [PDC]), all-cause per-patient-per-month (PPPM) HRU, and all-cause PPPM medical, pharmacy, and total costs (i.e., sum of medical and pharmacy costs) during the 6-month periods pre- and post-transition to PP1M were compared using generalized estimating equation models adjusted for repeated measurements. Analyses were replicated in the subset of patients with???1 all-cause inpatient stay pre-PP1M transition. FINDINGS:Among 427 schizophrenia patients transitioning from oral risperidone/paliperidone to PP1M, the mean age was 41.1 years and 37.9% were female. Following the PP1M transition, patients were less likely to have claims with a diagnosis for psychoses (odds ratio [OR] 0.41; P?<?0.001), hypertension (OR 0.80; P?=?0.011), depression (OR 0.70; P?<?0.001), drug abuse (OR 0.60; P?<?0.001), substance-related and addictive disorders (OR 0.73; P?=?0.003), bipolar and related disorders (OR 0.59; P?<?0.001), sleep-wake disorders (OR 0.68; P?=?0.017), anxiety disorders (OR 0.78; P?=?0.034), and other conditions that may require a focus of clinical attention (OR 0.58; P?<?0.001). Mean PDC by APs was higher post-PP1M (mean?=?0.81) versus pre-PP1M (mean?=?0.68) transition. Post-PP1M, patients were less likely to have an all-cause emergency room visit (OR 0.51; P?<?0.001) or inpatient stay (OR 0.39; P?<?0.001) compared to pre-PP1M. All-cause total healthcare costs remained similar post- versus pre-transition to PP1M (mean monthly cost difference [MMCD]?=?$228; P?=?0.260). Pharmacy costs increased post-PP1M (MMCD?=?$960; P?<?0.001), but were offset by decreasing medical costs (MMCD?=?- $732; P?<?0.001), largely driven by lower costs related to inpatient stays (MMCD?=?- $695; P?<?0.001) and emergency room visits (MMCD?=?- $63; P?<?0.001). For patients with???1 all-cause inpatient stay pre-PP1M transition (N?=?177), a more pronounced improvement in comorbidity-related outcomes, a more pronounced reduction in HRU, and a reduction in total healthcare costs (MMCD?=?- $1308; P?<?0.001) were observed post-transition to PP1M. IMPLICATIONS:Among schizophrenia patients in the US, transitioning to PP1M following oral risperidone/paliperidone treatment was associated with improved comorbidity-related outcomes, higher adherence, and a reduction in HRU, while remaining cost neutral. Furthermore, patients with???1 all-cause inpatient stay pre-PP1M transition had significantly lower total healthcare costs post-PP1M transition.

Project description:BACKGROUND:A post hoc analysis from a multiphase trial with open-label transition and maintenance phases, a double-blind relapse prevention phase, and an optional open-label extension examined the long-term tolerability with continuous once-monthly injectable paliperidone palmitate 39, 78, 117, or 156 mg (25, 50, 75, or 100 mg equivalents [mg eq] of paliperidone) in subjects with recently diagnosed (?5 years; n = 216) versus chronic illness (>5 years; n = 429) schizophrenia. METHODS:Adverse events reported at a ?2% margin between subgroups were identified. Relative risks (in the recently diagnosed compared with the chronically ill) and 95% confidence intervals (CI) were determined, and CI not including 1 were considered potentially significant. RESULTS:In both subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean exposures were 333.9 ± 271.9 and 308.7 ± 278.3 days in the recently diagnosed and chronic illness subgroups, respectively. Using the criteria outlined in the methods, nasopharyngitis was a potentially significant event reported in more chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163-0.907). Influenza (2.8% versus 0.7%; relative risk 3.9; 95% CI 1.003-15.730) and amenorrhea (3.2% versus 0.9%; relative risk 3.476; 95% CI 1.029-11.744) at endpoint were potentially significant events in more recently diagnosed than chronically ill subjects. Mean weight changes, sedation/somnolence, any extrapyramidal symptom-related or glucose-related events were generally similar between the groups. The mean prolactin level increased in both sexes in both subgroups (changes from baseline of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically ill. CONCLUSION:The long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.

Project description:BackgroundThe utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice.MethodsA systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions - Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis.ResultsEleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient's prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements.ConclusionOur findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.

Project description:BACKGROUND:This post hoc subgroup analysis of a randomized, double-blind trial evaluated the response to treatment with two long-acting injectable atypical antipsychotics, ie, paliperidone palmitate and risperidone long-acting injectable (RLAI), in subjects with schizophrenia experiencing clinically significant symptoms despite recent treatment with oral risperidone only or other oral antipsychotics. METHODS:Adult subjects were eligible for the 13-week, double-blind, double-dummy trial (NCT00589914) if they had an established diagnosis of schizophrenia for at least one year and a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 inclusive at screening. Subjects received either paliperidone palmitate (234 mg, day 1; 156 mg, day 8; then once-monthly flexible dosing) or RLAI (25-50 mg biweekly, with oral risperidone supplementation on days 1-28), plus matched placebo injections/tablets. RESULTS:This post hoc analysis reports data on 747 subjects who, within 2 weeks of starting double-blind study medication, had reportedly received oral risperidone only (paliperidone palmitate group, n = 126; RLAI group, n = 107), other oral antipsychotics (paliperidone palmitate group, n = 199; RLAI group, n = 203), or no antipsychotic (paliperidone palmitate group, n = 56; RLAI group, n = 56). Mean PANSS total scores improved significantly at end point across all subgroups (mean change from baseline ranged from -17.5 to -19.5, all P < 0.0001). Clinical Global Impression-Severity and Personal and Social Performance scale measures also significantly improved from baseline (all P < 0.0001). CONCLUSION:Treatment with paliperidone palmitate or RLAI resulted in a significant reduction in the symptoms of schizophrenia irrespective of previous recent treatment with oral risperidone only or other oral antipsychotics. For subjects who had previously received oral risperidone only, the difference in formulation was the main change in the intervention because the molecule delivered remained the same or similar. These data support the contribution of a long-acting formulation to improving the treatment response and suggest that nonadherence may be a significant contributor to inadequate efficacy of oral formulations in subjects with schizophrenia.

Project description:OBJECTIVE:The objective of this study was to compare persistence, costs, and healthcare resource utilization in patients with schizophrenia and cardiometabolic comorbidities treated with once-monthly paliperidone palmitate or an oral atypical antipsychotic. METHODS:Medicaid data from six states (07/2009-03/2015) were used to identify adults with schizophrenia and cardiometabolic comorbidities initiated on once-monthly paliperidone palmitate or an oral atypical antipsychotic (index date) on 01/2010 or after. Persistence to index medication at 12 months (no gap ≥ 90 days) was compared between patients taking once-monthly paliperidone palmitate and an oral atypical antipsychotic using Chi-squared tests. The 12-month post-index healthcare costs and healthcare resource utilization were compared using multivariate ordinary least squares and Poisson regression, respectively. RESULTS:Selected patients taking once-monthly paliperidone palmitate (n = 371) were younger (mean age: 45.0 vs. 47.5 years, standardized difference = 24%) than patients taking oral atypical antipsychotics (n = 8296). Persistence at 12 months was higher in patients taking once-monthly paliperidone palmitate (40 vs. 33%, p = 0.006). Adjusted all-cause medical costs were lower in patients taking once-monthly paliperidone palmitate vs. patients taking oral atypical antipsychotics (mean monthly cost differences = US $ - 369, p = 0.004) while all-cause pharmacy costs were higher (mean monthly cost differences = US $279, p < 0.001), resulting in no significant difference in total costs (mean monthly cost differences = US $ - 90, p = 0.357). No significant difference was observed in cardiometabolic comorbidity-related pharmacy or medical costs. Compared with patients taking oral atypical antipsychotics, patients taking once-monthly paliperidone palmitate had more schizophrenia-related outpatient visits (incidence rate ratio = 1.44, p < 0.001) but fewer cardiometabolic comorbidity-related inpatient admissions (incidence rate ratio = 0.73, p < 0.001) with shorter lengths of stay (incidence rate ratio = 0.72, p = 0.020), and fewer cardiometabolic comorbidity-related long-term care admissions (incidence rate ratio = 0.56, p = 0.016). CONCLUSIONS:Medicaid beneficiaries with schizophrenia and cardiometabolic comorbidities who were initiated on once-monthly paliperidone palmitate had similar 12-month total healthcare costs compared with oral atypical antipsychotics. Cardiometabolic comorbidity-related utilization of inpatient and long-term care services was lower in patients taking once-monthly paliperidone palmitate.

Project description:Purpose/backgroundThe Phase 3 program for RBP-7000, a once-monthly subcutaneous (SC) extended-release risperidone formulation approved for treatment of schizophrenia, consisted of a double-blind placebo-controlled trial (previously reported) and a 52-week open-label study of monthly RBP-7000 120 mg. The primary objective of the open-label study was to evaluate the long-term safety and tolerability of RBP-7000 in adults with schizophrenia. A secondary objective was to assess long-term maintenance of effectiveness.Methods/proceduresThe 52-week Phase 3 open-label study (NCT02203838) enrolled 92 rollover participants from the double-blind trial (NCT02109562) and 408 stable (Positive and Negative Syndrome Scale [PANSS] total score, ≤70) de novo participants. Participants received up to 13 monthly SC injections of RBP-7000 120 mg. Safety assessments included treatment-emergent adverse events, injection-site assessments, vital signs, laboratory and ECG parameters, extrapyramidal symptoms, and suicidality. Clinical outcomes included the PANSS and Clinical Global Impression-Severity.Findings/resultsOverall, 367 participants (73.4%) reported 1 or more treatment-emergent adverse event; the most common were injection-site pain (13.0%) and weight increase (12.8%). Most participants (>80%) experienced no injection-site reactions. No clinically meaningful changes were observed in laboratory or electrocardiogram values, vital signs, extrapyramidal symptoms, or suicidality. Over 12 months of exposure, mean PANSS scores continued to improve in rollover participants and remained stable among de novo participants. Mean Clinical Global Impression-Severity scores remained stable among all participants.Implications/conclusionsExcept for anticipated injection-site reactions, RBP-7000 demonstrated a favorable safety and tolerability profile similar to oral risperidone. Notably, PANSS scores continued to improve for participants from the pivotal study and remained stable for de novo participants.

Dataset Information

Benefit-risk assessment of paliperidone oral extended-release tablet versus monthly injectable for maintenance treatment of schizophrenia.

Publications

Benefit-risk assessment of paliperidone oral extended-release tablet versus monthly injectable for maintenance treatment of schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets