Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia

Berwaerts, Joris; Liu, Yanning; Gopal, Srihari; Nuamah, Isaac; Xu, Haiyan; Savitz, Adam; Coppola, Danielle; Schotte, A.; Remmerie, Bart; Maruta, N.; Hough, David

doi:10.1001/jamapsychiatry.2015.0241

Cited by 174 publications

(223 citation statements)

References 29 publications

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“…This finding and findings from the current study are consistent with the requirement from the prescribing guidelines that patients be adequately treated with PP1M prior to the transition to PP3M. In phase 3 trials, low symptom severity, consistent with low utilization of emergency room and inpatient services, was part of the requirements to be considered adequately treated [20,21]. Adherence to PP3M was also similar to the current study, Fig.…”

Section: Discussionsupporting

confidence: 89%

“…[19] Prescription guidelines for PP3M recommend the following dose conversion from the last dose of PP1M to the first dose of PP3M (PP1M dose → PP3M dose): 78 mg → 273 mg, 117 mg → 410 mg, 156 mg → 546 mg, or 234 mg → 819 mg. Prior to FDA approval in 2015, the safety and efficacy of PP3M were demonstrated in two double-blind, randomized clinical trials [20,21]. While patients' characteristics and treatment patterns during the period prior to PP3M initiation have been assessed [22], there is a need to assess the impact of transitioning to PP3M on treatment adherence, healthcare resource utilization (HRU), and costs.…”

Section: Introductionmentioning

confidence: 99%

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Adherence, Healthcare Resource Utilization, and Costs in Medicaid Beneficiaries with Schizophrenia Transitioning from Once-Monthly to Once-Every-3-Months Paliperidone Palmitate

Émond

Joshi

Khoury

et al. 2018

PharmacoEconomics Open

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Objectives The aim was to compare adherence to antipsychotics (APs), healthcare resource utilization (HRU), and costs before and after once-every-3-months paliperidone palmitate (PP3M) initiation in patients with schizophrenia. Methods Medicaid data (Iowa, Kansas, and Missouri; 1/2014-3/2017) were used to identify adults with at least one PP3M claim, ≥ 12 months of pre-index enrollment, and at least two schizophrenia diagnoses. Adequate treatment with once-monthly paliperidone palmitate (PP1M) was required pre-PP3M transition. Generalized estimating equations were used to assess linear trends in adherence to APs, HRU, and costs over the four quarters pre-PP3M transition, and to compare monthly HRU and costs 6 months pre-and 12 months post-PP3M transition as well as adherence to APs 12 months pre-and post-PP3M transition. Results Among 324 patients initiated on PP3M, the mean age was 41.4 years and 36.1% were females. Over the four quarters pre-PP3M transition, the monthly number of emergency room visits, medical costs, and inpatient costs decreased, while pharmacy costs and adherence to APs increased. For patients with ≥ 12 months of follow-up (n = 151), adherence to APs (66.2 vs. 70.2%, p = 0.3758), total (US$3371 vs. US$3456; p = 0.7000), pharmacy (US$1805 vs. US$1870; p = 0.2960), and medical costs (US$1565 vs. US$1586; p = 0.9040) remained similar pre-and post-PP3M transition, while mean monthly number of 1-day mental institute visits (1.71 vs. 1.51; p < 0.01) and associated costs (US$260 vs. US$232, p = 0.01) decreased. Conclusions Adherence to APs, HRU, and costs were similar pre-and post-PP3M transition, suggesting that PP3M has no impact on monthly costs for patients adequately treated with PP1M, with the added flexibility of once-every-3-months dosing. Key Points for Decision MakersOver the four quarters before once-every-3-months paliperidone palmitate (PP3M) transition, adherence to antipsychotics significantly improved and the increase in pharmacy costs was offset by decreasing medical costs, driven by a decrease in inpatient costs.Adherence to antipsychotics, monthly healthcare resource utilization, and monthly Medicaid spending remained similar before and after PP3M transition. These findings suggest that for patients adequately treated with once-monthly paliperidone palmitate, the transition to PP3M has no impact on monthly healthcare costs, with the added flexibility of once-every-3-months dosing.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Adherence, Healthcare Resource Utilization, and Costs in Medicaid Beneficiaries with Schizophrenia Transitioning from Once-Monthly to Once-Every-3-Months Paliperidone Palmitate

Émond

Joshi

Khoury

et al. 2018

PharmacoEconomics Open

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“…formulation of paliperidone offers longer injection intervals than currently available LAI formulations. A double-blind RCT showed superiority of 3-month paliperidone palmitate over placebo for delaying time to relapse of symptoms (hazard ratio = 3.81) [57]. The 3 month formulation was also compared to monthly paliperidone palmitate in a non-inferiority study demonstrating a comparably low relapse risk in both groups [58].…”

Section: ) Im Depot Antipsychoticsmentioning

confidence: 99%

Pharmacological Treatment of Schizophrenia:

Fleischhacker

Miyamoto

2016

CNPT

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In the past decade, four main topics have shaped research and clinical practice. 1) In randomized controlled trials, researchers have investigated whether treating prodromal symptoms of schizophrenia helps to reduce the conversion risk to full-blown schizophrenia. Results are ambiguous and the discussion on whether or not an intervention at the stage is justified is ongoing. 2) Following the enhanced understanding of the pathophysiology of schizophrenia, also with respect to specific symptom domains, pharmacological targets beyond D 2 receptor antagonism have been explored. Much work and enthusiasm has revolved around nicotinergic and glutamatergic compounds, so far with mostly discouraging results. 3) Several new-generation antipsychotics have become available as long-acting formulations. All of them have demonstrated a significant positive impact on relapse rates in placebo controlled studies. Whether these compounds also have advantages over first-generation depots and/or oral antipsychotics is still debated. The development of an inhalable antipsychotic has complemented the treatment options for the management of acutely agitated patients. 4) Lastly, attempts from various perspectives, including genetics and neuroimaging, have investigated whether it is possible to predict treatment response and drug safety. Although some look promising, they have not yet reached a stage in which they can be applied to everyday clinical practice. What has become clear, though, is that early non response predicts late non response, leading to the recommendation to switch antipsychotics much earlier than stated in most treatment guidelines.

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“…The main innovation of PP3M relies in a much slower release in the bloodstream as compared with PP1M. This Commentary critically appraises the clinical data reported in the EMA document, and attempts to identify some of the challenging issues related to the use of PP3M in everyday practice.The EMA report covers two randomised studies: one phase-3, randomised, double-blind, placebocontrolled trial comparing PP3M v. placebo (Berwaerts et al 2015), and one phase-3, randomised, double-blind, head-to-head, non-inferiority trial, comparing PP3M v. PP1M (Savitz et al 2016).The placebo-controlled trial included 305 randomised subjects in the double-blind phase and showed the superiority of PP3M over placebo in terms of relapse prevention (hazard ratio (HR) 3.45; 95% * Address for correspondence: Dr G. Ostuzzi, Section of Psychiatry, University of Verona, Ospedale Policlinico GB Rossi, Piazzale L.A. Scuro, 10 -37134 Verona, Italy.(Email: giovanni.ostuzzi@gmail.com)Epidemiology and Psychiatric Sciences (2017), 26, 231-233. …”

mentioning

confidence: 99%

“…The EMA report covers two randomised studies: one phase-3, randomised, double-blind, placebocontrolled trial comparing PP3M v. placebo (Berwaerts et al 2015), and one phase-3, randomised, double-blind, head-to-head, non-inferiority trial, comparing PP3M v. PP1M (Savitz et al 2016).…”

mentioning

confidence: 99%

New EMA report on paliperidone 3-month injections: taking clinical and policy decisions without an adequate evidence base

Ostuzzi

Papola

Gastaldon

et al. 2016

Epidemiol Psychiatr Sci

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This Section of Epidemiology and Psychiatric Sciences appears in each issue of the Journal to stress the role of the epidemiological approach to promote advances in the field of clinical psychopharmacology, with a particular attention to controversial findings. The ultimate aims are to help develop a more critical attitude towards the results of research studies published in the international literature, to promote original research projects with higher methodological standards, and to implement the most relevant results of research in every-day clinical practice. These contributions are written in house by the journal's editorial team or commissioned by the Section Editor (no more than 1000 words, short unstructured abstract, 4 key-words, one Table or Three-month long-acting paliperidone is a new, recently marketed, formulation of paliperidone, characterised by the longest available dosing interval among long-acting antipsychotics. The clinical profile of 3-month long-acting paliperidone was recently summarised by the European Medicines Agency (EMA) in a public assessment report, released in April 2016. In this commentary, the main strengths and limitations of the EMA assessment report were appraised and discussed, in order to highlight possible implications for clinical practice, future research and regulatory practices for drug approval. In April 2016, the European Medicines Agency (EMA) released a public assessment report on paliperidone palmitate 3-month injections (PP3M), a new longacting injectable (LAI) formulation of paliperidone that requires an injection once every third month. This new formulation adds to other two already in use formulations: an oral prolonged-release tablet formulation, and a 1-month long-acting formulation (PP1M). The EMA document reported a positive opinion for granting a marketing authorisation for four new strengths of PP3M, with an indication for the maintenance treatment of schizophrenia in adult patients who have been adequately treated with PP1M (European Medicines Agency, Committee for Medicinal Products for Human Use, 2016). The main innovation of PP3M relies in a much slower release in the bloodstream as compared with PP1M. This Commentary critically appraises the clinical data reported in the EMA document, and attempts to identify some of the challenging issues related to the use of PP3M in everyday practice.The EMA report covers two randomised studies: one phase-3, randomised, double-blind, placebocontrolled trial comparing PP3M v. placebo (Berwaerts et al. 2015), and one phase-3, randomised, double-blind, head-to-head, non-inferiority trial, comparing PP3M v. PP1M (Savitz et al. 2016).The placebo-controlled trial included 305 randomised subjects in the double-blind phase and showed the superiority of PP3M over placebo in terms of relapse prevention (hazard ratio (HR) 3.45; 95% * Address for correspondence: Dr G. Ostuzzi, Section of Psychiatry, University of Verona, Ospedale Policlinico GB Rossi, Piazzale L.A. Scuro, 10 -37134 Verona, Italy.(Email: giovanni.ostuzzi@gm...

show abstract

Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia

Cited by 174 publications

References 29 publications

Adherence, Healthcare Resource Utilization, and Costs in Medicaid Beneficiaries with Schizophrenia Transitioning from Once-Monthly to Once-Every-3-Months Paliperidone Palmitate

Adherence, Healthcare Resource Utilization, and Costs in Medicaid Beneficiaries with Schizophrenia Transitioning from Once-Monthly to Once-Every-3-Months Paliperidone Palmitate

Pharmacological Treatment of Schizophrenia:

New EMA report on paliperidone 3-month injections: taking clinical and policy decisions without an adequate evidence base

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