Hospitalization rates before and after initiation of paliperidone ER in patients with schizophrenia: results from open-label extensions of the US double-blind trials

ABSTRACT

Objective: To assess differences in the number of days hospitalized among schizophrenic patients receiving paliperidone extended-release (paliperidone ER) during the open-label extension (OLE) phases, compared to a similar time period prior to the screening for entry into the double-blind (DB) trials conducted in the United States.

Methods: Mental health-related hospital days during the 52 weeks before entering the DB trials and during the OLE phases were compared. The mean number of hospital days per person per year in the pre- and post-periods was calculated and the statistical significance of pre-post differences was assessed using bootstrap resampling methods. Total person-years were also calculated for the pre- and post-periods to account for different lengths of observation.

Results: Patients' (n = 215) mean (?±?SD) age was 41.2 (?±?11.0) years; most were male (73.0?%?); and black (52.1 vs. 45.1?%?white). The mean (?±?SD) paliperidone ER treatment duration during the OLE phase was 167.0 (?±?145.0) days and the mean (?±?SD) daily dose was 10.5 (?±?2.0) mg. Overall, paliperidone ER patients spent an average (?±?SD) of 13.2 (?±?1.6) and 3.1 (?±?0.7) hospital days per person-year in the pre-and post-periods, respectively (mean?±?SD change 10.0?±?1.8, 95?%?CI 6.5, 13.4, p?<?0.001). Using the 2007 Federal Per Diem Base Rate (i.e., $595.09 per day), this reduction in hospital days would result in an average (?±?SD) cost savings of $5951 (?±?1071) per person per year.

Conclusions: Patients had significantly fewer hospital days in the OLE phase compared to the 1-year period prior to entering the DB trial. Paliperidone ER may play a role in reducing mental health-related hospital days and associated costs. Important study limitations include the lack of a control group, the pre-post design comparing historical data with data collected in the trials which could create a bias due to the mismatch in settings, and patients having more frequent contact with treating physicians and investigators during the trial period, which could favor the outcomes in the OLE phase. Further studies are needed to confirm these findings.     

Flexible dosing with paliperidone ER in the treatment of patients with acutely exacerbated schizophrenia: results from a single-arm,open-label study

Abstract

Objective:

To extend findings from fixed-dose, double-blind, placebo-controlled clinical trials in selected patient populations by using flexibly-dosed oral paliperidone extended-release (ER) in a more naturalistic setting.     

Paliperidone palmitate: Japanese postmarketing mortality results in patients with schizophrenia

Objective: Paliperidone palmitate once-monthly injectable (PP1M) is approved in Japan and other countries for the treatment of schizophrenia. During the 6 month Japanese early postmarketing phase vigilance (EPPV) period, 32 deaths were reported. This report reviews potential contributing factors to the fatal outcomes in the PP1M-treated population.

Research design and methods: All spontaneously reported adverse events following PP1M use received during EPPV from 19 November 2013 to 18 May 2014 were entered into the global safety database and these events were analyzed.

Results: During the EPPV period, 10,962 patients were estimated to have been treated with PP1M in Japan. The mortality reporting rate during this EPPV period was higher than that observed in the US or globally after PP1M launch (5.84, 0.43, and 0.38 per 1000 patient-years, respectively), but was consistent with the mortality incidence rates (10.2 per 1000 person-years) observed during interventional clinical studies in Japan and in observational patient cohorts. Of the 32 deaths reported during the Japanese PP1M EPPV period, 19/32 (59.4%) were in patients over 50 years of age, 23/32 (71.9%) reported cardiovascular risk factors and 25/32 (78.1%) received antipsychotic polypharmacy.

Conclusions: Based on this review of the 32 fatal cases in the PP1M EPPV period, the observed death rate does not necessarily result from a risk with PP1M treatment in Japanese patients. The higher mortality reporting rates in Japan may be attributed to a variety of factors: the effectiveness of mortality reporting in the unique Japanese EPPV program, the advanced age of the fatal cases, high cardiovascular risk factors, multiple underlying diseases and high antipsychotic polypharmacy among the cases with fatal outcomes.     

Baseline characteristics and treatment patterns of patients with schizophrenia initiated on once-every-three-months paliperidone palmitate in a real-world setting

Objectives: Since May 2015, adult patients with schizophrenia adequately treated with once monthly paliperidone palmitate (PP1M) may be transitioned to once-every-three-months paliperidone palmitate (PP3M). This study aims to describe baseline characteristics and treatment patterns of patients with schizophrenia initiated on PP3M in a real-world setting.

Methods: Pharmacy and medical claims from May 2014 to September 2016 for adult patients with schizophrenia initiated on PP3M (index date) in the Symphony Health Solutions database were analyzed. The cohort consisting of all patients and the one restricted to those transitioning from PP1M as per prescribing guideline recommendations were considered. Baseline characteristics were assessed during the 12 month baseline period. PP1M treatment patterns, proportion of days covered (PDC) by mental-health-related medications, and healthcare resource utilization (HRU) patterns were evaluated for each baseline quarter. PP3M treatment patterns were assessed post-index.

Results: Among the 1545 adult patients initiated on PP3M who formed the first cohort, 68.8% transitioned from PP1M based on prescribing guidelines and on an adaptation of the strict clinical trial protocol for PP1M to PP3M transition, forming the second cohort. In both cohorts, the proportion of patients with a PDC ≥80% for antipsychotics, antidepressants, anxiolytics, and mood stabilizers increased while the proportion of patients with ≥1 emergency room, inpatient, or outpatient visit decreased in baseline quarters closer to PP3M initiation. Among patients with ≥4 months of follow-up after the first dose, 85–88% had a second dose. Similarly, among those with ≥4 months of follow-up after the second dose, 87–90% received a third dose.

Conclusions: Patients initiated on PP3M demonstrated decreased HRU and increased adherence in quarters closer to PP3M initiation, and were persistent on their PP3M treatment.     

Transitioning from oral risperidone or paliperidone to once-monthly paliperidone palmitate: a real-world analysis among Veterans Health Administration patients with schizophrenia who have had at least one prior hospitalization

Abstract

Objective: To address gaps in the literature on healthcare resource utilization (HRU) and costs among patients with schizophrenia and prior hospitalization who transition from oral risperidone or paliperidone (oral ris/pali) to once-monthly paliperidone palmitate (PP1M) in a real-world setting by comparing treatment patterns, HRU, and costs 12-months pre- and post-transition to PP1M among Veterans Health Administration (VHA) patients affected by schizophrenia who have had ≥1 hospitalization.

Methods: VHA patients with schizophrenia (aged ≥18?years) who initiated oral ris/pali, had ≥1 all-cause inpatient stay, and transitioned to PP1M from January 2015–March 2017 were included from the VHA database. The first transition date to PP1M was identified as the index date. Patients were required to have continuous health plan eligibility for 12?months pre- and post-PP1M. Outcomes were compared using the Wilcoxon signed-rank and McNemar’s test, as appropriate.

Results: The study included 319 patients (mean [SD] age?=?51.6 [4.2] years) during 12 months of baseline and follow-up. During pre-PP1M transition, 7.2% of the patients were adherent (proportion of days covered [PDC]?≥?80%) to oral ris/pali. Post-PP1M transition, 27.6% of the patients were adherent to PP1M. Comparison of HRU outcomes from the pre- to post-PP1M transition revealed significantly lower all-cause inpatient stays (3.5 vs 1.4, p?<?.0001) and shorter inpatient length of stay (43.4 vs 18.3?days, p?<?.0001). Similar trends were seen for mental health and schizophrenia-related HRU. Cost outcome comparison indicated significantly lower all-cause inpatient costs ($64,702 vs $24,147, p?<?.0001), total medical costs ($87,917 vs $56,947, p?<?.0001), and total costs ($91,181 vs $69,106, p?<?.0001). A similar trend was observed for mental health and schizophrenia-related costs.

Conclusions: Transitioning from oral ris/pali to PP1M may significantly improve HRU and provide potential cost savings in VHA patients with schizophrenia and ≥1 prior hospitalization.     

Efficacy and safety of mirogabalin for the treatment of fibromyalgia: results from three 13-week randomized,double-blind,placebo- and active-controlled,parallel-group studies and a 52-week open-label extension study

Objective: To investigate the efficacy and safety of mirogabalin, an α₂δ ligand, in patients with fibromyalgia (FM).

Methods: In three 13-week, multicenter, double-blind, phase 3 studies (studies A, B, and C), patients with FM (n?=?1293, 1270, and 1301, respectively) were randomized (1:1:1:1) to placebo, pregabalin 150?mg twice daily, mirogabalin 15?mg once daily or mirogabalin 15?mg twice daily. The primary endpoint was the change in weekly average daily worst pain score (ADPS) at week 13. Key secondary endpoints included Patient Global Impression of Change and change in the Fibromyalgia Impact Questionnaire total score. Long-term safety of mirogabalin was assessed in a 52-week extension study.

Results: Neither mirogabalin dose demonstrated a significant ADPS reduction from baseline vs. placebo at week 13 in any of the three studies. Pregabalin significantly reduced ADPS from baseline vs. placebo in studies B and C (p?=?.0008 and .0001, respectively). The effect of mirogabalin compared with placebo on key secondary endpoints was variable across the studies. Mirogabalin was well tolerated by most patients in the phase 3 studies; no unexpected adverse events occurring during the 52-week extension study.

Conclusion: While both mirogabalin doses were well tolerated by most patients and showed potential for reducing pain associated with FM, the primary endpoint of significant pain reduction in patients on mirogabalin compared with placebo was not achieved in any of the three randomized controlled studies.

Clinical trial registration: NCT02146430; NCT02187159; NCT02187471; and NCT02234583 (extension study).     

Flexible dosing with paliperidone ER in the treatment of patients with acutely exacerbated schizophrenia: results from a single-arm, open-label study

Abstract Objective: To extend findings from fixed-dose, double-blind, placebo-controlled clinical trials in selected patient populations by using flexibly-dosed oral paliperidone extended-release (ER) in a more naturalistic setting. Methods: Adults hospitalized with an acute exacerbation of schizophrenia were prospectively treated with open-label flexibly-dosed paliperidone ER 3-12?mg/day for 6 weeks. Results: Overall, 294 patients were treated. The primary endpoint, defined as ≥30% improvement in Positive and Negative Syndrome Scale total scores from baseline to endpoint, was achieved by 66.3% of patients. The percentage of patients rated as at least 'markedly ill' in Clinical Global Impression of Severity scale decreased from baseline (74.1%) to endpoint (20.0%). Patient functioning, assessed by the Personal and Social Performance scale, improved significantly from 50.0?±?14.3 at baseline to 63.6?±?14.9 at endpoint (p?相似文献   

Prevention of episodic migraine with topiramate: a prospective 24-week,open-label,flexible-dose clinical trial with optional 24 weeks follow-up in a community setting

Abstract

Objective:

To explore efficacy and safety outcomes of topiramate for episodic migraine prevention in community practice.     

Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension

Background: We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus.

Research design and methods: We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint.

Results: At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference ?0.92% [95% confidence interval ?1.07%, ?0.76%; p < 0.001]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups.

Conclusions: Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.     

Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety

Background: The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia.

Research design and methods: These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2–5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score.

Results: In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2–5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2–5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores.

Conclusion: PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.     

Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind,randomized, controlled trial,

There has been increasing interest in nutraceutical augmentation strategies to boost the efficacy of antidepressants. This study assessed whether S-adenosylmethionine (SAMe), a methyl donor that occurs naturally in the body, may be of such benefit. We conducted an 8-week, double-blind RCT in which 107 treatment non-remittent outpatients with DSM-5 diagnosed Major Depressive Disorder (MDD) were randomized to either SAMe or placebo adjunctively to antidepressants. One-carbon cycle nutrients, pertinent single nucleotide polymorphisms (SNPs), and BDNF were also analysed as potential moderators of response. A linear mixed-effects model revealed a significant overall reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score across time, however there was no significant between-group difference observed (p?=?0.51). Response rates at Week 8 were 54.3% in the SAMe group and 50.0% in the placebo group, with remission rates 43.5% for SAMe and 38.3% for placebo (all results NS). No effect of SAMe was found on any secondary outcome. Differential response to SAMe was not modified by a range of key genotypes (e.g. COMT), nor reflected in a change of homocysteine, red cell folate, or BDNF. Use of SAMe elicited no significant adverse effects beyond placebo, however it was implicated in one case of serotonin syndrome-like symptoms. This study concludes that 800?mg/day of SAMe is not an effective adjunctive treatment in MDD, and no obvious biomarker reflected any differential response to treatment. Due to such a distinctly high placebo-response (despite rigorous screening), future studies should employ a placebo run-in period and other strategies to minimize placebo response.     

Efficacy and safety of alogliptin added to insulin in Japanese patients with type 2 diabetes: a randomized,double-blind, 12-week,placebo-controlled trial followed by an open-label,long-term extension phase

Objective: To evaluate the efficacy and safety of alogliptin added to insulin in Japanese patients with type 2 diabetes mellitus (T2DM) who are poorly controlled with insulin and diet or exercise.

Study design: This was a randomized, double-blind, 12-week comparative trial of alogliptin and insulin versus placebo and insulin in 179 patients with T2DM followed by a 40-week, open-label phase in 169 patients on alogliptin and insulin.

Primary outcome measure: Change in glycated hemoglobin (HbA1c) from baseline to the end of double-blind phase (week 12).

Results: The change in HbA1c (least squares means) from baseline to week 12 was ?0.96% for the alogliptin and insulin group and ?0.29% for the placebo and insulin group. The point estimate (95% confidence interval) intergroup difference was ?0.66% ([?0.824%, ?0.503%]). In the alogliptin and insulin group, HbA1c started to decrease from week 2 onward and peaked by week 12. The proportions of patients who achieved HbA1c < 8.0, < 7.0 and < 6.0% at week 12 were significantly higher in alogliptin and insulin group (73.0, 23.3 and 1.1%) than in placebo and insulin group (25.0, 5.7 and 0%). Incidences of adverse effects were comparable between groups, with no relevant increases in hypoglycemia or weight gain seen.

Conclusions: Alogliptin 25 mg/day was effective and well tolerated when added to insulin in Japanese patients with inadequately controlled T2DM.     

Impact of clinical pharmacist engagement in ward teams on the number of drug-related readmissions among older patients with dementia or cognitive impairment: An economic evaluation

Background

Clinical pharmacists play an increasing role in the pharmacological treatment of hospital-admitted older patients with dementia or cognitive impairment. In an earlier randomised controlled trial, clinical pharmacist involvement in the ward team could significantly reduce drug-related readmissions in patient subgroups. However, the economic impact of the intervention has not been addressed so far.

Significant immunomodulatory properties of curcumin in patients with osteoarthritis; a successful clinical trial in Iran

Osteoarthritis (OA) routinely is known as a multifactorial degenerative joint disease. This trial aimed to assess the curcumin (an active element of turmeric) effects on the immune responses in OA patients. Thirty patients were selected according to the American College of Rheumatology (ACR) criteria and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and equally divided into the two groups; intervention (received Sinacurcumin® 80 mg daily) and placebo, followed for 3 months. In the intervention group, our data showed a noticeably decrease in Visual Analog Score (VAS), C-reactive protein (CRP), CD4⁺ and CD8⁺ T cells, Th17 cells and B cells frequency. Additionally, Treg cells indicated a significant increase and Treg/Th17 cells ratio showed a meaningfully shifted toward Treg lymphocytes. In conclusion, our data indicated that clinical manifestation was ameliorated considerably following the administration of curcumin. Moreover, our data demonstrated the immunomodulatory effects of curcumin in OA patients.     

Hospitalization rates among patients with community-acquired pneumonia treated with telithromycin vs clarithromycin: results from two randomized,double-blind,clinical trials

SUMMARY

Aims: To compare hospitalization rates among patients with community-acquired pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on pooled data from two randomized, double-blind, multinational clinical trials.

Patients and methods: Adult patients with CAP eligible for oral therapy (Study 1, n = 448; Study 2, n = 575) received telithromycin 800?mg once daily for 10 (Study 1, 2-arms), 5 or 7 (Study 2, 3-arms) days, or clarithromycin 500?mg twice daily for 10?days. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use, as well as CAP-related length of hospital stay and hospitalization costs, were compared by treatment group (intent to treat populations) up until the late post-therapy visit (Days 31–36). Study investigators blinded to treatment regimen assessed whether hospital admissions were CAP related.

Results: Despite equivalent clinical efficacy for telithromycin vs clarithromycin in the clinically evaluable per-protocol populations (n = 784) (88.8% [428/482] vs 90.1% [272/302] – difference: –1.3%; 95% CI: –6.0, 3.4), telithromycin treatment for 5, 7, or 10?days was associated with significantly fewer CAP-related hospitalizations (?p = 0.023) and CAP-related hospital days (?p = 0.025) vs clarithromycin (reduction of 2.3 hospitalizations and 23.4 hospital days per 100 patients). Accordingly, estimated CAP-related hospitalization costs were significantly lower (?p = 0.025) for telithromycin recipients (US$30?231 less per 100 patients). CAP-related hospitalizations, duration of hospital stay, and hospitalization costs for 7- to 10-day telithromycin – the approved dosing regimen for CAP – were significantly lower (?p = 0.023, 0.025, and 0.025, respectively) than for clarithromycin.

Conclusions: Data from this study indicate that telithromycin 800?mg once daily for 5, 7, or 10?days provides an effective therapy for patients with CAP, and may be associated with fewer CAP-related hospitalizations and hospital days than clarithromycin 500?mg twice daily for 10?days. Treatment with telithromycin could, therefore, potentially translate into cost savings in the management of CAP.     

Short-term effects of a brief intervention to reduce alcohol use and sexual risk among homeless young adults: results from a randomized controlled trial

Background: Homeless young adults are more likely than their never-homeless counterparts to abuse alcohol and engage in risky sexual behaviors, yet no interventions to simultaneously reduce both these behaviors among this vulnerable population have been systematically designed and evaluated. We therefore developed a brief intervention (BI) to reduce both alcohol use and sexual risk behaviors among homeless young adults. The results of a randomized trial testing the BI against an education comparison (EC) are presented.

Method: Young adults (N?=?61; age 17–22 years) from an urban, Northeastern crisis shelter were randomly assigned to either the two-session, individual-level BI or a time-matched, two-session, individual-level EC. Generalized linear mixed models for repeated measures determined effects of treatment condition on outcomes.

Results: The BI significantly increased participant readiness to change alcohol use. However, it did not significantly decrease primary alcohol or HIV sexual risk outcomes, independently or relative to EC (all ps > 0.05). Participants in the EC reduced times engaged in unprotected sex between baseline and post-intervention to a significantly greater extent (p?Conclusions: Findings suggest that the BI was acceptable and successful in getting participants to consider changing their drinking. However, lack of change in alcohol and sexual behavior outcomes indicates the need for further research to determine how to translate readiness to change into actual behavioral change among homeless young adults.