Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating this population.

4 experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care.

S.C.O.P.E.™ is a freely-available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. S.C.O.P.E.™ provides HCPs with considerations in common clinical scenarios met in inpatient and outpatient settings, as well as questions to consider when patients present to the emergency department. The potential usefulness of LAIs is explored in each scenario. Clinical education videos prepare nurse practitioners, social workers, and case managers to address patient concerns and communicate the benefits of LAI treatment. S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia and the role of LAIs in schizophrenia management.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with schizophrenia.

Four experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care. S.C.O.P.E.™ also includes supportive elements such as an LAI selector.

S.C.O.P.E.™ is a freely available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. To acquaint HCPs with characteristics of common LAIs used in schizophrenia treatment, S.C.O.P.E.™ offers a selector that filters LAIs by approved indication(s), initiation regimen, reconstitution, dosing strengths and frequency, injection volumes and routes, and supply and storage information based on approved product labels. The LAI selector does not provide LAI safety and efficacy data, so HCPs should visit individual product websites for this information. Therefore, S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia, the role of LAIs in schizophrenia management, and the product characteristics of available LAIs.

Teva Branded Pharmaceutical Products R&D, Inc.

Prior studies demonstrated the antipsychotic activity of the dual M1/M4 preferring muscarinic receptor agonist xanomeline in people with schizophrenia and Alzheimer’s disease, but its further clinical development was limited primarily by gastrointestinal side effects. KarXT combines xanomeline and the peripherally restricted muscarinic receptor antagonist trospium chloride. KarXT is designed to preserve xanomeline’s beneficial central nervous system effects while mitigating side effects due to peripheral muscarinic receptor activation. The efficacy and safety of KarXT in schizophrenia were demonstrated in the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials.

The EMERGENT trials randomized people with a recent worsening of positive symptoms warranting hospitalization, Positive and Negative Syndrome Scale (PANSS) total score ≥80, and Clinical Global Impression–Severity (CGI-S) score ≥4. KarXT dosing (xanomeline/trospium) started at 50 mg/20 mg twice daily (BID) and increased to a maximum of 125 mg/30 mg BID. In each trial, the primary efficacy endpoint was change from baseline to week 5 in PANSS total score. Other efficacy measures included change from baseline to week 5 in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, and CGI-S scores. Data from the EMERGENT trials were pooled, and efficacy analyses were conducted in the modified intent-to-treat population, defined as all randomized participants who received ≥1 trial drug dose and had a baseline and ≥1 postbaseline PANSS assessment.

The pooled analyses included 640 participants (KarXT, n=314; placebo, n=326). Across trials, KarXT was associated with a significantly greater reduction in PANSS total score at week 5 compared with placebo (KarXT, -19.4; placebo, -9.6 [least squares mean (LSM) difference, -9.9; 95% CI, -12.4 to -7.3; P<0.0001; Cohen’s d, 0.65]). At week 5, KarXT was also associated with a significantly greater reduction than placebo in PANSS positive subscale (KarXT, -6.3; placebo, -3.1 [LSM difference, -3.2; 95% CI, -4.1 to -2.4; P<0.0001; Cohen’s d, 0.67]), PANSS negative subscale (KarXT, -3.0; placebo, -1.3 [LSM difference, -1.7; 95% CI, -2.4 to -1.0; P<0.0001; Cohen’s d, 0.40]), PANSS Marder negative factor (KarXT, -3.8; placebo, -1.8 [LSM difference, -2.0; 95% CI, -2.8 to -1.2; P<0.0001; Cohen’s d, 0.42]), and CGI-S scores (KarXT, -1.1; placebo, -0.5 [LSM difference, -0.6; 95% CI, -0.8 to -0.4; P<0.0001; Cohen’s d, 0.63]).

In pooled analyses from the EMERGENT trials, KarXT demonstrated statistically significant improvements across efficacy measures with consistent and robust effect sizes. These findings support the potential of KarXT to be first in a new class of medications to treat schizophrenia based on muscarinic receptor agonism and without any direct dopamine D2 receptor blocking activity.

Karuna Therapeutics

Health and social care workers (HSCWs) are at risk of experiencing adverse mental health outcomes (e.g. higher levels of anxiety and depression) because of the COVID-19 pandemic. This can have a detrimental effect on quality of care, the national response to the pandemic and its aftermath.

A longitudinal design provided follow-up evidence on the mental health (changes in prevalence of disease over time) of NHS staff working at a remote health board in Scotland during the COVID-19 pandemic, and investigated the determinants of mental health outcomes over time.

A two-wave longitudinal study was conducted from July to September 2020. Participants self-reported levels of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and mental well-being (Warwick-Edinburgh Mental Well-being Scale) at baseline and 1.5 months later.

The analytic sample of 169 participants, working in community (43%) and hospital (44%) settings, reported substantial levels of depression and anxiety, and low mental well-being at baseline (depression, 30.8%; anxiety, 20.1%; well-being, 31.9%). Although mental health remained mostly constant over time, the proportion of participants meeting the threshold for anxiety increased to 27.2% at follow-up. Multivariable modelling indicated that working with, and disruption because of, COVID-19 were associated with adverse mental health changes over time.

HSCWs working in a remote area with low COVID-19 prevalence reported substantial levels of anxiety and depression, similar to those working in areas with high COVID-19 prevalence. Efforts to support HSCW mental health must remain a priority, and should minimise the adverse effects of working with, and disruption caused by, the COVID-19 pandemic.

Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).

Participants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.

In the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).

In long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.

Neurocrine Biosciences, Inc.

The novel severe acute respiratory coronavirus virus 2 (SARS-CoV-2) was first reported in Wuhan, China, in December 2019 and is notable for being highly contagious and potentially lethal; and SARS-CoV-2 is mainly spread by droplet transmission. The US healthcare system’s response to the COVID-19 pandemic has been challenged by a shortage of personal protective equipment (PPE), especially N95 respirators. Restricted use, reuse, and sanitation of PPE have been widely adopted to provide protection for frontline healthcare workers caring for often critically ill and highly contagious patients. Here, we describe our validated process for N95 respirator sanitation.

Process development, validation, and implementation.

Level 1, urban, academic, medical center.

A multidisciplinary team developed a novel evidence-based process for N95 respirator reprocessing and sanitation using ultraviolet (UV) light. Dose measurement, structural integrity, moisture content, particle filtration, fit testing, and environmental testing were performed for both quality control and validation of the process.

The process achieved UV light dosing for sanitation while maintaining the functional and structural integrity of the N95 respirators, with a daily potential throughput capacity of ∼12,000 masks. This process has supported our health system to provide respiratory PPE to all frontline team members.

This novel method of N95 respirator sanitation can safely enable reuse of the N95 respirators essential for healthcare workers caring for patients with COVID-19. Our high-throughput process can extend local supplies of this critical PPE until the national supply is replenished.

Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).

Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.

In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).

Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.

International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.

This study was sponsored by Neurocrine Biosciences, Inc.

Tardive dyskinesia (TD), a persistent and potentially disabling movement disorder, is associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine (VBZ) is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from two long-term phase 3 studies (KINECT 3 [K3], NCT02274558; KINECT 4 [K4], NCT02405091) and a rollover study (1506, NCT02736955), the long-term outcomes of once-daily VBZ on TD were examined in participants who received 40mg or had a dose reduction from 80 to 40mg.

The effects of VBZ 40mg (as well as VBZ 80mg) were evaluated in the following studies: the pivotal K3 study (6 weeks double-blind, placebo controlled), the extension phase of K3 (42 additional weeks of VBZ, 4 week discontinuation), and the open-label K4 study (48 weeks of VBZ, 4 week discontinuation). Completers from K3 extension and K4 were invited to participate in 1506 (up to 72 additional weeks of VBZ or until commercial availability of VBZ). Few participants reached Week 60 (n=4) or Week 72 (n=0) in the 1506 study before termination. Analyses focused on VBZ 40mg in two populations: pooled K3/K4 (participants who received VBZ 40mg throughout K3 or K4 or who had a dose reduction [80/40mg] during K3 or K4); and 1506 (participants who received VBZ 40mg from beginning of K3 or K4 to last visit in 1506 or who had a dose reduction [80/40mg] at any time). Outcomes for the K3/K4 population included mean change from baseline (CFB) in Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48 of K3 or K4. Outcomes for the 1506 population included a Clinical Global Impression of Severity-Tardive Dyskinesia (CGIS-TD) score ≤2 (“normal, not at all ill” or “borderline ill”).

In the K3/K4 population, AIMS CFB to Week 48 indicated mean TD improvements in participants who received 40mg continuously (40mg, -5.7 [n=54]) and in those who had a dose reduction to 40mg (80/40mg, -6.2 [n=13]). In addition, a majority of these participants had an AIMS response after 48 weeks of treatment (40mg, 53.7%; 80/40mg, 53.8%). In the 1506 population, the percentage of participants who had a CGIS-TD score ≤2 (rating of “normal, not at all ill” or “borderline ill”) at Week 12 was 63.6% (7/11) in the 40mg group and 30.8% (4/13) in the 80/40mg group. Data from Weeks 24 to 60 of 1506 were limited by the small sample sizes (<10 participants each in 40mg or 80/40mg group at each of these visits).

Based on these analyses and results from published studies, VBZ 40mg may be an effective long-term option for some TD patients. Dose reductions from 80 to 40mg, if necessary, did not appear to compromise long-term benefit.

This study was sponsored by Neurocrine Biosciences, Inc.