Resource utilization in patients with schizophrenia who initiated risperidone long-acting therapy: results from the Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE)

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a chronic mental health disorder associated with increased hospital admissions and excessive utilization of outpatient services and long-term care. This analysis examined health care resource utilization from a 24-month observational study of patients with schizophrenia initiated on risperidone long-acting therapy (RLAT).</p> <p>Methods</p> <p>Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE) was a 24-month observational study designed to examine real-world treatment outcomes by prospectively following patients with schizophrenia initiated on RLAT. At baseline visit, prior hospitalization and ER visit dates were obtained for the previous 12 months and subsequent hospitalization visit dates were obtained at 3-month visits, if available. The health care resource utilization outcomes measures observed in this analysis were hospitalizations for any reason, psychiatric-related hospitalizations, and emergency room (ER) visits. Incidence density analysis was used to assess pre-event and postevent rates per person-year (PY).</p> <p>Results</p> <p>The primary medical resource utilization analysis included 435 patients who had a baseline visit, ≥1 postbaseline visits after RLAT initiation, and valid hospitalization dates. The number of hospitalizations and ER visits per PY declined significantly (<it>p </it>< .0001) after initiation with RLAT. A 41% decrease (difference of -0.29 hospitalizations per PY [95% CI: -0.39 to -0.18] from baseline) in hospitalizations for any reason, a 56% decrease (a difference of -0.35 hospitalizations per PY [95% CI: -0.44 to -0.26] from baseline) in psychiatric-related hospitalizations, and a 40% decrease (-0.26 hospitalizations per PY [95% CI: -0.44 to -0.10] from baseline) in ER visits were observed after the baseline period. The percentage of psychiatric-related hospitalizations decreased significantly after RLAT initiation, and patients had fewer inpatient hospitalizations and ER visits (all <it>p </it>< .0001).</p> <p>Conclusion</p> <p>The results suggest that treatment with RLAT may result in decreased hospitalizations for patients with schizophrenia.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00246194">NCT00246194</a></p

Systemic Safety in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration: A Patient-Level Pooled Analysis

Topic This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg versus sham ± verteporfin in patients with neovascular age-related macular degeneration (nAMD). In addition, comparisons of ranibizumab 0.3 mg with sham and ranibizumab 0.5 mg to 0.3 mg were performed. Clinical Relevance Intravitreal anti–vascular endothelial growth factor (VEGF) agents carry potential increased systemic risks, including cardiovascular or cerebrovascular events. Pooled safety analyses allow better interpretation of safety outcomes seen in individual clinical trials, especially for less common events. To our knowledge, this is the largest patient-level pooled analysis of patients with nAMD treated with ranibizumab. Methods Patient-level pooled analysis of data from 7 Genentech- and Novartis-sponsored phase II, III, and IV studies in nAMD that were completed by December 31, 2013. Pairwise comparisons (primary comparison: ranibizumab 0.5 mg [globally approved dose for nAMD] vs. sham or verteporfin) were performed using Cox proportional hazard regression (hazard ratios [HRs], 95% confidence intervals [CIs]) and rates per 100 patient-years. Standardized Medical Dictionary for Regulatory Activities queries (SMQs) and extended searches were used to identify relevant safety endpoints, including arterial thromboembolic events (ATEs), myocardial infarction (MI), stroke or transient ischemic attack (TIA), stroke (excluding TIA), vascular deaths, and major vascular events as defined by the Antiplatelet Trialists' Collaboration (APTC). Results The HRs (95% CIs) for the primary comparison of ranibizumab 0.5 mg (n=480) versus sham or verteporfin (n=462) were 1.16 (0.72–1.88) for ATE, 1.33 (0.59–2.97) for MI, 1.43 (0.54–3.77) for stroke excluding TIA, 1.25 (0.61–2.55) for stroke or TIA, 0.57 (0.18–1.78) for vascular death, and 1.12 (0.64–1.98) for APTC events. Hazard ratio 95% CIs included 1, indicating no significant treatment differences, for all endpoints for comparison of ranibizumab 0.5 mg versus sham or verteporfin. Conclusions The rates of cardiovascular and cerebrovascular events were low in these patients with nAMD and not clinically meaningfully different for patients treated with ranibizumab 0.5 mg versus sham or verteporfin, which supports the favorable benefit–risk profile of ranibizumab in the patient population with nAMD. Pooling these studies allows an analysis with higher power and precision compared with individual study analyses

Adjunctive long-acting risperidone in patients with bipolar disorder who relapse frequently and have active mood symptoms

<p>Abstract</p> <p>Background</p> <p>The objective of this exploratory analysis was to characterize efficacy and onset of action of a 3-month treatment period with risperidone long-acting injection (RLAI), adjunctive to an individual's treatment regimen, in subjects with symptomatic bipolar disorder who relapsed frequently and had significant symptoms of mania and/or depression.</p> <p>Methods</p> <p>Subjects with bipolar disorder with ≥4 mood episodes in the past 12 months entered the open-label stabilization phase preceding a placebo-controlled, double-blind study. Subjects with significant depressive or manic/mixed symptoms at baseline were analyzed. Significant depressive symptoms were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) ≥16 and Young Mania Rating Scale (YMRS) < 16; manic/mixed symptoms were YMRS ≥16 with any MADRS score. Subjects received open-label RLAI (25-50 mg every 2 weeks) for 16 weeks, adjunctive to a subject's individualized treatment for bipolar disorder (mood stabilizers, antidepressants, and/or anxiolytics). Clinical status was evaluated with the Clinical Global Impressions of Bipolar Disorder-Severity (CGI-BP-S) scale and changes on the MADRS and YMRS scales. Within-group changes were evaluated using paired <it>t </it>tests; categorical differences were assessed using Fisher exact test. No adjustment was made for multiplicity.</p> <p>Results</p> <p>162 subjects who relapsed frequently met criteria for significant mood symptoms at open-label baseline; 59/162 (36.4%) had depressive symptoms, 103/162 (63.6%) had manic/mixed symptoms. Most subjects (89.5%) were receiving ≥1 medication for bipolar disorder before enrollment. Significant improvements were observed for the total population on the CGI-BP-S, MADRS, and YMRS scales (p < .001 vs. baseline, all variables). Eighty-two (53.3%) subjects achieved remission at the week 16 LOCF end point. The subpopulation with depressive symptoms at open-label baseline experienced significant improvement on the CGI-BP-S and MADRS scales (p < .001 vs. baseline, all variables). Subjects with manic/mixed symptoms at baseline had significant improvements on the CGI-BP-S and YMRS scales (p < .001 vs. baseline, all variables). No unexpected tolerability findings were observed.</p> <p>Conclusions</p> <p>Exploratory analysis of changes in overall clinical status and depression/mania symptoms in subjects with symptomatic bipolar disorder who relapse frequently showed improvements in each of these areas after treatment with RLAI, adjunctive to a subject's individualized treatment. Prospective controlled studies are needed to confirm these findings.</p

Assessment of effectiveness measures in patients with schizophrenia initiated on risperidone long-acting therapy: the SOURCE study results

<p>Abstract</p> <p>Background</p> <p>To evaluate effectiveness outcomes in a real-world setting in patients with schizophrenia initiating risperidone long-acting therapy (RLAT).</p> <p>Methods</p> <p>This was a 24-month, multicenter, prospective, longitudinal, observational study in patients with schizophrenia who were initiated on RLAT. Physicians could change treatment during the study as clinically warranted. Data were collected at baseline and subsequently every 3 months up to 24 months. Effectiveness outcomes included changes in illness severity as measured by Clinical Global Impression-Severity (CGI-S) scale; functional scores as measured by Personal and Social Performance (PSP) scale, Global Assessment of Functioning (GAF), and Strauss-Carpenter Levels of Functioning (LOF); and health status (Medical Outcomes Survey Short Form-36 [SF-36]). Life-table methodology was used to estimate the cumulative probability of relapse over time. Adverse events were evaluated for safety.</p> <p>Results</p> <p>532 patients were enrolled in the study; 209 (39.3%) completed the 24-month study and 305 (57.3%) had at least 12 months of follow-up data. The mean (SD) age of patients was 42.3 (12.8) years. Most patients were male (66.4%) and either Caucasian (60.3%) or African American (23.7%). All changes in CGI-S from baseline at each subsequent 3-month follow-up visit were statistically significant (<it>p </it>< .0001), indicating improvement in disease severity. Improvements were also noted for the PSP, GAF, and total LOF, indicating improvement in daily functioning and health outcome.</p> <p>Conclusions</p> <p>Patients with schizophrenia who were initiated on RLAT demonstrated improvements in measures of effectiveness within 3 months, which persisted over 24 months.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00246194">NCT00246194</a></p

0762 Baseline characteristics: Solriamfetol’s effect on cognitive Health in Apnea participants during a Randomized Placebo-controlled study (SHARP)

Abstract Introduction Patients with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA) may experience cognitive impairment. Solriamfetol (Sunosi®) is a dopamine/norepinephrine reuptake inhibitor approved in the US and EU to treat EDS associated with OSA. The objective of this study is to assess whether solriamfetol reduces cognitive impairment in patients with EDS associated with OSA. Methods This phase 4, randomized, double-blind, placebo-controlled, crossover trial (NCT04789174) is enrolling adults with OSA and associated EDS (Epworth Sleepiness Scale score &amp;gt;10) and impaired cognitive function defined by an age-adjusted scaled score ≤8 on the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) Coding subtest and a score ≥9 on the British Columbia–Cognitive Complaints Inventory (BC-CCI). Participants are randomized (1:1) to 2 weeks of placebo or solriamfetol (75 mg/day for 3 days, then 150 mg/day) during treatment period 1. After a 1-week washout, participants crossover to receive 2 weeks of the opposite treatment during treatment period 2. Assessments at baseline and after each treatment period include Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding administered 2, 4, 6, and 8 hours post-dose and the BC-CCI. The primary endpoint is change from baseline after each treatment period in the average of 2- and 4-hour post-dose RBANS Coding scores. A secondary endpoint is change from baseline after each treatment period in BC-CCI score. Target enrollment range is 116‒164 participants, pending interim analysis. Enrollment is ongoing; baseline characteristics to date are reported. Results As of October 20th, 2021, 33 participants have been randomized across 20 study sites in North America and Europe. In the intent-to-treat population to date (n=33), mean±SD age is 53.0±10.4, mean±SD BMI is 31.6±4.5, 64% are male, 70% are White (Black or African American, 24%; Asian, 6%), and most (91%) are not Hispanic or Latino. The mean±SD WAIS-IV Coding subtest age-correct scaled score is 6.7±1.3 at baseline, which is below previously observed scores in healthy individuals. Conclusion This ongoing study is the first to examine solriamfetol’s impact on cognitive impairment in participants with OSA. Participants enrolled to date reflect the typical demographics of patients with OSA and demonstrate substantial cognitive impairment. Support (If Any) Jazz Pharmaceuticals </jats:sec

0385 Children, Adolescents, and Their providers: the Narcolepsy Assessment Partnership (CATNAP™) Pediatric Narcolepsy Registry: Baseline Demographics

Abstract Introduction Limited information is available on the natural history, presentation, and management of pediatric narcolepsy. CATNAP™ is a retrospective/prospective, longitudinal, multicenter, web-based pediatric narcolepsy registry (NCT04899947). The primary objectives are to improve understanding of the natural history of pediatric narcolepsy, characterize symptom presentation and diagnosis, and understand treatment practices and outcomes. Methods Eligible children/adolescents (&amp;lt;18 years) had confirmed narcolepsy. Using web-based portals, patients, caregivers, and clinicians completed an initial survey on sociodemographic characteristics; diagnostic, medical, and treatment history; comorbidities; and disease progression. Results Patient/caregiver-reported interim baseline data are included (N=25 patients; mean±SD age: 15.6±2.9 years; 52.0% female; 60.0% White; 64.0% narcolepsy type 1 [NT1]; 28.0% narcolepsy type 2; mean±SD age at narcolepsy diagnosis: 11.0±4.0 years). At narcolepsy diagnosis, the percentages of participants who were &amp;lt;10, 10 to 15, and ≥16 years of age were 36.0%, 52.0%, and 12.0%, respectively. Symptoms at first diagnosis included excessive daytime sleepiness (EDS; 96.0%), cataplexy (64.0%), disrupted sleep (64.0%), vivid dreams (52.0%), and nightmares (40.0%). Comorbid psychiatric disorders were present in 36.0% of participants and included anxiety disorder (20.0%), depression (16.0%), attention-deficit/hyperactivity disorder (ADHD; 12.0%), and panic attacks (8.0%). Misdiagnosis of narcolepsy was reported in 32.0% of participants; alternative diagnoses included anxiety disorder, ADHD, sleep apnea (all 8.0%), and obsessive-compulsive disorder (4.0%). Physician specialties that confirmed narcolepsy diagnosis included neurologists and pediatricians (each 24.0%), pulmonologists (16.0%), pediatric neurologists (12.0%), general practitioners/internists (8.0%), and endocrinologists (4.0%). In participants with NT1 (n=16), warning symptoms for cataplexy were reported by 43.8% and included a sense that cataplexy was imminent without physical symptoms, a sense that time had somewhat suspended, fear/fright, and a feeling of warmness (all 6.3%). At diagnosis, the number of cataplexy episodes per day in order of frequency was 2 (37.5%), 3 (25.0%), 4 (18.8%), and 1 (12.5%). Current medications for narcolepsy included stimulants (60.0%), wake-promoting agents (40.0%), sodium oxybate (32.0%), serotonin-norepinephrine reuptake inhibitors (16.0%), and selective serotonin reuptake inhibitors (8.0%). Conclusion Interim baseline data from CATNAP provide valuable information on the experience and management of pediatric narcolepsy that will facilitate education of patients and caregivers, inform clinical decision-making, and potentially improve treatment strategies. Support (If Any) Jazz Pharmaceuticals. </jats:sec

0390 Efficacy of Lower-Sodium Oxybate in the Treatment of Idiopathic Hypersomnia: Evaluation of Response Based on the Idiopathic Hypersomnia Severity Scale Score

Abstract Introduction Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness (EDS), with sleep inertia and prolonged nighttime sleep as key symptoms in many patients. The Idiopathic Hypersomnia Severity Scale (IHSS) is a 14-item self-reported questionnaire (0–50 score range; higher scores indicate greater severity). The IHSS assesses key symptoms (EDS, sleep inertia, prolonged sleep). An IHSS total score ≤22 is considered normal; the established minimum clinically important difference (MCID) is 4 points. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) treatment on IHSS scores in a phase 3 clinical trial (NCT03533114). Methods Eligible participants with idiopathic hypersomnia began LXB treatment with an open-label treatment titration and optimization period (OLT; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). The IHSS was completed at baseline, during OLT (week [W]1, W4, W8, and end of OLT), and end of SDP. Response was defined as IHSS total score ≤22 or decrease in IHSS total score of ≥4 points after open-label LXB treatment. Results Participants were treatment naive (n=47) or taking alerting agents other than sodium oxybate at study entry (stable doses ≥2 months; n=62). At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total IHSS score ≤22 was 26.1%, 55.3%, 68.1%, 76.6%, and 80.9% (treatment-naive participants), respectively, and 24.2%, 53.2%, 60.7%, 71.0%, and 82.3% (participants taking alerting agents), respectively. At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total IHSS score decrease of ≥4 points was 45.7%, 80.9%, 83.0%, 97.9%, and 93.6% (treatment-naive participants), respectively, and 46.8%, 79.0%, 83.6%, 90.3%, and 98.4% (participants taking alerting agents), respectively. Treatment-emergent adverse events (≥10%) included nausea, headache, dizziness, anxiety, and vomiting. Conclusion Over 80% of participants achieved a clinically meaningful response based upon IHSS total score ≤22, and up to 98% demonstrated a decrease in total IHSS score of ≥4 points at end of SDP. The response rate defined by either parameter increased over the study period. The safety profile of LXB was consistent with that observed in narcolepsy. Support (If Any) Jazz Pharmaceuticals. </jats:sec