Janssen (Ireland)

IntroductionTreatment resistant depression (TRD) affects approximately 10–30% of patients with major depressive disorder, and most patients with TRD do not respond to real-world treatments (RWT). Treatment with esketamine nasal spray (NS) plus a selective serotonin or serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) has significant long-term clinical benefit over RWT in patients with TRD. However, the impact on patient-reported function remains to be determined.MethodsThe ICEBERG analysis was an indirect treatment comparison performed using data from two studies of patients with TRD: SUSTAIN-2 (esketamine NS; NCT02497287) and the European Observational TRD Cohort (EOTC; RWT; NCT03373253; clinicaltrials.gov). Here, patient−reported functional remission, assessed using the Sheehan Disability Scale (SDS), was defined as SDS ≤6 at Month 6. Analyses were conducted using propensity score re−weighting and multivariable models based on 18 covariates.ResultsAt Month 6, the probability of functional remission in esketamine NS−treated patients from SUSTAIN-2 (n=512) was 25.6% (95% confidence interval [CI] 21.8–29.4), while the adjusted probability for RWT patients from the EOTC (n=184) was 11.5% (95% CI 6.9–16.1; relative risk: 2.226 [95% CI 1.451–3.416]; p=0.0003). In the total combined population (N=696), patients who did not achieve clinical response or remission had a low probability of achieving functional remission (5.84% and 8.76%, respectively). However, for patients who did achieve clinical response or remission, the probability of achieving functional remission was greater (43.38% and 54.15%, respectively), although many still did not achieve this status.ConclusionsFor patients with TRD, esketamine NS had a significant functional benefit versus RWT after 6 months of treatment. Irrespective of treatment, achievement of clinical response or remission was insufficient to attain functional remission. Nevertheless, clinical remission increased the likelihood of achieving functional remission, further supporting an important role for clinical remission in for the path towards functional recovery.

IntroductionCirculating tumour cells (CTC) disseminate from a tumour into the blood circulation with the potential to form distant metastases, thus making them promising prognostic biomarkers. There is a lack of data exploring the relationship between CTC status and primary tumour size (PTS) of the pelvic mass in epithelial ovarian carcinomas (EOC). This study aimed to examine this relationship in high-grade serous carcinomas (HGSC) and non-HGSC EOC.MethodsPeripheral blood samples were collected from 52 treatment-naive patients (46 HGSC, 6 non-HGSC). A subset underwent ovarian vein sampling during primary cytoreductive surgery (11 HGSC, 6 non-HGSC). Whole blood was enriched using the Parsortix®PR1 system. CTCs were enumerated by immunophenotyping: EpCAMpos/panCytokeratinpos,Hoechstpos,CD45neg. PTS (maximum dimension) was recorded from baseline CT scans. The cut-off for CTC status (positive/negative) was set at 1.ResultsIn advanced HGSC (III, IV), there was no statistical difference in peripheral CTC count per 7.5mL blood or PTS, although a trend towards higher peripheral CTC count and smaller PTS was observed in stage III versus stage IV. CTCpos HGSC ovarian vein samples had significantly smaller PTS than HGSC ovarian vein CTCnegpatients (p=0.0121). HGSC ovarian vein CTC count also inversely correlated with PTS (r=-0.7356, p=0.0128). Conversely, in non-HGSC, there was a trend towards larger PTS in CTCpos ovarian vein samples compared to CTCneg ovarian vein samples.Conclusion/ImplicationsTo our knowledge, this is the first study exploring the relationship between CTCs and PTS in EOC. The inverse correlation between CTCs and PTS in HGSC likely stems from the extensive peritoneal seeding characteristic of its biology. EV290/#1177 Figure 1

The efficacy of esketamine nasal spray (NS) as a rapid-acting agent for treatment resistant depression (TRD) was demonstrated in comparisons with placebo, when both were given in addition to a newly initiated selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI). How esketamine NS compares with commonly used real-world (RW) polypharmacy treatment strategies is not known. ICEBERG was an adjusted indirect treatment comparison that analysed data from SUSTAIN-2 (NCT02497287; clinicaltrials.gov), a long-term, open-label study of esketamine NS plus SSRI/SNRI, and the European Observational TRD Cohort (EOTC; NCT03373253; clinicaltrials.gov), an observational study of routine clinical practice. Data were compared between patients receiving esketamine NS (SUSTAIN-2) and those from the EOTC treated with polypharmacy treatment strategies, either combination or augmentation. Analyses were adjusted for potential confounders, using rescaled average treatment effect among treated estimates. Threshold analyses were conducted to assess potential impact of unmeasured confounders on the robustness of analyses where esketamine NS was found to be significantly superior. Sensitivity analyses were used to understand the impact of analysis method selection and data handling. Esketamine NS treatment resulted in a higher probability of 6-month response (49.7% [95% confidence interval (CI) 45.6-53.9]) and remission (33.6% [95% CI 29.7-37.6]) versus RW polypharmacy (26.8% [95% CI 21.0-32.5] and 19.4%, [95% CI 14.2-24.6], respectively). Relative risk calculations showed esketamine NS was 1.859 (95% CI 1.474-2.345; p < 0.0001) times as likely to result in response and 1.735 (1.297-2.322; p = 0.0002) times as likely to result in remission versus RW polypharmacy at 6 months. Threshold and extensive sensitivity analyses supported that analyses of esketamine NS superiority were robust. ICEBERG supports esketamine NS being superior to current RW individualized polypharmacy strategies, including augmentation, with benefits extending beyond acute use, to improved chance of 6-month response and remission. While unobserved confounding factors may certainly impact results of an indirect comparison, threshold analysis supported a low likelihood of this affecting the conclusions.To view an animated summary of this publication, please click on the Supplementary video.

Abstract The European Medicines Agency approved ustekinumab for psoriasis treatment in adolescents (12–17 years) in 2015 (CADMUS trial), and children (6–11 years) in 2020. Interim results are reported from a post-authorization study (NCT03218488) evaluating the long-term safety profile of ustekinumab. This ongoing, prospective, observational, multicentre study enrolled patients (6–17 years) diagnosed with moderate-to-severe plaque psoriasis initiating ustekinumab. Clinical data and all adverse events (AEs) through approximately 54 months (data cut-off) are reported. Younger children (6–11 years) were included later in the study. Data are reported by age (younger cohort, 6–11; older cohort, 12–17). At data cut-off, 85 patients, 10 younger (median follow-up, 0.24 years) and 75 older (median follow-up, 1.69 years), had been enrolled. Ustekinumab therapy was discontinued in 11 (12.9%) patients, all from the older cohort. Overall, 50/85 (58.8%) patients reported 290 AEs and 27 (31.8%) reported 96 AEs considered related to ustekinumab. The most commonly reported AEs were nasopharyngitis (n = 8, 9.4%), fatigue (n = 7, 8.2%) and headache (n = 7, 8.2%). Most AEs were mild and did not result in treatment change. Nine (10.6%) patients reported 13 serious AEs; one (appendicitis) was considered related to ustekinumab. One younger patient reported two AEs considered related to ustekinumab, although neither was serious and therapy continued. No malignancies or deaths were reported in either cohort. These findings revealed no new safety concerns and are generally consistent with the known safety profile for ustekinumab in paediatric patients.

The objectives of this analysis were to examine how patients' global severity with Alzheimer's disease (AD) relates to costs of care and explore the incremental effects of global severity measured by the clinical dementia rating (CDR) scale on these costs for patients in Spain. The Codep-EA study is an 18-multicenter, cross-sectional, observational study among patients (343) with AD according to the CDR score and their caregivers in Spain. The data obtained included (in addition to clinical measures) also socio-demographic data concerning the patient and its caregiver. Cost analyses were based on resource use for medical care, social care, caregiver productivity losses, and informal caregiver time reported in the resource utilization in dementia (RUD). Lite instrument and a complementary questionnaire. Multivariate regression analysis was used to model the effects of global severity and other socio-demographic and clinical variables on cost of care. The mean (standard deviation) costs per patient over 6 months for direct medical, social care, indirect and informal care costs, were estimated at €1,028.1 (1,655.0), €843.8 (2,684.8), €464.2 (1,639.0) and €33,232.2 (30,898.9), respectively. Dementia severity, as having a CDR score 0.5, 2, or 3 with CDR score 1 being the reference group were all independently and significantly associated with informal care costs. Whereas having a CDR score of 2 was also significantly related with social care costs, a CDR score of 3 was associated with most cost components including direct medical, social care, and total costs, all compared to the reference group. The costs of care for patients with AD in Spain are substantial, with informal care accounting for the greatest part. Dementia severity, measured by CDR score, showed that with increasing severity of the disease, direct medical, social care, informal care and total costs augmented.