Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

BACKGROUND: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at week 12 (W12) and maintaining clinical remission at W52 in patients with moderately to severely active ulcerative colitis. Results are presented from the open-label extension study through W104. METHODS: Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders and extended induction responders, including biologic-failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC). RESULTS: Among W52 mirikizumab responders, clinical response at W104 was 74.5%, 87.2%, and 96.7% and clinical remission was 76.6%, 89.0%, and 98.3% for NRI, mNRI, and OC, respectively. Among W52 mirikizumab remitters, clinical response at W104 was 54.0%, 62.8%, and 70.1% and clinical remission was 65.6%, 76.1%, and 84.2%. Using mNRI, remission rates at W104 for W52 clinical remitters were 74.7% corticosteroid-free, 79.5% endoscopic, 63.9% histologic-endoscopic mucosal remission, 85.9% symptomatic, 59.8% bowel urgency, 80.5% Inflammatory Bowel Disease Questionnaire (using NRI), 71.2% histologic-endoscopic mucosal improvement, and 77.5% bowel urgency improvement. Previous biologic-failed vs not-biologic-failed patient data were generally similar. Extended induction mNRI clinical response was 81.9%. Serious adverse events were reported in 5.2% of patients; 2.8% discontinued treatment due to adverse events. CONCLUSIONS: Endoscopic, histologic, symptomatic, and quality-of-life outcomes support the long-term benefit of mirikizumab treatment up to 104 weeks in patients with ulcerative colitis, including biologic-failed patients, with no new safety concerns.

Long-term clinical response/remission, endoscopic, histologic, and symptomatic data from an open-label study in patients with moderately to severely active ulcerative colitis demonstrate that 2-year continuous mirikizumab treatment maintained clinical remission in a majority of induction clinical responders, regardless of previous biologic failure status.

Fragmentation as a novel measure of stability in normalized trajectories of mood and attention measured by ecological momentary assessment.

Electronic diary data, such as that acquired through Ecological Momentary Assessments (EMA), has historically provided novel insights into diverse psychological processes. Analyses of these data typically focus on modeling participant-specific means, variability, and stability. We propose a novel statistical framework to determine participant stability by quantifying fragmentation of standardized trajectories using the following 2-step approach: (1) participant-level EMA scores are normalized, and (2) normalized scores are dichotomized into 2 states, inside and outside a range of 1 standard deviation. Within-participant fragmentation measures were calculated from dichotomized scores and modeled with various covariates. We used this method to study patterns of emotional states and showed that the proposed fragmentation measures differentiate mood disorder subtypes, including Bipolar I (BPI), Bipolar II, and major depressive disorder (MDD) compared with unaffected controls. Fragmentation measures were regressed on the mood disorder subtype, adjusting for age, sex, body mass index, and mean squared successive difference. The analyses revealed decreased stability (more fragmentation) among those with BPI when inside the participant-specific standard range of attention (ß = 0.09, p = .004) and decreased stability among those with MDD inside the standard range of mood (ß = 0.04, p = .039) and attention (ß = 0.05, p = .017). This work provides an illustration of the clinical significance of EMA in characterizing the stability of mood, attention, or other psychological states that may underlie psychological disorders and phenomena. The application of fragmentation provides a novel statistical approach that can characterize within-participant stability beyond currently available traditional approaches. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Altered cortical brain activity in end stage liver disease assessed by multi-channel near-infrared spectroscopy: Associations with delirium.

Delirium is a common and serious psychiatric syndrome caused by an underlying medical condition. It is associated with significant mortality and increased healthcare resource utilization. There are few biological markers of delirium, perhaps related to the etiologic heterogeneity of the syndrome. Functional near-infrared spectroscopy (fNIRS) is an optical topography system to measure changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the cerebral cortex. We examined whether altered cortical brain activity in delirious patients with end stage liver disease (ESLD) is detected by fNIRS. We found that the [oxy-Hb] change during the verbal fluency task (VFT) was reduced in patients with ESLD compared with healthy controls (HC) in the prefrontal and bi-temporal regions. The [oxy-Hb] change during the sustained attention task (SAT) was elevated in patients with ESLD compared to HC in the prefrontal and left temporal regions. Notably, [oxy-Hb] change in the left dorsolateral prefrontal cortex during SAT showed a positive correlation with the severity of delirium. Our results suggest that [oxy-Hb] change in the prefrontal cortex during the sustained attention task measured with fNIRS might serve as a biological marker associated with delirium in ESLD patients.