Remote Between Visit Monitoring in Inflammatory Bowel Disease Care: A Qualitative Study of CAPTURE-IBD Participants and Care Team Members.

Introduction: We recently showed that CAPTURE-inflammatory bowel disease (IBD)-a care coordination intervention comprised of routine remote monitoring of patient-reported outcomes (PRO) and a care coordinator-triggered care pathway-was more effective at reducing symptom burden for patients with IBD compared to usual care. We aimed to understand how patients and care team providers experienced the intervention and evaluate purported mechanisms of action to plan for future implementation. Methods: In this study, 205 patients were randomized to CAPTURE-IBD (n = 100) or usual care(n = 105). We conducted semi-structured interviews with 16 of the 100 participants in the CAPTURE-IBD arm and 5 care team providers to achieve thematic saturation. We used qualitative rapid analysis to generate a broad understanding of experiences, perceived impact, the coordinator role, and suggested improvements. Results: Findings highlight that the intervention was acceptable and user-friendly, despite concerns regarding increased nursing workload. Both participants and care team providers perceived the intervention as valuable in supporting symptom monitoring, psychosocial care, and between-visit action plans to improve IBD care and health outcomes. However, few participants leveraged the care coordinator as intended. Finally, participants reported that the intervention could be better tailored to capture day-to-day symptom changes and to meet the needs of patients with specific comorbid conditions (eg, ostomies). Conclusions: Remote PRO monitoring is acceptable and may be valuable in improving care management, promoting tight control, and supporting whole health in IBD. Future efforts should focus on testing and implementing refined versions of CAPTURE-IBD tailored to different clinical settings.

Predictors of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease.

BACKGROUND: Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)-like symptoms. Although these symptoms cause significant reductions in quality of life, evidence-based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS-like symptoms in IBD patients with quiescent disease. METHODS: We performed a single-center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 µg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS-like symptoms in IBD patients. KEY RESULTS: A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0-82.0) 63.3 per 1000 person-years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. CONCLUSIONS & INFERENCES: Mood disorder and Crohn's disease were positively associated with IBS-like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS-like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS-like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.

Resolving the Centipede's Dilemma: external focus distance and expertise in applied, continuous skills.

Research has reliably demonstrated that an external focus of attention during skill production enhances performance, retention, and transfer relative to an internal focus on movement mechanics. The optimisation of external focus points, across a range of contexts and performers, is important for effective skill production. Two studies were conducted evaluating the impact of external focus distance in an applied, continuous sports skill (kayak sprinting) with participants of two different expertise levels. In Study 1, using a within-participants design, recreational kayakers (n = 20) were timed sprinting 75 m in a surf ski under proximal external focus, distal external focus, and control conditions. The distal focus (on the finish) (29.75 s) was significantly faster than both other trials (ps < 0.001). The control condition (30.95 s) was significantly faster than the proximal focus (on the boat) (32.37 s) (p = 0.003). The effect size was large (ηp2 = 0.55). In Study 2, specifically trained racers in sprint kayaks (K1s) (n = 16) were timed in a 100 m K1 sprint under the same three conditions as in Study 1. The control condition (28.96 s) was significantly faster than the proximal focus trial (29.83 s) (p = 0.02). The effect size was large (ηp2 = 0.23). There was no significant difference between the distal focus trial (29.03 s) and the other conditions. These findings suggest that focus distance can play a pivotal role in continuous skills. Whilst recreational performers may benefit immediately from a distal focus, this might not be the case for specifically trained athletes. Further, a proximal focus on fitted, passive equipment may be detrimental to performance.

The minimum energy required to build a cell.

Understanding the energy requirements for cell synthesis accurately and comprehensively has been a longstanding challenge. We introduce a computational model that estimates the minimum energy necessary to build any cell from its constituent parts. This method combines omics and internal cell compositions from various sources to calculate the Gibbs Free Energy of biosynthesis independently of specific metabolic pathways. Our public tool, Synercell, can be used with other models for minumum species-specific energy estimations in any well-sequenced species. The energy for synthesising the genome, transcriptome, proteome, and lipid bilayer of four cell types: Escherichia coli, Saccharomyces cerevisiae, an average mammalian cell and JCVI-syn3A were estimated. Their modelled minimum synthesis energies at 298 K were 9.54 × 10 - 11 J/cell, 4.99 × 10 - 9 J/cell, 3.71 × 10 - 7 J/cell and 3.69 × 10 - 12 respectively. Gram-for-gram synthesis of lipid bilayers requires the most energy, followed by the proteome, genome, and transcriptome. The average per gram cost of biomass synthesis is in the 300s of J/g for all four cells. Implications for the generalisability of cell construction and applications to biogeosciences, cellular biology, biotechnology, and astrobiology are discussed.

Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.

Humoral immune response and safety of SARS-CoV-2 vaccination in very early onset inflammatory bowel disease.

Children with very early onset inflammatory bowel disease (VEO-IBD) may respond differently to coronavirus disease 2019 (COVID-19) immunization compared to healthy children or other patients with IBD. We recruited children with VEO-IBD <6 years of age and younger following receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Demographics, IBD characteristics, medication use, adverse events (AEs) and IBD exacerbations were collected. Blood draws (optional) were obtained for measurement of antireceptor binding domain (RBD) IgG antibodies following vaccination. Of 41 participants, none required emergency department visit or hospitalization due to AE, and only one experienced IBD exacerbation. Detectable antibody was present in 19/19 participants who provided blood sample; 6/7 participants (86%) had durable humoral response 12 months postvaccination. Children with VEO-IBD experience robust humoral immune response to COVID-19 immunization. Severe AEs were rare. These findings provide reassurance that children with VEO-IBD respond well and safely to SARS-CoV-2 vaccination.

Organic Input to Titan's Subsurface Ocean Through Impact Cratering.

Titan has an organic-rich atmosphere and surface with a subsurface liquid water ocean that may represent a habitable environment. In this work, we determined the amount of organic material that can be delivered from Titan's surface to its ocean through impact cratering. We assumed that Titan's craters produce impact melt deposits composed of liquid water that can founder in its lower-density ice crust and estimated the amount of organic molecules that could be incorporated into these melt lenses. We used known yields for HCN and Titan haze hydrolysis to determine the amount of glycine produced in the melt lenses and found a range of possible flux rates of glycine from the surface to the subsurface ocean. These ranged from 0 to 1011 mol/Gyr for HCN hydrolysis and from 0 to 1014 mol/Gyr for haze hydrolysis. These fluxes suggest an upper limit for biomass productivity of ∼103 kgC/year from a glycine fermentation metabolism. This upper limit is significantly less than recent estimates of the hypothetical biomass production supported by Enceladus's subsurface ocean. Unless biologically available compounds can be sourced from Titan's interior, or be delivered from the surface by other mechanisms, our calculations suggest that even the most organic-rich ocean world in the Solar System may not be able to support a large biosphere.

Association of Bowel Urgency With Quality-of-Life Measures in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From Phase 3 LUCENT-1 (Induction) and LUCENT-2 (Maintenance) Studies.

Background: Improvement in bowel urgency (BU) was associated with better clinical outcomes in phase 3 LUCENT-1 (induction) and LUCENT-2 (maintenance) studies in moderately-to-severely active ulcerative colitis (UC). We assessed association of BU with quality-of-life (QoL) outcomes. Methods: LUCENT-1: 1162 patients randomized 3:1 to intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W) for 12 weeks. LUCENT-2: 544 mirikizumab induction responders re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo Q4W through Week (W) 40 (W52 of continuous treatment). Patients reported BU severity in the past 24 hours using a validated Urgency Numeric Rating Scale (NRS). In patients with baseline Urgency NRS ≥3, the association between BU Clinically Meaningful Improvement (CMI; ≥3-point decrease) and remission (score 0 or 1) with patient-reported outcomes was assessed at W12 and W52. Results: A significantly greater proportion of patients with versus without BU Remission achieved IBDQ remission (W12: 87.3% vs 42.7%, P < .0001; W52: 91.4% vs 45.5%, p < .0001). Similarly, BU Remission was associated with more patients achieving CMI in SF-36 Physical Component Summary (W12: 69.0% vs 44.4%, P < .0001; W52: 77.5% vs 42.1%, P < .0001) and Mental Component Summary (W12: 53.5% vs 41.0%, P = .0019; W52: 62.0% vs 38.3%, P < .0001) scores. At W12 and W52, patients with BU CMI or Remission showed significant improvements in EQ-5D-5L and Work Productivity and Activity Impairment:UC scores. Significant improvements were also seen in fatigue, abdominal pain, and nocturnal stool. Conclusions: In patients with moderately-to-severely active UC, improvement in BU was associated with improved QoL in phase 3 LUCENT-1 and LUCENT-2 studies. Clinical Studies: LUCENT-1: NCT03518086; LUCENT-2: NCT03524092.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Extended Induction and Prognostic Indicators of Response in Patients Treated with Mirikizumab with Moderately to Severely Active Ulcerative Colitis in the LUCENT Trials.

BACKGROUND: Efficacy and safety of mirikizumab, a p19-targeted anti-interleukin-23 monoclonal antibody, for moderately to severely active ulcerative colitis was demonstrated previously. We evaluated clinical response, baseline characteristics, and clinical status in patients not responding by 12 weeks (W) of induction who then received extended induction treatment. METHOD: Patients unresponsive to 300 mg of intravenous (IV) mirikizumab every 4 weeks by W12 received 3 additional 300 mg IV doses every 4 weeks. Week-4 responders received 200 mg mirikizumab every 4 weeks subcutaneously until W52. Patients responding by W12 but subsequently losing response received rescue therapy with 300 mg IV for 3 doses every 4 weeks. Logistic regression modelling was performed for patients not achieving W12 clinical response to assess baseline characteristics and W12 efficacy parameters and potential prognostic factors of clinical response at W24. RESULTS: Of patients not achieving clinical response during induction, 53.7% achieved response following extended induction. After 52W, 72.2%, 43.1%, and 36.1% of patients achieved clinical response, endoscopic, and clinical remission, respectively. Of induction responders who subsequently lost response, 63.2% and 36.8% achieved symptomatic response and remission, respectively, after receiving rescue therapy No prior biologic or tofacitinib treatment, no immunomodulators at baseline, age older than 40 years, and W12 modified Mayo Score improvement were positively associated with a response to extended induction. The safety profile was similar to initial induction, with 38.3% treatment emergent adverse events, mostly mild. CONCLUSION: With "extended induction," total of 80.3% mirikizumab-treated patients achieved clinical response by W24. Potential prognostic factors determining response include disease severity, disease phenotype, C-reactive protein, and previous biologic therapy.

Extended induction with mirikizumab led to clinical response in more than half of primary nonresponders. Intravenous reinduction therapy in patients losing response during treatment led to more than 60% achieving symptomatic response, confirming the clinical benefit of these treatment strategies for harder to treat patients.

Profiles of Web-based Portal Users with Inflammatory Bowel Disease.

BACKGROUND: Web-based portals can enhance communication between patients and providers to support IBD self-management and improve care. We aimed to identify portal use patterns of patients with inflammatory bowel disease (IBD) to inform future web portal-based interventions and portal design. METHODS: Patients with IBD receiving care at the University of Michigan between 2012 and 2021 were identified. Meta-data from electronic logs of each patient's most recent year of portal use were abstracted. Portal engagement was characterized in terms of intensity (ie, frequency of use); comprehensiveness (ie, number of portal functions used); and duration (ie, quarters per year of portal use). We used k-means clustering, a machine-learning technique, to identify groupings of portal users defined in terms of engagement features. RESULTS: We found 5605 patients with IBD who had accessed their portal account at least once. The average age was 41.2 years (SD 16.7), 3035 (54.2%) were female, and 2214 (39.5%) received immune-targeted therapies. We identified 3 patterns of portal engagement: (1) low intensity users (29.5%); (2) moderate intensity, comprehensive, and sustained users (63.3%); and (3) high intensity, comprehensive, sustained users (7.2%). Patients with more intense, comprehensive, and sustained use of the portal were older, female, with more comorbidities, and were more likely to receive immune-targeted therapies. CONCLUSION: Understanding distinct patterns of portal use can inform portal-based interventions and portal design. Patient portals may be particularly helpful in delivering assistance to those with comorbidities and those receiving immune-targeted therapies-many of whom demonstrate more intense, comprehensive, and sustained portal use.

Inflammatory bowel disease patients have varying patterns of web-based portal engagement that can be characterized into distinct groupings. Portals-based interventions may be particularly helpful for those with comorbidities or receiving immune-targeted therapies­many of whom demonstrate more intense, comprehensive, and sustained use.

Changes in Therapy Are Not Associated With Increased Remission in Patients With Crohn's Disease of the Pouch.

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Efficacy and safety of upadacitinib for 16-week extended induction and 52-week maintenance therapy in patients with moderately to severely active ulcerative colitis.

BACKGROUND: Upadacitinib is an oral, selective Janus kinase inhibitor. AIM: To assess the efficacy and safety of upadacitinib in patients with moderate-to-severe ulcerative colitis following 16-week extended induction therapy, and 52-week maintenance therapy in patients achieving clinical response after 16-week extended induction therapy METHODS: Patients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re-randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52-week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout. RESULTS: Overall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib. CONCLUSIONS: Patients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy. CLINICAL TRIAL REGISTRATION: NCT02819635; NCT03653026.

Fecal calprotectin level is nonlinearly associated with GI pathogen detection in patients with and without inflammatory bowel disease.

Fecal calprotectin (FCP) is used to monitor inflammatory bowel disease (IBD) activity and can also be elevated in gastrointestinal infections. Our study's objective was to quantify the relationship between FCP levels and lab-confirmed infections in people with and without IBD. We performed a cross-sectional study at a tertiary-care center of all encounters during which FCP and gastrointestinal pathogen polymerase-chain reaction (GI PCR) panel testings were conducted. Using non-parametric tests and quantile regression, we compared the FCP levels by IBD status and pathogen detection. There were 3,347 encounters with FCP and GI PCR testings from 2,780 unique individuals between 1 August 2016 and 17 February 2022. Overall, 54.4% had IBD (n = 1,819). Pathogens were detected in 744 encounters (22.2%), and the detection rate did not differ by IBD status. Median FCP without IBD was significantly elevated when a pathogen was detected (64 vs 41 mg/kg, P = 0.0003, normal ≤50.0 mg/kg), but FCP with IBD was not significantly elevated when a pathogen was detected (299 vs 255 mg/kg, P = 0.207). In quantile regression adjusted for age and IBD, pathogen detection was only significantly associated with higher FCP in the lower two quartiles, though IBD remained significantly associated with higher FCP at all levels (P > 0.001). Pathogen detection by GI PCR is associated with elevated FCP, though this relationship is nonlinear and varies by IBD status. Our findings indicate that FCP may be an adjunct to, but not a substitute for, stool pathogen testing.

Use of Upadacitinib in 16 Tofacitinib-refractory Ulcerative Colitis Patients: A Single-center Case 2Series.

We present a case series of 16 patients with ulcerative colitis who received upadacitinib after failing tofacitinib. Five patients (36%) achieved steroid-free clinical remission. Five (62%) demonstrated endoscopic response, while 2 patients (25%) achieved endoscopic remission. Adverse events were low.

Racial Disparity in Esophageal Squamous Cell Carcinoma Treatment and Survival in the United States.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) has a higher incidence and prevalence than esophageal adenocarcinoma among Black individuals in the United States. Black individuals have lower ESCC survival. These racial disparities have not been thoroughly investigated. We examined the disparity in treatment and survival stratified by ESCC stage at diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients with ESCC between 2000 and 2019. The identified cohort was divided into subgroups by race. Patient and cancer characteristics, treatment received, and survival rates were compared across the racial subgroups. RESULTS: A total of 23,768 patients with ESCC were identified. Compared with White individuals, Black individuals were younger and had more distant disease during diagnosis (distant disease: 26.7% vs 23.8%, P < 0.001). Black individuals had lower age-standardized 5-year survival for localized (survival % [95% confidence interval]: 19.3% [16-22.8] vs 27.6% [25.1-30.2]), regional (14.3% [12-16.7] vs 21.1% [19.6-22.7]), and distant (2.9% [1.9-4.1] vs 6.5% [5.5-7.5]) disease. Black individuals were less likely to receive chemotherapy (54.7% vs 57.5%, P = 0.001), radiation (58.5% vs 60.4%, P = 0.03), and surgery (11.4% vs 16.3%, P < 0.0001). DISCUSSION: Black individuals with ESCC have a lower survival rate than White individuals. This could be related to presenting at a later stage but also disparities in which treatments they receive even among individuals with the same stage of disease. To what extent these disparities in receipt of treatment is due to structural racism, social determinants of health, implicit bias, or patient preferences deserves further study.

Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment.

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

Are Depression and Anxiety Underdiagnosed in Socially Vulnerable Patients With Inflammatory Bowel Disease?

INTRODUCTION: Depression and anxiety are highly prevalent among individuals with inflammatory bowel disease (IBD); however, little is understood about how social determinants of health (SDOH) may impact mental health diagnoses in this population. The social vulnerability index (SVI) is a publicly available tool that can be used to study SDOH in IBD patients. METHODS: Home addresses from a retrospective cohort of IBD patients at a single center were used to geocode patients to their individual census tract and corresponding SVI. We used multivariable logistic regression to examine the relationship between SVI and comorbid mental health diagnoses in patients with IBD. Secondarily, data from standardized health questionnaires were then used to determine if patients were adequately screened for depression and anxiety. RESULTS: In all, 9644 patients were included; 18% had a diagnosis of depression, 21% anxiety, and 32% had a composite of "any mental health diagnosis." Depression (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.02-1.56) but not anxiety (OR, 0.87; 95% CI, 0.71-1.06) nor "any mental health diagnosis" (OR, 1.09; 95% CI, 0.92-1.30) was associated with higher levels of social vulnerability. However, overall rates of screening for depression and anxiety were low (15% and 8%, respectively), with the lowest screening rates among the most socially vulnerable (depression 8.2%, anxiety 6.3%). CONCLUSIONS: Disparities in the diagnoses of depression and anxiety for socially vulnerable patients with IBD exist. Awareness of these inequities is the first step toward developing interventions to improve mental health screening, eliminate barriers and bias, and promote referrals for appropriate mental health management.

Socially vulnerable patients with inflammatory bowel disease are more likely to be diagnosed with depression but not anxiety. However, overall rates of screening for depression and anxiety are low, particularly among more socially vulnerable patients.

Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8 week induction therapy (U-ACHIEVE Maintenance): overall results from the randomised, placebo-controlled, double-blind, phase 3 maintenance study.

BACKGROUND: Upadacitinib is an oral, selective, and reversible JAK inhibitor with demonstrated efficacy in patients with moderately to severely active ulcerative colitis in a phase 2b induction trial, two phase 3 induction trials (U-ACHIEVE Induction and U-ACCOMPLISH), and a primary analysis of the first 451 patients entering a subsequent maintenance trial (U-ACHIEVE Maintenance). Here, we present overall results from the entire U-ACHIEVE Maintenance population. METHODS: In this randomised, placebo-controlled, double-blind, phase 3 maintenance study done across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 251 clinical centres in 44 countries, patients aged 16-75 years with moderately to severely active ulcerative colitis (adapted Mayo score 5-9, centrally assessed endoscopic subscore of 2 or 3) for 90 days or more were randomly assigned (2:1) to double-blind upadacitinib 45 mg once daily or placebo induction therapy in the phase 2b induction trial or two phase 3 induction trials. Patients with a clinical response per adapted Mayo score after 8 weeks were randomly reassigned (1:1:1) using web-based interactive response technology to 52 week double-blind maintenance therapy with placebo, upadacitinib 15 mg, or upadacitinib 30 mg once daily. Efficacy was analysed at week 52 in the intention-to-treat population, which included all patients randomly reassigned who received at least one dose of study drug. The primary endpoint was clinical remission per adapted Mayo score. Safety through week 52 was assessed with exposure-adjusted event rates (EAERs; events per 100 patient-years) in upadacitinib 45 mg once daily 8-week induction responders who were enrolled per protocol for 44-week or 52-week maintenance therapy (ie, the intention-to-treat population plus patients who received up to 44 weeks' maintenance therapy under earlier protocol amendments) and received at least one dose of study drug. The study is registered with ClinicalTrials.gov, NCT02819635 and is complete. FINDINGS: Between Sept 3, 2016, and Jan 14, 2021 987 patients received the upadacitinib 45 mg once daily induction therapy in the phase 2b trial, U-ACHIEVE Induction, or U-ACCOMPLISH. 681 patients with a clinical response to the induction therapy (319 from U-ACHIEVE Induction, 341 from U-ACCOMPLISH, and 21 from the phase 2b induction trial) received placebo (n=223), upadacitinib 15 mg once daily (n=225), or upadacitinib 30 mg once daily (n=233) in U-ACHIEVE Maintenance and were included in this analysis. A greater proportion of patients achieved the primary endpoint with upadacitinib 15 mg (40·4%) and 30 mg once daily (53·6%) versus placebo (10·8%; both p<0·0001 vs placebo). For safety, 746 patients were analysed, representing 552·9 patient-years of exposure; the most common grade 3-4 treatment-emergent adverse events were worsening of ulcerative colitis in nine (4%) patients with placebo, and COVID-19 pneumonia and cryptococcal pneumonia in two (1%) patients each with upadacitinib 30 mg once daily. Higher EAERs of the following treatment-emergent events of special interest were observed with upadacitinib versus placebo: herpes zoster (6·0 events per 100 patient-years with upadacitinib 15 mg once daily and 7·3 events per 100 patient-years with upadacitinib 30 mg once daily vs none per 100 patient-years with placebo [12 and 16 vs no events, respectively), hepatic disorders (17·0 and 9·2 vs 5·9 events per 100 patient-years [34 and 20 vs eight events, respectively), creatine phosphokinase elevation (8·0 and 10·1 vs 3·7 events per 100 patient-years [16 and 22 vs five events], respectively), and neutropenia (5·5 and 8·7 vs 5·2 events per 100 patient-years [11 and 19 vs seven events], respectively). One (<1% of patients) adjudicated major adverse cardiovascular event occurred with placebo and one (<1% of patients) with upadacitinib 30 mg once daily (EAERs 0·7 and 0·5 events per 100 patient-years, respectively). Two (1% of patients) venous thromboembolic events occurred with upadacitinib 15 mg once daily and two (1% of patients) with upadacitinib 30 mg once daily (EAERs 1·0 and 0·9 events per 100 patient-years, respectively). All adjudicated major adverse cardiovascular events and venous thromboembolic events with upadacitinib occurred in patients with relevant known risk factors. INTERPRETATION: Consistent with the primary analysis done among a smaller population, both maintenance doses of upadacitinib showed a positive benefit-risk profile in patients with moderately to severely active ulcerative colitis. Upadacitinib represents an effective treatment option for this population, for whom a large unmet need persists. FUNDING: AbbVie.