Crohn's & Colitis 360最新文献

Objectives: Fatigue is commonly reported in patients with Crohn's disease (CD) and ulcerative colitis (UC), including patients with inactive disease. We explored the impact of fatigue on healthcare utilization (HCU) and work productivity and activity impairment (WPAI).

Methods: Data collected between 2017 and 2022 were analyzed from the CorEvitas IBD Registry. We compared HCU and WPAI among subjects with high fatigue (PROMIS ≥55) versus low fatigue at enrollment and subjects whose fatigue score worsened or persisted versus low fatigue at 6 months. HCU was defined as an inflammatory bowel disease-related hospitalization or emergency room visit. WPAI included presenteeism, absenteeism, and lost WPAI. Logistic regression analysis was performed.

Results: Study patients (640 CD, 569 UC) reported high rates of fatigue, 47% in CD and 38% in UC, that persisted at least 6 months in 88%-89% of patients. Patients with UC with high fatigue had 3-fold higher rates of HCU and 2-3-fold more absenteeism and activity impairment than patients with low fatigue. Patients with CD with high fatigue had no difference in HCU but did experience 2-4-fold more absenteeism, presenteeism, work productivity loss, and activity impairment. On subgroup analysis of patients in remission, those with high fatigue did not have higher rates of HCU but continued to have higher rates of WPAI.

Conclusions: Fatigue is associated with an increase in HCU only in the setting of concomitantly active disease. On the other hand, fatigue is associated with a negative impact on WPAI in the setting of both active and inactive disease.

Background: Psychiatric disease burden in patients with Inflammatory bowel disease (IBD) has risen substantially over the past few decades. However, there is limited data on the relationship between IBD disease activity and the incidence of psychiatric comorbidities. We sought to conduct a population-based study to investigate the impact of early onset disease activity in newly diagnosed IBD patients on psychiatric disease diagnoses and medication usage.

Methods: We performed a retrospective cohort study using the TriNetX database. We identified all adult patients diagnosed with IBD and documented IBD-specific medication use. We stratified these IBD patients into 2 cohorts based on IBD Disease Activity, occurring 6 months to 1 year after initial IBD diagnosis. Active IBD was defined as the utilization of steroids and/or elevated fecal calprotectin [≥200 µg/g] occurring 6 months to 1 year after initial IBD diagnosis. We examined the outcomes of psychiatric disease diagnoses and psychotropic medication prescriptions occurring 1 year after the initial diagnosis.

Results: Out of 69 105 patients with an IBD diagnosis during the study period, after propensity score matching, 16 922 IBD patients each were included in the 2 cohorts based on disease activity. Patients with active IBD had significantly higher odds of developing major depressive disorder, anxiety disorder, bipolar disorder, alcohol use disorder, opiate use disorder, attention deficit hyperactivity disorder, and obsessive-compulsive disorder. Additionally, patients with active IBD also had significantly higher odds of using all studied psychotropic medications, including antidepressants, antipsychotic medications, anxiolytics, sedatives, hypnotic medications, mood stabilizers, stimulant medications, and medications used for substance use disorders (including alcohol, opioid, and tobacco use).

Conclusions: Active IBD shortly after the IBD diagnosis is associated with a higher incidence of psychiatric comorbidities. Awareness of behavioral health in IBD is important, and proper treatment is necessary.

Background/aims: Active inflammatory bowel disease (IBD) increases the risk of pregnancy complications and contraceptive side effects, and contraceptive use may impact the clinical course of IBD. Although young people are at elevated risk for unintended pregnancy, those with IBD receive minimal disease-specific contraceptive guidance. We characterized perspectives and preferences on contraception and reproductive health counseling from young cis-women with IBD.

Methods: We conducted 60-min semi-structured interviews with cis-women with IBD ages 18-30 (recruited nationwide and from North Carolina IBD clinics; February-June 2023). Interview guides included questions about reproductive health and preferences for receiving reproductive health information. Audio-recordings were professionally transcribed and coded using an inductive, thematic approach and Dedoose software.

Results: Participants included 30 cis-women with IBD (ages 18-30, 77% White, 7% Hispanic, and 55% Crohn's disease). Some participants shared that IBD increased their menstrual symptom burden, prompting contraceptive use to control menses. Participants discussed the impact of IBD on their contraceptive decision-making, including concerns regarding blood clots. For a participant subset, IBD did not impact contraceptive decision-making. Participants discussed how IBD impacted their perspectives on childbearing, including concerns about IBD heritability, infertility, and peripartum IBD flares. Participants wanted their gastroenterology provider to proactively address reproductive health, provide appropriate resources, and coordinate care with reproductive health providers.

Conclusions: Young cis-women with IBD may have IBD-specific concerns about contraceptives, pregnancy, and menstrual symptoms and desire better IBD-related reproductive health counseling. Inflammatory bowel disease providers can improve reproductive health counseling by proactively addressing IBD-specific reproductive health questions, providing reproductive health resources, and coordinating care.

Background: Despite advancements in the therapeutic armamentarium for Crohn's disease (CD), biologic and small molecule monotherapies are associated with sub-optimal response and remission rates. Utilizing dual biologic therapy (DBT) holds the potential to increase efficacy in the treatment of refractory or partially responsive CD. Evidence pertaining to this strategy remains limited.

Methods: We retrospectively examined refractory CD patients treated with a combination of ustekinumab and vedolizumab. Outcomes to DBT at week (wk) 52 were compared to monotherapy. The primary outcome constituted corticosteroid-free remission. Secondary outcomes included adverse events, infections, hospitalizations, surgeries, treatment persistence, and disease clearance.

Results: Sixteen of 21 active refractory CD patients (76%) on DBT achieved disease remission at wk 52. Mucosal healing was observed in 38% (n = 6), biochemical remission in 25% (n = 4), and both clinical and biochemical remission in 38% (n = 6). Of these patients, 50% (n = 8) achieved corticosteroid-free remission. Three patients (37.5%) with corticosteroid-free remission achieved complete disease clearance. Paired median fecal calprotectin decreased from 508 to 118 µg/g (P < .0001). Paired C-reactive protein median decreased from 1.04 to 0.50 mg/dL (P < .0001). Median Harvey Bradshaw Index score reduced from 7 to 2 (P = .003). Endoscopic healing was achieved with a paired simple endoscopic score for CD decrease from 6 to 3 (P = .013). Corticosteroid dependency reduced from 17 to 8 patients discontinuing altogether. Patients still requiring corticosteroids experienced a decrease in average daily dose from 9 to 6 mg (P = .045). At wk 52, 5 patients (24%) did not meet the criteria for remission with 4 requiring CD-related surgical intervention. Mean CD-related hospitalizations reduced from 2.95 ± 2.33 to 0.52 ± 1.12 (P < .001) and surgeries from 1.76 ± 1.3 to 0.14 ± 0.4 (P < .001). Three infections with 1 requiring hospitalization and 1 report of headache were noted. Two patients discontinued DBT.

Conclusions: Dual biologic therapy with ustekinumab and vedolizumab is a safe and effective strategy to induce disease remission in refractory CD. Large-scale studies are necessary to validate findings in a prospective setting.

Background: Exit interviews with patients who completed the Phase 3 VIVID-1 mirikizumab clinical trial for moderately-to-severely active Crohn's disease explored the content validity of bowel urgency, stool frequency, and abdominal pain patient-reported outcome measures and perceptions of meaningful within-patient change and remission in these key Crohn's disease symptoms.

Methodology: Cognitive debriefing explored patient understanding of the bowel urgency numeric rating scale (Urgency NRS), Crohn's Disease Activity Index: Stool Frequency (CDAI-SF) and Abdominal Pain (CDAI-AP), and patient global rating/impression of severity/change (PGRS/PGIC). Perceptions of meaningful change and remission were explored qualitatively. Transcripts were analyzed using directed content and framework analysis.

Results: Interviewed participants (N = 62; mean age 44.8 years, 55% female, mean 12.0 years since Crohn's disease diagnosis) were from the United States (n = 29), Czech Republic (n = 10), Poland (n = 8), Germany (n = 7), Canada (n = 4), Australia (n = 3), and the United Kingdom (n = 1). Participants understood the Urgency NRS, CDAI-SF, and CDAI-AP and could use them to rate their bowel urgency, stool frequency, and abdominal pain. Participants considered these symptoms when responding to the PGRS/PGIC. Meaningful change was described as symptom relief resulting in the ability to live daily life without pain or fear/need of rushing to the toilet. Most participants agreed with a proposed remission definition of ≤3 type 6/7 bowel movements and None/Mild abdominal pain.

Discussion: The Urgency NRS, CDAI-SF, and CDAI-AP are content-valid patient-reported outcome measures in Crohn's disease. The PGRS/PGIC are conceptually related global assessments of bowel urgency, stool frequency, and abdominal pain. Patients considered reduction in these symptoms as meaningful and remission.

Background: Medically refractory Crohn's disease (CD) is associated with a high risk of complications. Mycophenolate mofetil (MMF), a small molecule immunosuppressant, has limited data in patients with CD, and objective endoscopic response to MMF has not been reported.

Aims: We evaluated the safety and clinical, endoscopic, and biochemical effectiveness of off-label MMF for refractory CD as monotherapy or in combination with a biologic in patients with CD.

Methods: We retrospectively assessed adverse events (AEs), clinical response (Harvey-Bradshaw index), endoscopic response (simple endoscopic score in Crohn's disease), and physician global assessment at an academic medical center and county hospital.

Results: 60 patients received MMF as monotherapy (n = 40) or in combination with a biologic (n = 20) between 2008 and 2021 at a dose ranging from 1000 to 4000 mg daily. Median age was 39 years and median disease duration was 12 years. All patients previously failed ≥ 1 advanced therapy (median = 4). The median MMF therapy duration was 27 weeks. 54% achieved clinical response and 19% achieved clinical remission after a mean of 19.5 weeks (SD 14.5). Endoscopic response occurred in 32%, endoscopic remission in 16%, and endoscopic healing in 4% after a mean of 46.6 weeks (SD 31.0). 48% of patients experienced AEs, most commonly mild infection, nausea/vomiting, and headache. One serious AE occurred, which was assessed as unrelated to MMF.

Conclusions: MMF resulted in clinical, endoscopic, and biochemical benefits in some patients with refractory CD, and was tolerated by most patients. Further randomized controlled trials are needed to define optimal dosing and long-term efficacy and safety.

Background: This study aimed to describe the patient-reported factors that impact sleep among individuals with inflammatory bowel disease (IBD), aligning with the Social Ecological Model of Sleep. This addresses the gap in IBD sleep research, which predominantly focuses on individual-level factors and their impact on sleep.

Methods: Adults (ages 18-65) with IBD were recruited online through ResearchMatch in June 2023. Participants filled out survey questions on their demographic characteristics, health history, sleep, and IBD-related symptoms. Content analysis was conducted on 2 open-ended questions about factors that impacted their sleep.

Results: This analysis included 163 adults with IBD (M = 39 years of age, 76.7% White, 91.4% non-Hispanic or Latino, 66.9% female, and 83.4% active IBD) who answered open-ended questions with comments about their sleep. Most participants indicated an individual-level factor impacted their sleep quality (85.3%, n = 139), categorized into 5 subthemes: Mental health, health, behavior and choices, physiology, and attitudes. Additionally, participants (43.6%, n = 71) mentioned social-level factors divided into 7 subthemes: Family, work, home, neighborhood, social network, and school. A smaller group of participants (17.2%, n = 28) mentioned societal-level factors designated into 4 subthemes: Natural environment and geography, technology, 24/7 society, and economics.

Conclusions: This study highlights the need for tailored sleep interventions for those with IBD that consider not only disease activity but also mental health, family, work, and the natural environment. IBD clinics should prioritize sleep health using an interdisciplinary approach to holistically address the unique needs of those with IBD.

Background: Despite a wide range of available treatments, there is limited evidence as to why significant numbers of Crohn's disease (CD) patients do not achieve disease remission or continue to have residual symptom burden. We aimed to quantify the impact of this suboptimal treatment on patient symptom incidence and severity, quality of life (QoL), and work impairment.

Methods: Data were derived from the Adelphi Real World CD Disease Specific Programme, a cross-sectional survey of CD patients and their treating physicians in France, Germany, Italy, Spain, the United Kingdom, and the United States between January 2020 and March 2021. Physicians reported on patients' clinical history, disease status, symptom load, and treatment. Patients reported their QoL and activity impairment using the EQ-5D-5L and Work Productivity and Activity Impairment measures. Patients were divided into remitters, partial remitters, and non-remitters. Multivariate regression models were used to assess the impact of remission status on clinical and QoL outcomes.

Results: Of 1786 patients, 24.1% were remitters, 53.2% were partial remitters, and 22.7% were non-remitters. Partial remitters and non-remitters had a significantly higher symptom load than remitters (P < .05), and non-remitters were up to 15 times more likely to experience key symptoms than remitters. Both non-remitters and partial remitters were also significantly more likely to have increased symptom severity (P < .05). Non-remitters were more likely to have switched treatment and received more treatment lines, as well as having significantly worse QoL, than remitters.

Conclusions: Suboptimal treatment response was associated with increased symptoms and QoL burden. Despite the increased burden experienced, partial remitters were not more likely to switch or receive more treatment lines than remitters, demonstrating the need to initiate effective therapy.

Background/aims: The role of ustekinumab therapeutic drug monitoring in patients with Crohn's disease (CD) remains ambiguous. Examination of the association serum ustekinumab concentrations and endoscopic outcomes has yielded inconsistent results. Our study examined whether serum ustekinumab concentrations were associated with endoscopic healing in patients with moderate-to-severe CD.

Methods: This was a cross-sectional study of adult patients with CD on maintenance ustekinumab. Patients were included if they had serum ustekinumab concentrations and endoscopic evaluation taken within 4 months of each other. Endoscopic healing was defined as absence of ulceration on endoscopy or Simplified Endoscopic Score for Crohn's disease (SES-CD) < 3. Quartile analysis of drug levels was performed, and receiver operating characteristic curve was calculated. Multivariate logistic regression assessed for the probability of endoscopic healing based on serum ustekinumab concentration.

Results: Seventy-four patients were included in the final analysis. The mean serum ustekinumab concentration of the population was 6.10 mcg/mL. Serum ustekinumab concentration did not predict endoscopic remission based on either the absence of ulceration or SES-CD < 3. There was no difference in the frequency of ulceration at increasing serum ustekinumab concentrations. There was no threshold serum ustekinumab concentration associated with the absence of ulceration (area under the curve [AUC] = 0.50) or SES-CD < 3 (AUC = 0.49).

Conclusions: Our study found no association between serum ustekinumab concentrations and endoscopic remission in patients with CD. Exploration of mechanisms accounting for this lack of association is warranted.

Background: Ulcerative colitis (UC) is a prevalent inflammatory bowel disease primarily impacting the mucosa of the colon. It is characterized by recurring and incurable symptoms and causes immense suffering and significant economic burden due to limited treatment options. Typical symptoms of UC include diarrhea, alterations in bowel patterns, bleeding from the rectum, rectal pain or urgency, anemia, and tiredness. Therefore, developing novel and effective treatment strategies for UC is imperative.

Purpose: This review aimed to explain how macrophage polarization contributes to UC development and compiled information on natural compounds with promising therapeutic potential that can target the macrophage phenotype and shed light on its potential mode of action.

Results: The phenotypic alteration of macrophages profoundly affects the development of UC, and these cells are essential for preserving intestinal immunological homeostasis. Evidence from research suggests that one effective method for UC prevention and therapy is to guide macrophage polarization toward the M2 phenotype. Phytochemicals, which are compounds extracted from plants, possess a wide array of biological activities. For example: Ginsenoside Rg1 emerges as a crucial regulator of macrophage polarization, promoting the M2 phenotype while inhibiting the M1 phenotype. Notably, their low toxicity and high effectiveness render them promising candidates for therapeutic interventions. These compounds have demonstrated encouraging protective effects against inflammation in the colon.

Conclusions: Exploring phytochemicals as a therapeutic avenue targeting macrophage polarization presents an innovative approach to treating UC.