Crohn's & Colitis 360最新文献

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.

Background: Isolated complex perianal fistulas, without luminal evidence of inflammatory bowel disease in the gastrointestinal tract, pose diagnostic and treatment dilemmas for gastroenterologists and colorectal surgeons. For patients who develop recurrent complex fistulas, a presumptive diagnosis of Crohn's disease may be made. It is unclear whether these cases of isolated perianal disease in the absence of luminal inflammation truly represent isolated severe cryptoglandular fistulas or rather an early presentation of Crohn's disease. We aimed to investigate the clinical course and outcomes of patients with isolated complex perianal fistulas.

Methods: In this retrospective multicenter case series across 6 institutions in the United States, we report the clinical course of patients with isolated recurrent complex perianal fistulas, including their diagnostic evaluation, medical and surgical therapies, and clinical outcomes.

Results: All patients (n = 24) required incision and drainage of perirectal abscesses. The majority received setons (n = 19, 79%), more intensive surgical interventions (n = 15, 62.5%, including fistulotomy/sphincterotomy, advancement flap, and ligation of the intersphincteric fistula tract), antibiotics (n = 17, 71%), and biologic therapy (n = 16, 67%). Nine patients (37.5%) underwent a combined medical-surgical approach with biologics and intensive surgical intervention. Despite surgical and/or medical management, active symptomatic complex perianal fistulas persisted in 58% (n = 14) of patients at follow-up (median 5.5 years, interquartile range 2.5-10 years); symptom remission was achieved in 21% (n = 5), and fistula closure in 21% (n = 5).

Conclusions: These cases highlight a multidisciplinary and multimodal approach when treating isolated complex perianal fistulas and their propensity to persist despite the incorporation of advanced therapies.

As biosimilars become more available, many patients with inflammatory bowel disease may experience having their treatment switched from a reference product to a biosimilar. In this communication, a physician assistant and a pharmacist discuss the patient experience when switching to a biosimilar.

Background: No models predict future outcomes in inflammatory bowel disease (IBD) patients receiving maintenance infliximab therapy. We created a predictive model for unfavorable outcomes.

Methods: Adult patients with IBD receiving maintenance infliximab therapy at 2 centers with matched serum infliximab concentrations and blinded histologic scores (Robarts Histopathologic Index [RHI]) were included. The primary endpoint was an unfavorable outcome of active objective inflammation or need for IBD-related surgery or hospitalization at 6-18 months follow-up. Internal variables were identified using univariable analyses, modeling used multivariable analysis, and performance was assessed (area under receiver-operating curve [AUC]) and externally validated.

Results: In 81 patients, 40.7% developed unfavorable outcomes at follow-up. Infliximab concentration <9.3 µg/mL (odds ratio [OR] 5.3, P = .001) and RHI > 12 (OR 3.4, P = .03) were the only factors associated with developing the primary unfavorable outcome. A prediction score assigning 1 point to each variable had good discrimination and performed similarly on internal (AUC 0.71) and external (AUC 0.73) cohorts. The risk of primary unfavorable outcomes in internal and external cohorts, respectively, was 23% and 15% for a score of 0, 46% and 50% for a score of 1, and 100% and 75% for a score of 2. Infliximab concentration alone performed similar to the 2-predictor model in internal (AUC 0.65, P = .5 vs. 2-predictor model) and external (AUC 0.70, P = .9, vs. 2-predictor model) cohorts.

Conclusions: Using unbiased variable selection, a 2-predictor model using infliximab concentrations and histology identified IBD patients on maintenance infliximab therapy at high risk of future unfavorable outcomes. For practical applicability, infliximab concentrations alone performed similarly well.

Background: Crohn's disease (CD) presents with diverse phenotypes. It remains unclear if CD location affects therapy efficacy. The aim of this study was to compare the real-world performance of ustekinumab in ileum-dominant and colonic CD.

Methods: We performed a single-center, IRB-approved, retrospective review of all adult CD patients who received ustekinumab. We stratified patients by ileal involvement: ileum-dominant (ileal and ileocolonic) and colonic CD. The primary outcome was the absence of ulcers on follow-up colonoscopy. The secondary outcomes included CRP, calprotectin, surgery, and hospitalization. Chi-square tests (or Fisher's exact test) and 2-sample t-tests (or Wilcoxon's rank-sum test) were used to compare categorical and numeric variables between groups, respectively; analyses were performed using R Computing Software versions 3.6.1.

Results: Eighty-four patients with ileum-dominant CD and 27 patients with colonic CD were treated with ustekinumab. The median time to follow-up endoscopy was 13 months. Follow-up colonoscopy after ustekinumab therapy was ulcer-free in 45% of ileum-dominant CD and 76% of colonic CD (P = .02). Of patients with ulcers prior to starting ustekinumab, 24% of ileum-dominant CD and 67% of colonic CD were ulcer-free (P = .01). There were similar rates of hospitalizations and surgery and no significant differences in mean calprotectin and CRP between the two groups on follow-up after ustekinumab therapy.

Conclusions: This real-world experience of ustekinumab demonstrates higher rates of endoscopic healing among colonic CD when compared to ileum-dominant CD. Disease location may predict endoscopic healing by ustekinumab. Further studies are necessary to expand our understanding of ustekinumab responsiveness to different CD phenotypes.

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), often results in significant morbidity among patients with moderate to severe forms. While biologics and small molecules are effective in inducing remission, many patients experience refractory disease or extraintestinal manifestations. This study assesses the safety and efficacy of dual-targeted therapy in IBD patients treated at the Inflammatory Bowel Disease Center.

Methods: This retrospective cohort study examined 79 patients with UC or CD who received dual-targeted therapy at the University from October 2018 to August 2023. Data collected included demographics, disease characteristics, previous treatments, and clinical outcomes. Primary outcomes were endoscopic, radiographic, and patient-reported clinical improvements, with secondary outcomes focusing on safety profiles.

Results: Among the 79 patients (42 UC, 37 CD), 97 dual-targeted therapy cases were analyzed, primarily involving a biologic combined with a JAK inhibitor (90.7%). The median therapy duration was 39.1 weeks. Endoscopic improvement occurred in 69% of matched samples, with significant differences between pre- and postdual-targeted therapy Mayo scores for UC (P = .002) and Simple Endoscopic Score for CD (SES-CD) scores for CD (P = .018). The median pre- and postdual-targeted therapy Mayo scores across matched samples were 3 (range 1-3) and 1 (range 0-3), respectively, and for SES-CD scores were 12 (range 0-36) and 4 (range 0-20), respectively. Clinical improvement was reported by 73.2% of patients, with notable reductions in ESR (median 19 [range 2-124] mm/h to 9 [range 0-116] mm/h, P = .006), CRP (median 8.0 [range 0.2-78.5] mg/L to 3.0 [range 0.2-68.2] mg/L, P < .001), and albumin levels (4.0 [range 2.2-4.9] mg/dL to 4.2 [range 3.4-5.2], P < .001). Non-obesity was associated with both more endoscopic improvement (P = .002) and clinical improvement (P = .007). Adverse events occurred in 37 cases, predominantly upper respiratory tract infections and dermatologic issues, with no thromboembolic events reported.

Conclusions: Dual-targeted therapy demonstrated efficacy in improving clinical and endoscopic outcomes in patients with severe, refractory IBD and exhibited an acceptable safety profile. Despite the promising results, further research is needed to confirm these findings and determine optimal therapy combinations.

Background: Antitumor necrosis factor (anti-TNF) biologics have revolutionized the treatment of inflammatory bowel disease (IBD). Previously, studies have shown an association between the HLADQA1*05 allele and the development of antibodies and were predictive of loss of response. We sought to investigate the rate of the HLADQA1*05 allele in patients with IBD at a New England center and its association with antibody development and discontinuation of anti-TNF therapy.

Methods: A single center retrospective cohort study with patients on anti-TNF inhibitor therapy being followed at our IBD clinic who had testing performed for the HLADQA1*05 allele were identified and separated into 2 different groups: HLADQA1*05 positive (HLA carriers) or HLADQA1*05 negative (HLA noncarriers). Persistence of remaining on anti-TNF therapy, measurement of drug/antibody levels, and need for dose escalation were collected and stratified amongst the 2 groups.

Results: The prevalence of the HLADQA1*05 allele among all IBD patients followed was 53%. We identified 67 IBD patients being treated with anti-TNF medications, 46 (69%) patients with Crohn's disease and 21 (31%) with ulcerative colitis. Most of the HLA carriers (85%) and HLA noncarriers (92%) remained on anti-TNF therapy at the end of the study period. Thirty-six (84%) patients had therapeutic drug monitoring performed during maintenance therapy. Three patients in the HLA carrier group had meaningful antidrug antibody levels necessitating cessation of therapy compared to one patient in the HLA noncarrier group (P = .61). Only 3 (13%) of HLA carriers and 4 (21%) of HLA noncarriers were on combination therapy with an immunomodulator. 65% of HLA carriers required dose escalation compared to 50% of HLA noncarriers (P = .70).

Conclusions: The prevalence of the HLADQA1*05 allele was 53% in our New England IBD patient population, similar to what has previously been reported in European studies. The majority of patients remained on anti-TNF therapy at the end of the study period despite carrier status. While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.

Background: Patients with ulcerative colitis (UC) typically receive a targeted inflammatory bowel disease therapy after treatment with conventional therapies and after the development of significant morbidity. Evidence suggests that early biologic treatment after diagnosis could improve treatment response and prevent disease complications compared with delayed biologic treatment after conventional therapy.

Methods: RALEE was a retrospective study using claims data from IBM® MarketScan® Research Databases between January 1, 2016 and December 31, 2019. Adults with UC and at least one claim for vedolizumab were categorized into Early or Delayed Vedolizumab groups according to whether they had received vedolizumab within 30 days of diagnosis or after conventional therapy (5-aminosalicylates, corticosteroids, and immunomodulators), respectively. Treatment response was assessed at 2, 6, and 12 months after vedolizumab treatment initiation and was analyzed with logistic regression (bivariate).

Results: At 2 months, Delayed Vedolizumab was associated with significantly higher odds of nonresponse than Early Vedolizumab (odds ratio [OR], 2.509; 95% confidence interval [CI], 1.28-4.90). Delayed Vedolizumab was not significantly associated with odds of nonresponse at 6 months (OR, 1.173; 95% CI, 0.72-1.90) or at 12 months (OR, 0.872; 95% CI, 0.55-1.37). Mean total healthcare costs were similar in the Early Vedolizumab ($6492) and Delayed Vedolizumab ($5897) groups, although there were small differences in costs from different types of claims.

Conclusions: Patients who received vedolizumab early after UC diagnosis were less likely to experience nonresponse at 2 months and incurred similar healthcare costs at 12 months compared with patients who received delayed vedolizumab.

Background: Ulcerative colitis (UC), a chronic inflammatory bowel disease, causes stomach pain, diarrhea, and rectal bleeding. The exact cause is unknown, but it is thought to involve genetic, environmental, and psychological factors. Some people experience annual flare-ups without obvious reason. This article adopts a theory-driven approach to consider how and why past traumatic events may contribute to annual flare-ups.

Methods: We applied learning theory, which explains the development of re-experiencing phenomena in post-traumatic stress disorder (PTSD), to better understand the occurrence of annual flares in patients living with UC.

Results: Two possibilities emerged in which associative learning may contribute to annual UC flares. First, flare-ups could be a physical response to sensory cues in the present that overlap with trauma experienced at the first onset of UC. Annual episodes may strengthen the UC flare as a learned physiological response to trauma reminders. Second, flare-ups may result from elevated stress due to trauma re-experiencing at anniversaries. Sensory features of the initial UC trauma may be associated with strong reactions, which generalize to similar stimuli, triggering re-experiencing symptoms and increasing psychological stress. Elevated stress raises glucocorticoid levels, promoting UC-specific inflammation. Stimulus discrimination from cognitive therapy for PTSD may help to over-ride the associations that have formed between sensory features of past trauma, linked reactions, and similar cues in the present.

Conclusions: Research is needed to understand how traumatic events influence the onset and recurrence of ulcerative colitis, as well as the potential benefits of stimulus discrimination for reducing the frequency of annual flares.