Partial Mayo Score Research Articles

Comparison of the Gut Microbiota of Patients Who Improve with Antibiotic Combination Therapy for Ulcerative Colitis and Those Who Do Not: Investigation by Fecal Metagenomic Analyses.

Background/Objectives: The cause of ulcerative colitis (UC) may be related to commensal bacteria in genetically susceptible patients. We previously demonstrated that triple antibiotic combination therapy induces remission in patients with active UC in randomized controlled trials (RCTs). Now, we investigate changes in the gut microbiota of patients who responded to the antibiotic combination therapy. Methods: Thirty-one patients with UC given ATM/AFM (amoxicillin, metronidazole, and tetracycline or fosfomycin) therapy for two weeks were enrolled in this study. The clinical conditions of these UC patients were evaluated by the partial Mayo score. The gut microbiota was compared via the metagenomic shot gun analysis of fecal samples. Results: Of the 31 patients, 16 and 8 experienced complete and partial remission, respectively, over three months in response to ATM/AFM therapy, whereas ATM/AFM showed no efficacy in 7 patients. The dysbiosis before treatment in the active stage could be associated with increased populations of Bacteroides, Parabacteroides, Rickenella, Clostridium, Flavonifractor, Pelagibacter, Bordetella, Massilia, and Piscrickettsia species. Metagenomic analysis revealed dramatic changes in the gut microbiota at an early stage, that is, just two weeks after starting ATM/AFM therapy. After treatment in the responder group, the populations of bifidobacterium and lactobacilli species were significantly increased, while the population of bacteroides decreased. Conclusions: These results suggest that metagenomic analysis demonstrated a marked change in the gut microbiota after antibiotic combination treatment. In the triple antibiotic combination therapy, remission was associated with an increase in bifidobacterium and lactobacilli species.

Low-Grade Activation of the Extrinsic Coagulation Pathway in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP). To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC). In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated. UC patients had 4- and 3.7-times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (-0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (-0.64), albumin (-0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2-times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (-0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05. Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.

Model-Informed Assessment of Probability of Phase 3 Success for Ritlecitinib in Patients with Moderate-to-Severe Ulcerative Colitis.

Ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family inhibitor, was evaluated in patients with ulcerative colitis (UC) in a phase 2b trial. Model-informed drug development strategies were applied to bridge observations from phase 2b to predictions for a proposed phase 3 study design to assess the probability of achieving the target efficacy outcome. A longitudinal exposure-response model of the time course of the 4 Mayo subscores (rectal bleeding, stool frequency, physician's global assessment, and endoscopic subscore) in patients with UC receiving placebo or ritlecitinib was developed using population modeling approaches and an item response theory framework. The quantitative relationships between the 4 Mayo subscores accommodated the prediction of composite endpoints such as total Mayo score and partial Mayo score (key endpoints from phase 2b), and modified clinical remission and endoscopic remission (proposed phase 3 endpoints). Clinical trial simulations using the final model assessed the probability of candidate ritlecitinib dosing regimens (including those tested in phase 2b and alternative) and phase 3 study designs for achieving target efficacy outcomes benchmarked against an approved treatment for moderate-to-severe UC. The probabilities of achieving target modified clinical remission and endoscopic improvement outcomes at both weeks 8 and 52 for ritlecitinib 100 mg once daily was 74.8%. Model-based assessment mitigated some of the risk associated with proceeding to pivotal phase 3 trials with dosing regimens of which there was limited clinical experience.

A diagnostic dilemma: cytomegalovirus colitis as an uncommon comorbidity in inflammatory bowel disease: a case report

BackgroundThe role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy.Case presentationA 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed.ConclusionConcurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.

Absence of Paneth Cell Metaplasia to Predict Clinical Relapse in Ulcerative Colitis with Endoscopically Quiescent Mucosa.

Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP). Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated. Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03). The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing.

Combination of granulocyte–monocyte apheresis and tofacitinib: Multicentre and retrospective study

ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. Patients and methodsRetrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. ResultsTwelve patients were included (median 46 years [IQR, 37–58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5–7), and it decreased to a median of 2 (IQR, 0–3) and 0 (IQR, 0–3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. ConclusionThe combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug.

Long-Term Outcomes of Intravenous Ustekinumab Maintenance Treatment in Patients With Loss of Response to Subcutaneous Dosing.

Ustekinumab (UST) is commonly used to treat Crohn's disease and ulcerative colitis. However, some patients may experience diminishing response or require increased dosage. Intravenous (IV) UST maintenance is explored as a solution. We sought to evaluate IV UST maintenance effectiveness and safety in inflammatory bowel disease patients with partial or lost subcutaneous UST response. This was a multicenter retrospective study of inflammatory bowel disease patients on IV UST maintenance. Clinical response and remission at weeks 12 and 52, defined as Harvey-Bradshaw Index ≤4 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis. Objective markers reduction (fecal calprotectin, C-reactive protein), UST trough levels pre- and post-IV maintenance, and adverse events were assessed. A total of 59 patients were included. Clinical remission at weeks 12 and 52 achieved by 47.5% and 64.3% respectively. 96.6% continued IV UST at follow-up. UST serum levels quadrupled. No adverse events reported. IV UST maintenance effectively sustained remission in most patients at 52 weeks.

Switching from Dose-Intensified intravenous to SubCutaneoUS infliximab in Inflammatory Bowel Disease (DISCUS-IBD): protocol for a multicentre randomised controlled trial

IntroductionA substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement....

Real-life effectiveness and safety of vedolizumab in moderate-to-severe ulcerative colitis: A single-center experience in Northern China.

Vedolizumab (VDZ), a monoclonal antibody to α4β7 integrin, is available for patients with moderate-to-severe ulcerative colitis (UC). This study planned to assess the real-world effectiveness and safety of VDZ for UC patients in Northern China. We enrolled patients with moderate-to-severe UC who underwent VDZ induction therapy from March 2021 to November 2022 at the Affiliated Hospital of Qingdao University. The primary outcome was clinical remission at weeks 14 and 52 after the initial VDZ therapy. Overall adverse events and risk factors associated with loss of response (LOR) were also evaluated. Seventy-three UC patients receiving VDZ therapy were included in this study. The rates of clinical response, clinical remission, and steroid-free clinical remission were 69.9%, 39.7%, and 34.2% at week 14 and 90.5%, 66.7%, and 64.4% at week 52, respectively. The mucosal remission rates were 37.5% (18/48) at week 14 ± 8 and 27.3% (9/33) at week 52 ± 16, while only 2 and 3 patients achieved mucosal healing at weeks 14 ± 8 and 52 ± 16, respectively. Of the UC patients, 23.3% experienced adverse events associated with VDZ, most of which were mild and self-limiting. Until the last follow-up, 37 of 73 UC patients experienced LOR during the maintenance period. Patients with a higher ulcerative colitis endoscopic severity index (UCEIS), partial Mayo scores (PMS), or hemoglobin below 120 g/L at baseline were more likely to experience LOR after VDZ induction therapy. VDZ is an effective and safe agent for patients with moderate-to-severe UC in Northern China. A high baseline UCEIS, PMS, or hemoglobin < 120 g/L may be an independent risk factor for LOR during the maintenance period.

Automated Neutrophil Quantification and Histological Score Estimation in Ulcerative Colitis

Background and AimsIn the management of ulcerative colitis (UC), histological remission is increasingly recognized as the ultimate goal. The absence of neutrophil infiltration is crucial for assessing remission. This study aimed to develop an artificial intelligence (AI) system capable of accurately quantifying and localizing neutrophils in UC biopsy specimens to facilitate histological assessment. MethodsOur AI system, which incorporates semantic segmentation and object detection models, was developed to identify neutrophils in hematoxylin-eosin-stained whole slide images. The system assessed the presence and location of neutrophils within either the epithelium or lamina propria and predicted components of the Nancy Histological Index (NHI) and the PICaSSO Histologic Remission Index (PHRI). We evaluated the system’s performance against that of experienced pathologists and validated its ability to predict future clinical relapse risk in patients with clinically remitted UC. The primary outcome measure was the clinical relapse rate, defined as a partial Mayo score of ≥3. ResultsThe model accurately identified neutrophils, achieving a performance of 0.77, 0.81, and 0.79 for precision, recall, and F-score, respectively. The system’s histological score predictions showed a positive correlation with the pathologists’ diagnoses (Spearman’s ρ = 0.68–0.80, P < .05). Among patients who relapsed, the mean number of neutrophils in the rectum was higher than in those who did not relapse. Furthermore, the study highlighted that higher AI-based PHRI and NHI scores were associated with hazard ratios increasing from 3.2 to 5.0 for evaluating the risk of UC relapse. ConclusionThe AI system’s precise localization and quantification of neutrophils proved valuable for histological assessment and clinical prognosis stratification.

Early Intestinal Ultrasound in Severe Ulcerative Colitis Identifies Patients at Increased Risk of 1-Year Treatment Failure and Colectomy

Abstract Background and Aims Reliable and easily accessible objective markers of disease activity to predict long-term treatment outcomes in severe ulcerative colitis [UC] are missing. We aimed to investigate if intestinal ultrasound [IUS] might predict long-term outcomes in hospitalised patients with severe UC, treated with intravenous [IV] corticosteroids. Methods Hospitalised patients with severe UC and IUS inflammation (bowel wall thickness [BWT] &amp;gt; 3.0 mm) starting IV corticosteroids were recruited at three university hospitals in Denmark. IUS was performed before treatment and 48 ± 24 h, 6 ± 1 days, and 3 months after treatment initiation. Time until colectomy or need for new interventions was registered together with Mayo score at 3 months and partial Mayo score [pMayo] at 12 months. Follow-up time was 12 months. Results In the final analysis, 56 patients were included; 45 [80%] patients needed intervention, including nine colectomies, during the 12-month follow-up. After 48 ± 24 h, no patient with a BWT &amp;lt; 3 mm needed a colectomy, p = 0.04. BWT ≥ 4 mm showed an increased risk of colectomy {odds ratio 9.5 (95% confidence interval [CI] 1.5–186), p = 0.03}, whereas a BWT ≥ 3 mm showed an increased risk of intervention (3.6 [1.1–12.5], p = 0.03). A BWT ≥ 4 mm resulted in a significantly shorter time until both colectomy, p = 0.03, and treatment intensification (mean days 75 [95% CI 24–127] vs 176 [119–233], p = 0.005). However, neither IUS parameters nor pMayo score, C-reactive protein [CRP], haemoglobin, or p-albumin could predict remission at 3 and 12 months. Conclusion BWT, assessed at 48 h post intravenous corticosteroid initiation in patients hospitalised with severe UC, may identify patients with an increased risk of short- and long-term colectomy and predict a more aggressive short-term disease course.

Fecal and Serum Granulocyte Protein Levels in Inflammatory Bowel Disease and Irritable Bowel Syndrome and Their Relation to Disease Activity.

Neutrophilic calprotectin (CP) and myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and eosinophil-derived neurotoxin (EDN) are suggested proxy markers for gut inflammation. However, there are insufficient supporting data for MPO, NGAL, and EDN. In a cross-sectional investigation including adult patients, we studied the ability of CP, MPO, NGAL, and EDN, measured in fecal and serum samples, to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and to predict disease activity. Fifty-nine patients had ulcerative colitis (UC), 38 had Crohn's disease, and 100 patients had IBS. The protein concentrations were higher in patients with IBD in the fecal samples ( P < 0.001) and the serum samples ( P < 0.01), and they correlated weakly (r s ≤0.38) between the sample sources. Fecal EDN was higher in patients with Crohn's disease compared with UC (1.79 vs 0.50 mg/kg, P = 0.016). The neutrophilic proteins were superior to EDN in the fecal samples for differentiating between patients with IBD and IBS. Fecal MPO (cutoff: 0.86 mg/kg) had the highest sensitivity (74.7%) and specificity (84.6%). Combining fecal CP and MPO increased the sensitivity to 82.3% (specificity: 73.6%). NGAL (cutoff: 196.9 μg/L) showed the best discriminating performance in serum (sensitivity: 62.9%; specificity: 68.0%). Serum NGAL (cutoff: 272.4 μg/L) predicted active disease in UC (Partial Mayo Score ≥2) with a sensitivity and specificity of 57.1% and 83.3%, respectively. Fecal MPO and serum NGAL are promising novel biomarkers, in addition to fecal CP, for differentiating between IBD and IBS. Serum NGAL may also predict disease activity in patients with UC.

Repurposing metformin as adjuvant therapy in patients with ulcerative colitis treated with mesalamine: A randomized controlled double-blinded study

BackgroundUlcerative colitis (UC) is a type of inflammatory bowel disease associated with persistent inflammation. Animal studies proved the efficacy of metformin in UC. AimTo investigate the potential role of metformin and its protective pathways in patients with UC. MethodsThis is a randomized, controlled, and double-blinded clinical trial that included 60 participants with mild to moderate UC and was divided randomly into two groups (n = 30). For 6 months, the mesalamine group received 1 g of mesalamine three times daily (t.i.d.). For six months, the metformin group received mesalamine 1 g t.i.d. and metformin 500 mg twice daily. A gastroenterologist evaluated patients at baseline and 6 months after starting the treatment in order to measure serum levels of zonulin, sphingosine 1 phosphate (S1P), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Biopsies from the colon were used to measure gene expression of zonula occuldin-1 (ZO-1), signal transducer and activator of factor-3 (STAT-3), and intracellular adhesion molecule-1 (ICAM-1). The numeric pain rating scale (NRS) and partial Mayo score were also assessed for each patient. ResultsWhen compared to the mesalamine group, the metformin group demonstrated a statistical decrease in serum IL-6, zonulin, TNF-α, SIP, gene expression of ICAM-1 and STAT-3, and a significant increase in colonic ZO-1 when compared to the mesalamine group. The metformin group also showed a significant decrease in NRS and partial Mayo score index in comparison with the mesalamine group. ConclusionMetformin may be a promising additional therapy for UC patients.Trial registration identifier: NCT05553704.

Effectiveness of Switching to Subcutaneous Infliximab in Ulcerative Colitis Patients Experiencing Intravenous Infliximab Failure.

Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment. This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC. Twenty-three patients met the inclusion criteria: 15 in group A and eight in group B. The serum infliximab levels significantly increased after SC switching in both groups. The electively switched group also exhibited increased infliximab levels after SC switching. Patients in group A showed improved partial Mayo score with a significant decrease in fecal calprotectin and C-reactive protein after switching. In group B, the fecal calprotectin level significantly decreased without clinical relapse after switching. A high proportion of patients (≥80%) in both groups achieved clinical and/or biochemical responses at the last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction. In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of better efficacy and safety.

Artificial intelligence-assisted video colonoscopy for disease monitoring of ulcerative colitis: A prospective study.

The Mayo endoscopic subscore (MES) is the most popular endoscopic disease activity measure of ulcerative colitis (UC). Artificial intelligence (AI)-assisted colonoscopy is expected to reduce diagnostic variability among endoscopists. However, no study has been conducted to ascertain whether AI-based MES assignments can help predict clinical relapse, nor has AI been verified to improve the diagnostic performance of non-specialists. This open-label, prospective cohort study enrolled 110 patients with UC in clinical remission. The AI algorithm was developed using 74713 images from 898 patients who underwent colonoscopy at three centers. Patients were followed up after colonoscopy for 12 months, and clinical relapse was defined as a partial Mayo score >2. A multi-video, multi-reader analysis involving 124 videos was conducted to determine whether the AI system reduced the diagnostic variability among six non-specialists. The clinical relapse rate for patients with AI-based MES = 1 (24.5% [12/49]) was significantly higher (log-rank test, P = 0.01) than that for patients with AI-based MES = 0 (3.2% [1/31]). Relapse occurred during the 12-month follow-up period in 16.2% (13/80) of patients with AI-based MES = 0 or 1 and 50.0% (10/20) of those with AI-based MES = 2 or 3 (log-rank test, P = 0.03). Using AI resulted in better inter- and intra-observer reproducibility than endoscopists alone. Colonoscopy using the AI-based MES system can stratify the risk of clinical relapse in patients with UC and improve the diagnostic performance of non-specialists.

Real-World Data on the Effectiveness and Safety of Filgotinib for Ulcerative Colitis in Japanese Patients: A Single-Center Experience.

Introduction Filgotinib is a JAK-1 selective inhibitor approved for ulcerative colitis (UC) treatment in Japan. Its effectiveness has been confirmed but remains unknown in actual clinical practice. Therefore, we aimed to evaluate the effectiveness and safety of filgotinib and identify suitable patients in the Japanese population. Methods We retrospectively reviewed the background, clinical course, and laboratory data of patients treated with filgotinib 200 mg for UC between May 2022 and December 2023. Results The median observation period for the 25 patients was 232 days (interquartile ranges (IQR) 102-405). The median age of the patients was 43 years (IQR 29-55), disease duration was nine years (IQR 2-12), and 36% (9/25) of patients were biologic or small molecule naïve. The median patient-reported outcome (PRO2) and partial Mayo (pMayo) scores at agent initiation were 3 (IQR 1-4) and 4.5 (IQR 3-6), respectively. The PRO2 and pMayo scores improved significantly two weeks after treatment initiation (p < 0.05). Clinical remission rates at 24 weeks after treatment initiation were 60% (15/25) for PRO2 ≤ 1 and 52% (13/25) for pMayo ≤ 1. The Mayo endoscopic subscoresignificantly improved after filgotinib initiation (p=0.04), and the endoscopic remission rate was 47% (8/17). At 24 weeks, patients in clinical remission, compared to those not in remission, had significantly lower baseline PRO2 and pMayo scores and longer disease duration (p=0.03, p=0.03, and p=0.04, respectively). The filgotinib persistence rate was 68% (17/25), with no discontinuation because of adverse events. Patients who continued treatment had significantly lower PRO2, pMayo scores, and blood neutrophil counts at initiation than those who discontinued (p=0.02, p=0.03, and p=0.02, respectively). Conclusion Filgotinib appears to be effective and safe in Japanese patients with UC. Effectiveness and persistence were high in patients whose PRO2 and pMayo scores were low at the time of treatment initiation.

Severe Disease Activity May Predispose Patients to Post-colectomy Duodenitis Associated with Ulcerative Colitis.

Objective Diffuse mucosal inflammation in the duodenum, distinct from peptic ulcer disease, has been repeatedly reported in patients with ulcerative colitis (UC). The pathogenesis of this complication remains uncertain; however, colectomy for medically refractory UC appears to trigger duodenitis. Cases in which colectomy was performed for UC were analyzed to characterize UC-related duodenitis after colectomy. Methods A retrospective case-control study of UC-related duodenitis that developed after colectomy in medically refractory UC between January 2011 and June 2020 was conducted. UC-related duodenitis was diagnosed based on typical clinical, endoscopic, and histological findings, and no duodenitis was endoscopically defined by the normal duodenal mucosa. Clinical and laboratory data, disease severity, and medications used were collected and compared between the UC-related and non-duodenitis cases. Results Ten UC-related duodenitis and 35 non-duodenitis cases were identified among 45 patients with UC who underwent esophagogastroduodenoscopy after colectomy. Disease severity, defined by the C-reactive protein level and partial Mayo score prior to colectomy, was significantly higher in duodenitis patients than in non-duodenitis patients. In comparison to non-duodenitis patients, duodenitis patients more frequently received rescue therapies with calcineurin inhibitors or anti-TNF-α agents at the time of colectomy (100% vs. 65.7%). Conclusion Patients with UC with higher disease activity, especially those who require rescue therapies with calcineurin inhibitors and anti-TNF-α agents, may be prone to developing UC-related duodenitis after colectomy.

Real-World Comparison of the Effectiveness between Ustekinumab and Vedolizumab in Patients with Ulcerative Colitis Exposed to at least One Anti-TNF Agent.

Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking. We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients. In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]. Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39-3.13], p = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [p = 0.52], 44.4% vs 33.8% [p = 0.52], and 2.6% vs 19.1% [p = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11-0.82], p = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab. While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.

Resolution of rectal bleeding by day 7 in acute severe ulcerative colitis is prognostic for post-discharge corticosteroid free clinical remission and endoscopic improvement.

This study assesses two different disease activity measures, the MTWSI and the partial Mayo score, in hospitalized acute severe UC patients for prediction of post-discharge corticosteroid-free clinical remission and endoscopic improvement to help guide future considerations for disease activity assessment. In this post-hoc analysis from the TRIUMPH trial, these results suggest resolution of Mayo rectal bleeding sub-score may have high prognostic utility and could be considered as a primary endpoint for hospitalized UC trials. The study underscores the need for further research on patient-reported outcomes and endoscopic indices in larger populations for inpatient UC trials.

Combination of granulocyte–monocyte apheresis and ustekinumab: Multicentre and retrospective study

ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. Patients and methodsA retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. ResultsSeventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35–61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5–7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. ConclusionGMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.