Introduction

A previous meta-analysis in Crohn’s disease (CD) patients suggested lower discontinuation rates due to lack of efficacy in infliximab (IFX) compared to vedolizumab (VDZ) during a one-year maintenance phase.¹ This study aims to compare the discontinuation rates due to lack of efficacy between VDZ and IFX by adding the one-year clinical results of "A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of the Subcutaneous Injection of CT-P13 (CT-P13 SC) as Maintenance Therapy in Patients With Moderately to Severely Active Crohn's Disease (LIBERTY-CD; NCT03945019)".²

Aims & Methods

Discontinuation rates due to lack of efficacy during the one-year maintenance phase were compared between the treatments. Using a random-effect model, pooled discontinuation rates were reported as forest plots with 95% confidence intervals (CI). The heterogeneity between studies was examined. A sensitivity analysis was conducted among patients who responded to induction therapy. Statistical analyses were performed using MetaProp in R (version 4.2.2).

Results

Four randomized controlled trials (RCTs) (NCT02883452, NOR-SWITCH, PLANETCD, and LIBERTY-CD) on IFX and two RCTs (GEMINI 2 and VISIBLE 2) on VDZ in patients with CD were included for the analysis (IFX: N=659, VDZ: N=995). Pooled discontinuation rates due to lack of efficacy during the one-year maintenance phase were significantly lower in patients who were treated with IFX (0.05 [95%CI: 0.00-0.09], heterogeneity: I²=86%) compared to those treated with VDZ (0.37 [95%CI: 0.26-0.48], heterogeneity: I²=93%) (Table 1). A sensitivity analysis was performed after excluding non-responders to induction therapy which resulted in slightly lower rates of discontinuation due to lack of efficacy in VDZ (0.32 [95% CI: 0.27-0.37], heterogeneity: I²=48%). However, the significant difference was maintained (Table 1).

Table 1. Discontinuation rates due to lack of efficacy during the one-year maintenance phase

Conclusion

Consistent with previous findings, IFX showed significantly lower rates of discontinuation due to lack of efficacy during the one-year maintenance compared to VDZ. In the sensitivity analysis that excluded non-responders to induction therapy in VDZ studies, the significant difference between treatments was maintained.

References

1. Ferrante M et al., A comparative analysis between infliximab and vedolizumab on patients with Crohn’s diseases and ulcerative colitis who discontinued during maintenance treatment due to lack of efficacy: Meta-analysis using randomized controlled trials. DDW 2022. Poster presentation.
2. Colombel J F et al., Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (LIBERTY-CD). Journal of Crohn’s and Colitis. 2023;17(Supplement_1):i161-i162. ECCO 2023, Presentation number DOP86.

Introduction

Non-invasive biomarkers are needed to improve the management of eosinophilic esophagitis (EoE). We investigated whether eosinophil and lymphocyte counts could be used to diagnose EoE among patients with dysphagia and assess histological, endoscopic, and clinical disease activity in patients with known EoE.

Aims & Methods

This was a prospective study conducted at four EoE referral centers (Pisa, Padova, Humanitas Research Hospital, Milano Policlinico San Donato). We enrolled consecutive patients undergoing esophagogastroduodenoscopy (EGD) for suspected or known EoE who had performed blood counts within one month before EGD. Histological remission and non-EoE-related dysphagia (NED) were defined according to current guidelines on EoE. Endoscopic characteristics were classified according to the EoE reference score (EREFS). Demographic, clinical and full blood count data were collected. After the EGD, all patients completed the Dysphagia Symptom Questionnaire over 14 days (DSQ). Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. ROC curve analysis was used to assess the diagnostic accuracy. Spearman’s test was used for correlations. Significance threshold was p<0.05.

Results

We included 210 consecutive patients. Of these, 123 had EoE (58.5% active; 41.5% in histological remission) while 87 had non-EoE dysphagia (NED). Characteristics in Table 1. Absolute eosinophil count (AEC) of active EoE was significantly higher than NED (335 vs 90/mm3; p<0.001), and so was eosinophil percentage (4.6% vs 1.1%; p<0.001), and median lymphocyte percentage (30 vs 27%; p<0.001). ROC curve analysis showed that a cut-off of 155 eosinophils/mm3 had an AUC of 0.85, with 71% specificity and 87% sensitivity for the identification of EoE among patients with dysphagia (Figure 1a). Other ROC analyses on the diagnosis of EoE reported in Table 2. With regards to disease monitoring, only eosinophil counts differed significantly between EoE and NED. Median AEC of active EoE was higher than EoE in remission (335 vs 200/mm3; p<0.01), and so was eosinophil percentage (4.6 vs 1.4%; p<0.001) (Table 3). Based on ROC analysis, a cut-off of 325 eosinophils/mm3 had and AUC of 0.70 for the identification of histological remission in EoE, with a specificity of 52.7%% and sensitivity of 82.3% (Figure 1b) (Table 3). There was modest positive correlation between AEC and the EREFS with Spearman’s Rho of 0.4 (p<0.0001), but there was no correlation between AEC and DSQ scores (Rho= -0.01; p=0.9).

Conclusion

Our results show that the AEC in peripheral blood has good accuracy for the diagnosis of EoE in patients with dysphagia and moderate accuracy for monitoring histological disease activity. In addition, AEC was modestly correlated with endoscopic disease activity (EREFS score) but not with symptoms.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established interventional treatment for complications of portal hypertension. Post-TIPS transient or persistent acute bilirubin elevation (ABE) is common, possibly due to impairment of portal perfusion. The outcomes of patients with ABE is not clear.

Aims & Methods

This study investigates the incidence, clinical outcomes, and prognostic factors associated with ABE in cirrhotic patients undergoing TIPS. Between January 2009 and November 2022, 1,287 patients (882 men, 405 women; mean age, 52 years) were included in this retrospective analysis. ABE was defined as a total serum bilirubin level exceeding 85.5 μmol/L (5 mg/dL) within one week after TIPS. Statistical analyses included the Kaplan-Meier method, log-rank test, multivariate Cox regression, and stepwise regression.

Results

Post-TIPS ABE occurred in 67 patients (5.2%). Patients with ABE had significantly higher baseline Child-Pugh scores (8.39 ± 1.62 vs. 7.41 ± 1.54, P < 0.001) and MELD scores (13.98 ± 4.13 vs. 10.72 ± 2.99, P < 0.001). Refractory ascites as the TIPS indication was more frequent in the ABE group (17.91% vs. 7.21%, P = 0.001). ABE was associated with a significantly higher incidence of hepatic encephalopathy (HE): 62.7% vs. 38.3% at 1 year and 80.6% vs. 62.8% at 5 years (P = 0.042). During follow-up, 441 patients died, with causes including liver failure (n = 129), gastrointestinal bleeding (n = 100), sepsis (n = 16), multi-organ dysfunction (MOD) (n = 41), hepatocellular carcinoma (HCC) (n = 43), and other or unknown causes (n = 112). Survival rates were significantly lower in the ABE group: 1-year (52.2% vs. 85.2%), 3-year (34.3% vs. 68.3%), and 5-year (25.4% vs. 46.6%) (P < 0.001). Multivariate analysis identified ABE (hazard ratio [HR]: 2.09; 95% confidence interval [CI]: 1.41–3.10; P < 0.001), age (HR: 1.05; 95% CI: 1.04–1.06; P < 0.001), albumin level (HR: 0.95; 95% CI: 0.94–0.97; P < 0.001), pre-TIPS grade 4 HE (HR: 1.93; 95% CI: 1.19–3.14; P = 0.008), presence of HCC (HR: 1.81; 95% CI: 1.24–2.65; P = 0.002), baseline MELD score (HR: 1.09; 95% CI: 1.04–1.14; P < 0.001), and change in MELD score (HR: 1.08; 95% CI: 1.06–1.11; P < 0.001) as independent predictors of post-TIPS mortality.

Conclusion

AEB is not rare in cirrhotic patients undergoing TIPS and is associated with an increased risk of HE and mortality. Risk factors for post-TIPS mortality include AB, older age, higher and fluctuating MELD scores, concurrent HCC, severe pre-TIPS HE, and lower albumin levels. Early identification, close monitoring, and prompt management of complications are essential to improving clinical outcomes and reducing the risk of liver failure after TIPS.

Clinical Case Summary

Introduction: Rituximab, a monoclonal anti-CD20 antibody, is widely used for treating hematologic malignancies and autoimmune disorders due to its B-cell depleting action. While gastrointestinal side effects like diarrhea are seen in up to 15% of patients, these are typically mild and self-limiting. Severe colitis is a rare but increasingly recognized complication.
Case Description: A 76-year-old diabetic male with a history of ACS (post-PTCA in 2021) presented with 2 months history of generalized abdominal pain, watery diarrhea (6–7 episodes/day), and weight loss. He had a history of follicular lymphoma diagnosed 4 years prior, treated with 6 cycles of CHOP-R followed by rituximab maintenance (375 mg/m² every 3 months). Symptoms began after the 6th maintenance dose.Physical exam revealed mild pallor;abdomen was soft, nontender. Labs showed normocytic anemia and mild neutrophilic leukocytosis. Stool tests were negative for common pathogens, including C. difficile. The patient was planned for a Colonoscopy, which revealed ulcers over the ileocecal valve and rectal erosions. Biopsies showed mixed inflammatory infiltrates, cryptitis, crypt abscesses, and crypt rupture, consistent with severe active ileocolitis. AFB culture and GeneXpert were negative for tuberculosis.The patient was started on oral mesalamine (500 mg TID) along with Rifaximin(400mg) BD for 2 weeks, showing marked clinical improvement.
Discussion: Rituximab-induced colitis is rare and poorly understood. It may result from disruption of mucosal immunoregulation due to B-cell depletion, leading to T-cell-mediated inflammation. Histology may resemble patterns seen in GVHD or autoimmune enteropathy. Most cases resolve with supportive care and discontinuation of the drug; however, some, like this case, may require treatment in the form of 5ASA, or steroids.There is no previous data on the use of rifaximin in such cases. Differentiating drug-induced IBD from primary IBD remains a diagnostic challenge.

References

There is limited evidence in the literature establishing a definitive association between rituximab therapy and the onset of colitis. However, emerging hypotheses suggest that rituximab-induced depletion of peripheral CD19+ B cells and colonic CD20+ lymphoid aggregates may disrupt mucosal immune homeostasis, thereby contributing to structural alterations in the intestinal architecture and promoting inflammation.
The role of the gut microbiota in the pathogenesis and persistence of mucosal inflammation in inflammatory bowel disease (IBD) provides a rationale for the therapeutic use of antibiotics in selected cases. While systemic antibiotics such as ciprofloxacin and metronidazole have demonstrated clinical efficacy in IBD management, their utility may be limited in drug-induced colitis due to the potential for systemic adverse effects.
In contrast, rifaximin, a non-systemic, presents a favorable safety profile and has shown promise as a therapeutic option in both idiopathic and drug-induced enterocolitis. Its targeted antimicrobial activity within the gastrointestinal tract, combined with minimal systemic exposure, renders it an attractive alternative. However, further prospective, randomized studies are warranted to substantiate its efficacy and long-term safety in this context.