Impact of Prior Biologic Exposure on Ozanimod Efficacy and Safety in the Phase 3 True North Clinical Trial.

Introduction: Patients with ulcerative colitis (UC) and prior biologic failure may have reduced or delayed efficacy with subsequent advanced therapies. This analysis evaluated the efficacy and safety of ozanimod during the True North (TN) study and its open-label extension (OLE) in biologic-exposed patients with UC.

Methods: TN was a randomized, placebo-controlled 52-week trial (10-week induction, 42-week maintenance period).

Anti-TNF Non-Response in Ulcerative Colitis: Correcting for Mucosal Drug Exposure Reveals Distinct Cytokine Profiles.

Introduction: It remains unclear why up to 30% of ulcerative colitis patients (UC) do not respond to tumor necrosis factor inhibitors (TNFi). Validated biomarkers for (non-)response ((N)R) are lacking. Most studies investigating underlying mechanisms do not differentiate between pharmacokinetic and inflammatory mechanisms.

Hypercoagulation after Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study.

Background & Aims: Venous thromboembolism is a serious complication during and following hospitalization with acute severe ulcerative colitis (ASUC). We evaluated serial thrombotic profiles of patients with ASUC from the point of hospitalization up to 12 weeks post-discharge and compared these with control patients with quiescent UC.

Methods: Twenty-seven patients with ASUC and 25 control patients with quiescent ulcerative colitis (UC) were recruited.

Clinical relevance of calprotectin in patients with perianal fistulas in Crohn's disease and cryptoglandular fistulas.

Background And Aims: Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics.

Methods: In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included.

Efficacy and safety of filgotinib as induction and maintenance therapy for Crohn's disease (DIVERSITY): a phase 3, double-blind, randomised, placebo-controlled trial.

Background: There is a need for efficacious therapies for patients with Crohn's disease that are better tolerated and more durable than available treatments. We aimed to evaluate the efficacy and safety of filgotinib, an oral Janus kinase 1 preferential inhibitor, for treating Crohn's disease.

Methods: This phase 3, double-blind, randomised, placebo-controlled trial was conducted in 371 centres in 39 countries.

Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study.

Background: Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.

Methods: VIVID-1 was a global phase 3, randomised, double-blind, double-dummy, placebo-controlled and active-controlled, treat-through study.

Vedolizumab to prevent postoperative recurrence of Crohn's disease (REPREVIO): a multicentre, double-blind, randomised, placebo-controlled trial.

Background: Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease.

Immunogenicity of Therapeutic Antibodies Used for Inflammatory Bowel Disease: Treatment and Clinical Considerations.

The introduction of tumor necrosis factor inhibitors has led to a paradigm shift in the management of inflammatory bowel disease (IBD). The subsequent introduction of both anti-integrins and cytokine blockers has since expanded the biologic armamentarium. However, immunogenicity, defined as the production of anti-drug antibodies (ADAs) to the prescribed biopharmaceutical, means a significant fraction of patients exposed to biologic agents will experience a secondary loss of response to one or more of the drugs.

Risankizumab Is Associated With Normalization of Biomarkers in Patients With Crohn's Disease: Results From the Phase 3 ADVANCE, MOTIVATE, and FORTIFY Studies.

Background And Aims: Normalization of high-sensitivity C-reactive protein [hs-CRP] and fecal calprotectin [FCP] are suggested Crohn's disease [CD] intermediate treatment targets. This analysis evaluates achievement of biomarker normalization and the relationship between improvements in biomarker concentrations and clinical and endoscopic outcomes among patients treated with risankizumab.

Methods: This post hoc analysis included patients with moderately to severely active CD and elevated baseline hs-CRP [> 5 mg/L] or FCP [> 250 µg/g] concentrations from the 12-week ADVANCE and MOTIVATE induction studies, and the 52-week FORTIFY maintenance study.

Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

Background: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.

Methods: Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance.

Gut Microbiota Features in Relation to Fecal Microbiota Transplantation Outcome in Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Background & Aims: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition.

Methods: MEDLINE, Embase, and Cochrane were systematically searched through August 2024 for relevant studies.

Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4 T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease.

Background & Aims: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response.

Methods: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell B and T cell receptor sequencing (BCR/TCR-seq); serum proteomics; and multiparametric flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response.

Fistulizing Perianal Disease as a First Manifestation of Crohn's Disease: A Systematic Review and Meta-Analysis.

: Incidences of perianal fistulas (PAFs) as a first manifestation of Crohn's disease (CD) vary widely in the literature. Aim: To analyse the percentage of patients with a PAF preceding CD diagnosis and assess the time to diagnosis. : A systematic literature search was conducted.

Shorter Crohn's Disease Duration Is Associated With Better Clinical and Endoscopic Outcomes With Risankizumab in Phase 3 Studies.

Background And Aims: Early biologic therapy treatment has demonstrated better outcomes in Crohn's disease (CD). We evaluated the impact of CD duration in patients with moderately to severely active CD treated with risankizumab therapy.

Methods: This post hoc analysis evaluated clinical, endoscopic, and safety outcomes by baseline CD duration (<2, 2-5, >5-10, and >10 years) in patients from ADVANCE, MOTIVATE, and FORTIFY.

Efficacy and safety of risankizumab by baseline corticosteroid use and achievement of corticosteroid-free clinical and endoscopic outcomes in patients with moderately to severely active Crohn's disease.

Background: Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD).

Aim: To evaluate the corticosteroid-sparing effect of risankizumab in CD.

Methods: During the 12-week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent.

Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials.

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown.

Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis.

Design, Setting, And Participants: Two phase 3 randomized clinical trials were conducted.

Re-evaluating Methods for Assessing Differences in Response in Ileal vs. Colonic Crohn's Disease: A Post-hoc Analysis of the FITZROY Trial.

Background And Aims: The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease (CD). We aimed to determine whether disease location affects response to filgotinib, a Janus kinase (JAK) inhibitor, in patients with moderate-to-severely active Crohn's disease (CD) and applying appropriate methods to account for differences in measuring disease activity in the ileum compared to the colon.

Methods: This post-hoc analysis of data from the FITZROY phase 2 trial (NCT02048618) compared changes in the Crohn's Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn's Disease (SES-CD) amongst patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200 mg daily or placebo.

Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn's disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial.

Background: Retrospective research suggests that excision of the affected mesentery can improve outcomes after an ileocoecal resection in Crohn's disease. However, prospective data from randomised controlled trials are scarce. We aimed to compare rates of postoperative recurrence in patients with Crohn's disease who underwent extended mesenteric resection.