Rates of Postoperative Recurrence of Crohn's Disease and Effects of Immunosuppressive and Biologic Therapies.

Background & Aims: The Rutgeerts' scoring system is used to evaluate patients with Crohn's disease (CD) following ileocolic resection, based on endoscopic findings at the anastomosis and in the neoterminal ileum. We investigated rates of clinical and surgical recurrence of CD after surgery and effect of therapy modification based on post-operative endoscopic findings.

Methods: We collected data from 365 adults with CD (20% with Rutgeerts' score i0, 10% with score i1, 49% with score i2, 12% with score i3, 9% with score i4) who underwent ileocolonoscopy within 12 months of ileocolic resection with anastomosis from 2000 through 2013 at 2 centers in Belgium and France.

Correlation of Stool Frequency and Abdominal Pain Measures With Simple Endoscopic Score for Crohn's Disease.

Background: The Crohn's Disease Activity Index (CDAI) has been criticized for being weakly correlated with bowel inflammation. We assessed correlation between Simple Endoscopic Score for Crohn's Disease (SES-CD) and individual CDAI items stratified by disease location to better understand this relationship.

Methods: We pooled patient-level data from 3 placebo-controlled Crohn's disease (CD) trials that tested adalimumab, upadacitinib, and risankizumab.

Reliability of Endoscopic Evaluation of Postoperative Recurrent Crohn's Disease.

Endoscopic evaluation for postoperative recurrence of Crohn's disease (CD) is routinely integrated into clinical practice. The Rutgeerts score (RS) was developed to grade the severity of endoscopic postoperative CD recurrence and has been integrated into clinical practice guidelines and utilized as an endpoint in interventional trials. However, the operating properties of the RS have not been fully assessed.

Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn's Disease.

Background & Aims: Although ustekinumab is an effective therapy for moderate to severe Crohn's disease (CD), its effects on the microscopic manifestations of CD are unknown.

Methods: We evaluated the effects of ustekinumab on histologic CD activity in an analysis of data from 251 participants in phase 3 induction and maintenance studies. Two endoscopic biopsy samples were collected at weeks 0, 8, and 44 from the ileum, splenic flexure, and rectum (18 biopsy samples from each patient).

IM-UNITI: Three-year Efficacy, Safety, and Immunogenicity of Ustekinumab Treatment of Crohn's Disease.

Background And Aims: Following induction/maintenance treatment in the UNITI/IM-UNITI studies of ustekinumab for Crohn's disease, patients entered a long-term extension for up to 5 years from induction. Efficacy through 152 and safety through 156 weeks are reported.

Methods: At IM-UNITI Week 44, 567 ustekinumab-treated patients entered the long-term extension and continued to receive blinded subcutaneous ustekinumab on their assigned dose interval, without any subsequent dose adjustment.

Early Dose Optimisation of Golimumab in Nonresponders to Induction Treatment for Ulcerative Colitis Is Effective and Supported by Pharmacokinetic Data.

Background And Aims: In nonresponders to golimumab induction for ulcerative colitis, we assessed clinical response rates and golimumab serum concentrations when the 100-mg dose was used early in the course of maintenance.

Methods: This post-hoc analysis of golimumab maintenance dosing [in the PURSUIT-M study] examined clinical outcomes and golimumab concentrations in early [Week 6] responders and nonresponders to induction, including subgroups based on body weight.

Results: In nonresponders to golimumab induction [assessed at Week 6], the 100-mg maintenance dose [starting at Week 6] resulted in a meaningful proportion [28.

Immunogenicity of Golimumab and its Clinical Relevance in Patients With Ulcerative Colitis.

Background: Antidrug antibody (ADA) detection with standard bridging enzyme immunoassays (EIA) can yield false-negative results or underestimate titers through drug interference. A more sensitive assay was needed to determine clinical impact of antigolimumab antibodies.

Methods: A high-sensitivity, drug-tolerant EIA (DT-EIA) was developed and cross-validated against the original EIA, and samples from induction/maintenance studies in golimumab-treated patients with ulcerative colitis were analyzed for ADAs using both methods.

Efficacy and Safety of Adalimumab by Disease Duration: Analysis of Pooled Data From Crohn's Disease Studies.

Background And Aims: Analyses of Crohn's Disease [CD] studies of anti-TNF agents, including adalimumab, have reported higher remission rates among patients with shorter disease duration. To further explore the relationship between disease duration and clinical efficacy, we analysed a larger patient cohort.

Methods: Data were pooled from 10 clinical trials in patients with moderately to severely active CD who received treatment with either adalimumab or placebo.

Gene and Mirna Regulatory Networks During Different Stages of Crohn's Disease.

Background And Aims: Early treatment of Crohn's disease [CD] is required in order to optimize patient outcomes. To this end, we need to gain a better understanding of the molecular changes at the onset of CD.

Methods: As a model for the earliest mucosal CD lesions, we study post-operative recurrent CD [Rutgeerts score ≥ i2b].

Difference in Pathomechanism Between Crohn's Disease and Ulcerative Colitis Revealed by Colon Transcriptome.

Background: We aim to identify the differences in colonic mucosal transcriptome between Crohn's disease (CD) and ulcerative colitis (UC) for a better understanding of the molecular pathology.

Methods: Differentially expressed genes (DEG) in the colonic mucosa of CD and UC were identified with a global gene expression microarray dataset generated from the colon biopsies of CD and UC patients and normal controls. The DEGs were then processed to identify altered pathways and modularized DEGs and pathways.

No Change in Determining Crohn's Disease Recurrence or Need for Endoscopic or Surgical Intervention With Modification of the Rutgeerts' Scoring System.

The postoperative endoscopic recurrence score, commonly referred to as the Rutgeerts score, was designed to predict clinical recurrence risk in Crohn's disease (CD) patients undergoing ileocolonic resection based on early endoscopic findings at the anastomosis and in the neoterminal ileum. In the pivotal publication, the i2 category, including aphthous lesions in the terminal ileum as well as ileocolonic anastomosis lesions, had a heterogeneous recurrence risk. Because anastomotic ulcers were suspected to be postsurgical ischemic lesions and less predictive of progressive disease, a modified Rutgeerts score (mRS) was proposed: i2a, lesions confined to the anastomosis ±<5 isolated aphthous ulcers in the ileum; i2b, more than 5 aphthous ulcers in the ileum with normal mucosa in between, ± anastomotic lesions.

Combination Therapy With Infliximab and Azathioprine Improves Infliximab Pharmacokinetic Features and Efficacy: A Post Hoc Analysis.

Background & Aims: Among immunosuppressive- and biologic-naïve patients with moderately-to-severely active Crohn's disease (CD), a higher proportion of those treated with the combination of infliximab and azathioprine achieved corticosteroid-free remission at week 26 (CSFR26) than those given infliximab monotherapy; patients given the combination therapy also had higher serum concentrations of infliximab. Enhanced benefit of combination therapy may occur through synergistic modes of action or the influence of azathioprine on infliximab pharmacokinetics.

Methods: We analyzed data from 206 patients from whom week 30 serum samples were available: 97 received infliximab monotherapy (5 mg/kg, n = 97) and 109 received combination therapy (2.

Continuous Clinical Response Is Associated With a Change of Disease Course in Patients With Moderate to Severe Ulcerative Colitis Treated With Golimumab.

Background: Responders to induction treatment sustain continuous clinical response (CCR) through 1 year in about 50% of patients in PURSUIT-M trial with golimumab maintenance in ulcerative colitis (UC). This post hoc analysis of PURSUIT-M describes the 1-year clinical, endoscopic, quality of life (QoL), and biomarker and 4-year clinical outcome in patients with sustained response to golimumab therapy for UC.

Methods: We compared clinical, endoscopic, QoL, and calprotectin outcomes in CCR and non-CCR patients through 54 weeks in PURSUIT-M.

Gene Expression Signature for Prediction of Golimumab Response in a Phase 2a Open-Label Trial of Patients With Ulcerative Colitis.

Golimumab, a tumor necrosis factor antagonist, is an effective treatment for patients with moderate-to-severe ulcerative colitis (UC); however, more than 50% of initial responders lose their response to the drug within the first year of therapy. A gene expression signature identified in colon biopsies collected before treatment was associated with response to infliximab, and was subsequently refined to associate with mucosal healing in response to golimumab. We performed a phase 2a open-label study of 103 golimumab-treated patients with moderate-to-severe UC to test whether the baseline gene expression signature could be used to predict which patients would achieve mucosal healing, clinical response, and clinical remission at weeks 6 and 30 of treatment.

Long-Term Benefit of Golimumab for Patients with Moderately to Severely Active Ulcerative Colitis: Results from the PURSUIT-Maintenance Extension.

Background And Aims: To evaluate the safety and efficacy of 3 additional years of subcutaneous golimumab maintenance in patients with moderately to severely active ulcerative colitis.

Methods: The PURSUIT-maintenance long-term extension enrolled patients who had completed placebo or golimumab 50 mg or 100 mg treatment every 4 weeks [q4w] through Week 52 and evaluations at Week 54 [n = 666]; treatment continued through Week 212. Patients receiving placebo were discontinued after study unblinding.

Efficacy of Ustekinumab for Inducing Endoscopic Healing in Patients With Crohn's Disease.

Background & Aims: We evaluated the ability of ustekinumab, a monoclonal antibody against the p40 subunit of interleukins 12 and 23, to induce endoscopic healing in patients with moderate to severe Crohn's disease (CD).

Methods: We performed an endoscopy substudy of 334 patients with moderate to severe CD participating in 3 randomized controlled phase 3 studies to determine the safety and efficacy of ustekinumab induction and maintenance therapy. All patients underwent colonoscopy at baseline and week 8 of the induction studies and at week 44 of the maintenance study; all colonoscopies were assessed by a blinded central reader.

Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

Background: In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported.

Methods: UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients.

Performance of Crohn's disease Clinical Trial Endpoints based upon Different Cutoffs for Patient Reported Outcomes or Endoscopic Activity: Analysis of EXTEND Data.

Background: Clinical trial endpoints for Crohn's disease (CD) activity correlate poorly with mucosal inflammation; to assess treatment efficacy, patient-reported outcomes and endoscopic assessments are preferred. This study assessed the impact on treatment efficacy estimations of using different definitions of clinical and endoscopic remission and endoscopic response, and of using site- or central-based endoscopy evaluation.

Methods: This post hoc analysis of data fromEXTEND (extend the safety and efficacy of adalimumab through endoscopic healing), a placebo (PBO)-controlled, randomized trial of adalimumab (ADA) for mucosal healing, included adults with moderate-to-severe CD.

Mucosal Healing and Long-term Outcomes of Patients With Inflammatory Bowel Diseases Receiving Clinic-Based vs Trough Concentration-Based Dosing of Infliximab.

Background & Aims: The Trough Concentration Adapted Infliximab Treatment (TAXIT) trial demonstrated that maintaining infliximab trough concentrations at 3 to 7 μg/mL is most effective at inducing remission in patients with inflammatory bowel diseases (IBDs), with fewer flares than clinic-based dosing. We performed a follow-up analysis of study participants to explore the correlation between trough dosing strategy and mucosal healing, continued infliximab use, and rates of hospitalization, surgery, and steroid use.

Methods: This was a retrospective single-center study of 226 patients with IBD who completed the maintenance phase of TAXIT, performed at the University Hospitals of Leuven in Belgium.

Long-term safety of adalimumab in clinical trials in adult patients with Crohn's disease or ulcerative colitis.

Background: Adalimumab is used to treat moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) when conventional therapies fail.

Aim: To update long-term adalimumab safety from CD and UC trials; the previous report was CD only, 3160 patients/3402 patient-years (PYs).

Methods: Treatment-emergent adverse events (AEs; first dose to 70 days after last dose/December 31, 2015) in adults in phase 2/3 and 3/3b trials and open-label extensions were coded using Medical Dictionary for Regulatory Activities (MedDRA-v18.

Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

Background: Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm.

Methods: CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics.

Genetic and Transcriptomic Bases of Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease.

Background: Intestinal barrier defects are common in patients with inflammatory bowel disease (IBD). To identify which components could underlie these changes, we performed an in-depth analysis of epithelial barrier genes in IBD.

Methods: A set of 128 intestinal barrier genes was selected.

Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial.

Background: Patients with long-standing UC have an increased risk for the development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is still to be defined.

Objective: To compare the performance of CE to VC for the detection of neoplastic lesions in patients with long-standing UC.

Randomised non-inferiority trial: 1600 mg versus 400 mg tablets of mesalazine for the treatment of mild-to-moderate ulcerative colitis.

Background: High concentration mesalazine formulations are more convenient than conventional low concentration formulations for the treatment of ulcerative colitis (UC).

Aim: To compare the efficacy and safety of 1600 mg and 400 mg tablet mesalazine formulations.

Methods: Patients with mild-to-moderate active UC (Mayo Clinic Score >5; N=817) were randomised to 3.