BACKGROUND AND AIMS: There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. METHODS: We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis. RESULTS: We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications. CONCLUSIONS: Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.

• Keywords
• Antibodies, Biological therapy, Crohn’s disease, IBD, Monoclonal, Tumor Necrosis Factor-alpha, Ulcerative colitis,
• MeSH
• Crohn Disease * chemically induced   drug therapy   MeSH
• Adult MeSH
• Gastrointestinal Agents adverse effects   MeSH
• Antibodies, Monoclonal, Humanized MeSH
• Inflammatory Bowel Diseases * chemically induced   drug therapy   MeSH
• Infliximab adverse effects   MeSH
• Humans MeSH
• Colitis, Ulcerative * chemically induced   drug therapy   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Gastrointestinal Agents MeSH
• Antibodies, Monoclonal, Humanized MeSH
• Infliximab MeSH
• vedolizumab MeSH Browser

BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.

• Keywords
• Biobetter, Bioinnovative, Inflammatory bowel disease, Subcutaneous infliximab, Tumour necrosis factor-α inhibitors, Vedolizumab,
• MeSH
• Crohn Disease * drug therapy   MeSH
• Adult MeSH
• Gastrointestinal Agents * therapeutic use   adverse effects   administration & dosage   MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   adverse effects   administration & dosage   MeSH
• Remission Induction MeSH
• Induction Chemotherapy methods   MeSH
• Infliximab * therapeutic use   administration & dosage   adverse effects   MeSH
• Injections, Subcutaneous MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Colitis, Ulcerative * drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Gastrointestinal Agents * MeSH
• Antibodies, Monoclonal, Humanized * MeSH
• Infliximab * MeSH
• vedolizumab MeSH Browser

BACKGROUND: Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations. METHODS: A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients. SubsequentIy, α4β7 occupancy on peripheral blood [PB] and intestinal lamina propria [LP] tissues was investigated on various cellular subsets in patients undergoing lower endoscopy on infusion day. Cellular localisation of vedolizumab-bound α4β7 and effects on M1 and M2 macrophages were also explored. RESULTS: A total of 161 inflammatory bowel disease [IBD] patients were included. Among 129/161 patients intensified during maintenance [Week 14 onward], pre-intensification trough levels were comparable or higher among those subsequently attaining post-optimisation clinical, biomarker, and endoscopic remission, compared with non-remitting patients [p = 0.09, 0.25, 0.04, respectively]. Similar results were demonstrated for those dose-optimised during induction [Week 6, n = 32]. In the immune sub-study [n = 43], free α4β7 receptors at trough were similarly low among patients with/without mucosal healing, on PB T cells [p = 0.15], LP T cells [p = 0.88], and on PB eosinophils [p = 0.08]. Integrin receptors on M1 and M2 macrophages were also saturated by low levels of vedolizumab and anti-inflammatory cytokine secretion was not increased. Co-localisation and dissociation experiments demonstrated membranal α4β7 receptors of two origins: non-internalised and newly generated α4β7, but re-binding was still complete at very low concentrations. CONCLUSIONS: These results do not support pharmacokinetics as the mechanism responsible for loss of response to vedolizumab, nor do they support a need for higher drug concentration to enhance vedolizumab's immune effects. Higher pre-escalation levels may indicate less clearance [less severe disease] and higher likelihood of subsequent re-gained response, regardless of therapy escalation.

• Keywords
• IBD, Vedolizumab, clinical outcome, immunology, pharmacokinetics,
• MeSH
• Biomarkers analysis   MeSH
• C-Reactive Protein analysis   MeSH
• Adult MeSH
• Endoscopy, Gastrointestinal MeSH
• Gastrointestinal Agents administration & dosage   MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   MeSH
• Inflammatory Bowel Diseases drug therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Macrophages drug effects   MeSH
• Cell Adhesion Molecules analysis   MeSH
• Mucoproteins analysis   MeSH
• Serum Albumin analysis   MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Names of Substances
• Biomarkers MeSH
• C-Reactive Protein MeSH
• Gastrointestinal Agents MeSH
• Antibodies, Monoclonal, Humanized MeSH
• MADCAM1 protein, human MeSH Browser
• Cell Adhesion Molecules MeSH
• Mucoproteins MeSH
• Serum Albumin MeSH
• vedolizumab MeSH Browser

BACKGROUND & AIMS: Tofacitinib and upadacitinib are Janus kinase (JAK) inhibitors that are increasingly used for the treatment of acute severe ulcerative colitis (ASUC). However, comparative analyses of safety and effectiveness have not been performed for their use in this setting. METHODS: This multicenter, retrospective study enrolled hospitalized adult patients treated with tofacitinib or upadacitinib for ASUC between January 2019 and June 2024. The main outcomes were clinical response, clinical remission, and colectomy-free survival. Propensity-adjusted analyses using inverse probability treatment weighting, and double robust estimations were used to control for confounding factors. RESULTS: In total, 111 patients (60 tofacitinib, 51 upadacitinib) were enrolled across 23 international centers. JAK inhibitors were used to induce response in 86 patients (77%) and used to maintain response after adequate intravenous steroid response in 25 (23%). The median follow up was 31 weeks (interquartile range, 13-64 weeks). Between days 3 and 7 after treatment initiation, upadacitinib was associated with greater response rates (84% vs 54%; P = .02), but response/remission was comparable at day 98 (45%/36% vs 55%/48%) and day 182 (29/29% vs 39/34%). Sub-analyses for JAK inhibitor use as salvage therapy (tofacitinib [n = 35] vs upadacitinib [n = 31]) showed similar effectiveness outcomes across both groups. The probabilities of colectomy-free survival at days 98 and 182 for tofacitinib and upadacitinib were 79% and 75% and 80% and 78%, respectively, with no significant differences in the comparison of survival curves (P = .99). Treatment failure rates (where JAK inhibitors were used to maintain remission) were similar at days 98 and 182. The frequency of adverse events was comparable. CONCLUSION: Tofacitinib and upadacitinib appear to have similar effectiveness and safety profiles when used for the treatment of ASUC.

• Keywords
• Acute Severe Ulcerative Colitis, Colectomy, Effectiveness, Janus Kinase Inhibitors, Tofacitinib, Ulcerative Colitis, Upadacitinib,
• Publication type
• Journal Article MeSH

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.

• Keywords
• Anti-TNF Cessation, Crohn’s Disease, Prediction,
• MeSH
• Adalimumab therapeutic use   MeSH
• Crohn Disease * drug therapy   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Infliximab therapeutic use   MeSH
• Tumor Necrosis Factor Inhibitors * therapeutic use   MeSH
• Humans MeSH
• Necrosis MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Adalimumab MeSH
• Immunosuppressive Agents MeSH
• Infliximab MeSH
• Tumor Necrosis Factor Inhibitors * MeSH

BACKGROUND AND AIMS: Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on second- and third-line biologics are limited. We present the first direct comparison of second- and third-line biologics in pCD patients with active perianal disease previously treated with first-line anti-TNFs. METHODS: A multicenter retrospective cohort study included adult patients with pCD who failed first-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging or transrectal ultrasound) and healing, and clinical remission. Propensity score matching (PSM) was used to adjust for baseline differences. RESULTS: A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the second and third-line treatment groups, respectively. In the second-line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI, 1.94-10.28, P < .001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI, 2.39-11.71, P < .001). In the third-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI, 2.6-38.4, P < .001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI, 2.99-48.47, P < .001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI, 1.07-10.07, P = .038). CONCLUSION: In pCD patients failing anti-TNFs as first-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNF as second or third-line therapy.

• Keywords
• Crohn’s, biologics, fistulas, perianal, second line, third line,
• MeSH
• Biological Products * therapeutic use   MeSH
• Crohn Disease * drug therapy   diagnostic imaging   MeSH
• Adult MeSH
• Gastrointestinal Agents * therapeutic use   MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Remission Induction MeSH
• Tumor Necrosis Factor Inhibitors therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Anus Diseases * drug therapy   MeSH
• Retrospective Studies MeSH
• Propensity Score MeSH
• Ustekinumab * therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Names of Substances
• Biological Products * MeSH
• Gastrointestinal Agents * MeSH
• Antibodies, Monoclonal, Humanized MeSH
• Tumor Necrosis Factor Inhibitors MeSH
• Ustekinumab * MeSH
• vedolizumab MeSH Browser