Magro, F

Abstract Background The expanding use of biologic and small-molecule therapies for ulcerative colitis (UC) has raised concerns regarding perioperative safety. We conducted a network meta-analysis to compare short-term postoperative complications associated with preoperative exposure to these agents in patients undergoing colorectal surgery. Methods We systematically searched PubMed, Web of Science, and the Cochrane Library through September 15, 2025, for cohort studies of adults with UC who were exposed to biologic or small-molecule therapy within 12 weeks prior to surgery. Interventions included biologic therapy, small-molecule therapy, and no biologic or small-molecule therapy (control). The primary outcome was overall postoperative complications at 30 and 90 days. Venous thromboembolism (VTE) was assessed as a key secondary outcome. Random-effects network meta-analysis was performed using risk ratios (RRs) with 95% confidence intervals (CIs). Results Sixteen retrospective cohort studies involving 3235 patients were included. At 30 days, ustekinumab and tofacitinib were associated with lower overall postoperative complication rates than control (RR: 0.29; 95% CI: 0.09-0.96; and RR: 0.66; 95% CI: 0.46-0.96, respectively). Anti-tumor necrosis factor (TNF) therapy was associated with higher complication rates compared with vedolizumab, ustekinumab, and tofacitinib at 30 days (RR: 1.27; 95% CI: 1.00-1.63; RR: 3.67; 95% CI: 1.12-12.03; and RR: 1.61; 95% CI: 1.14-2.27, respectively). At 90 days, anti-TNF therapy was associated with higher complication rates than control (RR 1.20, 95% CI 1.03-1.40), although the 90-day analysis was based on limited data. VTE rates were similar across treatments at both time points. Conclusion Preoperative ustekinumab and tofacitinib were associated with fewer 30-day postoperative complications than control or anti-TNF therapy, while vedolizumab was associated with fewer complications than anti-TNF therapy. At 90 days, anti-TNF therapy was associated with higher complication rates compared with control. These findings, particularly at 90 days based on limited data, should be interpreted with caution and require confirmation in well-designed prospective studies with rigorous adjustment for confounding factors.

Abstract Background and Aims The long-term efficacy and safety of upadacitinib in patients with moderate to severe Crohn’s disease (CD) were evaluated in the U-ENDURE Long-Term Extension (LTE) study. Here we report the results after 2 years of total maintenance treatment. Methods U-ENDURE is an ongoing 240-week LTE study conducted at 243 sites across 43 countries (first patient enrolled in LTE 21 March 2019). Patients who completed the 52-week maintenance study continued their previously assigned treatment, once-daily upadacitinib 15 mg or upadacitinib 30 mg. Efficacy was analyzed at week 48 of the LTE; safety was analyzed in the cumulative study population (combined 52 week maintenance and 48 week LTE) and the LTE study population only (cutoff date: 19 December 2023). Results From LTE week 0 to week 48, as-observed efficacy rates for clinical remission (per stool frequency/abdominal pain score, upadacitinib 15 mg: 78.3% to 82.9%; upadacitinib 30 mg: 84.7% to 76.6%; per CD Activity Index, upadacitinib 15 mg: 81.3% to 83.1%; upadacitinib 30 mg: 86.1% to 86.8%), endoscopic response (upadacitinib 15 mg: 59.6% to 67.1%; upadacitinib 30 mg: 71.2% to 69.6%), inflammatory biomarkers, and quality-of-life outcomes remained stable. The safety profile of the cumulative maintenance population observed through LTE week 48 was consistent with previous trials in the upadacitinib CD program. Treatment-emergent adverse event rates for the cumulative maintenance population were 283.1 and 273.4 events/100 patient-years for upadacitinib 15 mg and upadacitinib 30 mg, respectively. Event rates of serious treatment-­emergent adverse events were 16.0 events/100 patient-years for upadacitinib 15 mg and 14.6 events/100 patient-years for upadacitinib 30 mg. The most common adverse events of special interest (≥ 5.0 events/100 patient-years) were hepatic disorder, lymphopenia, creatine phosphokinase elevation, herpes zoster, and anemia. There was 1 treatment-emergent adverse event of suicide leading to death. Conclusion Sustained clinical, endoscopic, quality-of-life, and biomarker outcomes were observed in patients who were initial responders to upadacitinib and completed 2 years of maintenance therapy, with no new safety signals identified. Clinical trial identifier U-ENDURE; ClinicalTrials.gov number, NCT03345823.

Abstract Background and Aims Over 10% of patients with Crohn’s disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn’s disease patients with permanent ileostomy. Methods MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn’s disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence. Results Thirty cohort studies including 2055 Crohn’s patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3–33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn’s disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous. Conclusions There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn’s disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.

Abstract Background and Aims To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC]. Methods Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N = 1162, induction] and W40 [LUCENT-2: N = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR. Results Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [p <0.001], irrespective of prior biologic/tofacitinib failure [p <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [p <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [p <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [p <0.05]; ER at W12 was associated with clinical remission [CR] [p <0.05] and corticosteroid-free remission [CSFR] at W40 [p = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [p <0.05]. Conclusions Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092.

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). These post hoc analyses assessed associations between C-reactive protein (CRP), partial Mayo score (PMS), and efficacy outcomes during tofacitinib induction in UC. Methods Patients received tofacitinib 10 mg twice daily (BID) in an 8-week, phase 2 induction study and 2 identical, 8-week, phase 3 induction studies (OCTAVE Induction 1&2); induction nonresponders (IndNR) received an additional 8 weeks of tofacitinib 10 mg BID in an open-label, long-term extension study. Associations between CRP and PMS, and efficacy outcomes (clinical response, clinical remission, endoscopic improvement, and endoscopic remission) were analyzed using univariate and multivariable logistic regression and receiver operating characteristic curves. Results Changes from baseline in the logarithm of CRP ([log]CRP) and PMS at week 4 were associated with clinical response at week 8 (univariate: per unit, odds ratio [OR], 0.55 [95% confidence interval (CI), 0.48-0.62]; and 0.42 [0.37-0.47], respectively). Among IndNR, change from baseline in PMS at week 8 was associated with clinical response at week 16 (univariate: per unit, OR, 0.59; 95% CI, 0.46-0.75). C-reactive protein at week 4 (area under the curve [AUC] > 0.6) and PMS at weeks 2 and 4 (AUC, > 0.7) generally exhibited predictive value for week 8 efficacy outcomes. Conclusions Patients who achieved clinical response at week 8 had larger decreases in CRP and PMS at week 4 than patients who did not. IndNR who achieved clinical response at week 16 with extended tofacitinib induction had a larger decrease in PMS at week 8 vs those who did not. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01470612.

AbstractIntroductionMicroscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence‐based guidelines to improve the medical care of patients suffering from this disorder.MethodsGuidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method.ResultsThese guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence‐based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice.ConclusionThese guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.