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Abstract Background Research has shown that fecal biomarkers are useful to assess the activity of inflammatory bowel disease (IBD). The aim of the study is: to evaluate the efficacy of the fecal lactoferrin and calprotectin as indicators of inflammatory activity. Findings A total of 78 patients presenting inflammatory bowel disease were evaluated. Blood tests, the Crohn's Disease Activity Index (CDAI), Mayo Disease Activity Index (MDAI), and Crohn's Disease Endoscopic Index of Severity (CDEIS) were used for the clinical and endoscopic evaluation. Two tests were performed on the fecal samples, to check the levels of calprotectin and lactoferrin. The performance of these fecal markers for detection of inflammation with reference to endoscopic and histological inflammatory activity was assessed and calculated sensitivity, specificity, accuracy. A total of 52 patient's samples whose histological evaluations showed inflammation, 49 were lactoferrin-positive, and 40 were calprotectin-positive (p = 0.000). Lactoferrin and calprotectin findings correlated with C-reactive protein in both the CD and UC groups (p = 0.006; p = 0.000), with CDAI values (p = 0.043; 0.010), CDEIS values in DC cases (p = 0,000; 0.000), and with MDAI values in UC cases (p = 0.000). Conclusion Fecal lactoferrin and calprotectin are highly sensitive and specific markers for detecting intestinal inflammation. Levels of fecal calprotectin have a proportional correlation to the degree of inflammation of the intestinal mucosa.

Background and Aims: Infections are a safety concern in patients with ulcerative colitis [UC]. Etrasimod is an oral, once daily [QD], selective sphingosine 1-phosphate [S1P]1,4,5 receptor modulator for the treatment of moderately to severely active UC. It leads to selective and reversible lymphocyte sequestration and partial peripheral lymphocyte count decrease. We report infection events from the phase 3 ELEVATE programme., Methods: Proportions, incidence rates [IRs; per 100 patient-years], and descriptive analyses of all serious, severe, herpes zoster and opportunistic infections are reported in the Pivotal UC cohort [ELEVATE UC 52 and ELEVATE UC 12]. Cox regression models evaluated potential baseline risk factors., Results: In this analysis [n = 787], proportions [IRs] of all infection events were similar for patients receiving etrasimod 2 mg QD (18.8% [41.1]) or placebo (17.7% [49.0]). Serious infections occurred in three [0.6%] and five [1.9%] patients receiving etrasimod and placebo, respectively. Two herpes zoster events were reported in each group [etrasimod: 0.4%; placebo: 0.8%], all localised and non-serious. One opportunistic infection event was reported in each group. No patient with an absolute lymphocyte count [ALC] < 0.2 × 109/L reported serious/severe or opportunistic infections; no baseline risk factors were identified for such events. No deaths occurred., Conclusions: Patients receiving etrasimod demonstrated no increased risk of infection. The incidence of serious infections and herpes zoster was similar in each group. Among patients receiving etrasimod, no association between ALC < 0.5 × 109/L and infection events was observed. Longer-term follow-up will further characterise the etrasimod safety profile. Clinicaltrials.gov: NCT03945188; NCT03996369., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries., Methods: Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded., Results: In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications., Conclusions: Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively interferes with the quality of life of the patients, on a physical, emotional, and social level. Its symptoms can vary including diarrhea, bleeding, abdominal pain, fever, and weight loss, depending on the type and location and severity of the disease. Despite evolving treatment, they do not always achieve control of the symptoms, so between 23% and 45% of people with idiopathic chronic ulcerative colitis, and up to 75% of those with Crohn's disease, eventually, will need surgery., Objective: The increase in its incidence in Latin America has promoted a renewed interest on the part of the medical and scientific community in standardizing and unifying criteria for the proper diagnosis and management of the disease, which is part of the current discussions of various events; however, this interest has not yet been reflected in policies and initiatives by governments to address the disease. We decided to develop a consensus meeting in order to elucidate the actual situation of IBD care in our region., Design: The methodology employed to build the consensus document derived from a review of literature, evidence, and policies on IBD, followed by a process of validation and feedback with a group of 10 experts in the field., Methods: Nine experts from different countries in Latin America were reunited in web meetings on 2 days and voted on topics derived from the consensus document. A full agreement with 100% approval was needed, so topics were discussed to reach the consensus otherwise were removed., Results: There is still a lack of information about IBD in Latin America, therefore IBD continues to be an 'invisible' disease and is little recognized by decision-makers., Conclusion: This document describes the current situation of IBDs in the Latin American region, highlighting the main barriers and challenges in timely access to diagnosis and treatment, in order to demonstrate the need to promote the development and implementation of policies, in order to improve the quality of care of patients with IBD., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background: In real-world experience, the number of patients using vedolizumab as first-line biological therapy was low. We aimed to evaluate the effectiveness and safety of vedolizumab in mild-to-moderate Crohn's disease (CD) biologic-naïve patients., Methods: We performed a retrospective multicentric cohort study with patients who had clinical activity scores (Harvey-Bradshaw Index [HBI]) measured at baseline and weeks 12, 26, 52, as well as at the last follow-up. Clinical response was defined as a reduction ≥3 in HBI, whereas clinical remission as HBI ≤4. Mucosal healing was defined as the complete absence of ulcers in control colonoscopies. Kaplan-Meier survival analysis was used to assess the persistence with vedolizumab., Results: From a total of 66 patients, 53% (35/66) reached clinical remission at week 12. This percentage increased to 69.7% (46/66) at week 26, and 78.8% (52/66) at week 52. Mucosal healing was achieved in 62.3% (33/53) of patients. Vedolizumab was well tolerated, and most adverse events were minor. During vedolizumab treatment, 3/66 patients underwent surgery., Conclusions: This study demonstrates the effectiveness and safety of vedolizumab as a first-line biological agent in patients with mild-to-moderate CD., Competing Interests: P.G.K. and N.S.F.Q. hold the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. A.Z.D. received a funding to a Master’s Degree scholarship for 2 years. D.O.M., E.G.V., M.M.L., R.L.P., R.L.K.J., and M.A.G.F. have nothing to declare. J.M.F.C. served as speaker for Abbott, Abbvie, Janssen and Takeda. LAC e ARA served as speaker for Janssen, Takeda, Abbvie. F.S. served as Advisory board member of Eurofarma, Janssen, Pfizer, Takeda, and speaker for AbbVie, Amgen, Ferring, Janssen, Pfizer, Sandoz, and Takeda. M.A. served as speaker from Janssen, Takeda, Abbvie, and Pfizer. NSC served as speaker from Janssen, Abbvie, and Sandoz. J.M.L.P. and J.C.L. served as speaker for Takeda. R.S.P. received lecture fee[s] from AbbVie, Janssen, Takeda, Pfizer; is an advisory committee member for Janssen and AbbVie; and he also does clinical research for Janssen and Abbvie. C.F. served as speaker from Takeda, Abbvie, Janssen, Sandoz, Pfizer. E.M.M. served as speaker from Takeda, Janssen, and Ferring. S.C.F. and G.M.N. served as speaker for Takeda and Janssen. N.S.F.Q. served a speaker and advisory board member for Janssen, Takeda, and Abbvie. P.G.K. served as speaker and consultancy for Janssen, Takeda, Abbvie, and Pfizer., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis [UC]. We evaluated the relationship between Mayo/Inflammatory Bowel Disease Questionnaire [IBDQ] scores and Work Productivity and Activity Impairment-UC [WPAI-UC] components in patients with UC., Methods: All available pooled data from three Phase 3 tofacitinib studies [OCTAVE Induction 1 and 2 and OCTAVE Sustain] were included. Relationships were estimated using repeated measures regression models with Mayo score/subscores or IBDQ total/domain scores as a separate anchor predictor and WPAI-UC components as the outcome., Results: Evidence for linear relationships was confirmed between Mayo/IBDQ scores and WPAI-UC components. Robust relationships between total Mayo score/IBDQ total score and WPAI-UC presenteeism, work productivity loss, and activity impairment were observed; relationships with absenteeism were weak. Total Mayo scores of 0 and 12 corresponded, on average, to WPAI-UC component scores of < 15% and ≥ 60%, respectively, and IBDQ total scores of 224 and 32 corresponded, on average, to WPAI-UC component scores of < 6% and ≥ 90%, respectively. Presenteeism, work productivity loss, and activity impairment [all 0-100%], respectively, improved on average by 14.7, 13.6, and 16.4 percentage points for every 3-point improvement in total Mayo score, and by 8.1, 7.9, and 8.8 percentage points for every 16-point improvement in IBDQ total score., Conclusion: Robust relationships between Mayo/IBDQ scores with WPAI-UC presenteeism, work productivity loss, and activity impairment suggest that patient productivity and non-work activities are strongly associated with disease activity and HRQoL. The weak relationships with absenteeism suggest that patients attend work regardless of their disease activity/poor HRQoL. ClinicalTrials.gov: NCT01465763;NCT01458951;NCT01458574., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We evaluated tofacitinib efficacy and safety in the 52-week maintenance study, OCTAVE Sustain, by baseline Mayo endoscopic subscore (MES) following 8-week induction., Methods: The proportion of patients achieving efficacy endpoints at Week 24 or 52 of OCTAVE Sustain was evaluated by baseline MES following 8-week induction. Using logistic regression, the difference in treatment effect (tofacitinib vs. placebo) between baseline MES (0 vs. 1) for each endpoint was assessed. Adverse events were evaluated., Results: At Week 52 of OCTAVE Sustain, a numerically higher proportion of tofacitinib-treated patients achieved remission with OCTAVE Sustain baseline MES of 0 versus 1 (61.9% vs. 36.5% for tofacitinib 5 mg twice daily [BID] and 75.0% vs. 54.2% for tofacitinib 10 mg BID). Similar trends were observed for endoscopic remission and endoscopic improvement. Logistic regression analyses showed a larger treatment effect at Week 52 in patients with baseline MES of 0 versus 1 for clinical response (p = 0.0306) in the tofacitinib 5 mg BID group (other endpoints all p > 0.05); differences were not significant for any endpoint in the 10 mg BID group (all p > 0.05). Infection adverse events were less frequent among patients with baseline MES 0 versus 1., Conclusions: MES may be important in predicting long-term efficacy outcomes for tofacitinib maintenance treatment. Aiming for endoscopic remission during induction with tofacitinib 10 mg BID may allow successful maintenance with tofacitinib 5 mg BID. Safety was consistent with the known tofacitinib safety profile. Trial registration NCT01458574., (© 2023. The Author(s).)

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., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease which affects the colorectal mucosa with a relapsing-remitting pattern. The therapeutic options currently available for the medical management of UC include many options. Tofacitinib is an oral small molecule, Janus kinase (JAK) inhibitor, more selective for JAK1 and JAK3, which reduces the inflammatory process involved in the pathogenesis of UC., Methods: Retrospective observational multicentric study of patients with UC who used tofacitinib in any phase of their treatment. Clinical remission and response (according to Mayo score), mucosal healing, primary and secondary loss of response, discontinuation of the drug with possible causes, and the need for dose optimization or switching to biologicals, need for surgery and adverse events were evaluated., Results: From a total of 56 included patients, clinical remission was observed in 43.6% at week 12, 54.5% at week 26, 57.9% at week 52, and 40% at the last follow-up visit. Clinical response was observed in 71.4%, 81.8%, 89.5%, and 61.8% at the same time periods, respectively. Mucosal healing rates were 50% and 17.8% needed colectomy., Conclusions: Tofacitinib was effective in induction and maintenance of clinical response and remission rates, compatible to other international real-word studies and meta-analyses., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Cases of coronavirus disease 2019 (COVID-19) have emerged in discrete waves. We explored temporal trends in the reporting of COVID-19 in inflammatory bowel disease (IBD) patients., Methods: The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry of IBD patients diagnosed with COVID-19. The average percent changes (APCs) were calculated in weekly reported cases of COVID-19 during the periods of March 22 to September 12, September 13 to December 12, 2020, and December 13 to July 31, 2021., Results: Across 73 countries, 6404 cases of COVID-19 were reported in IBD patients. COVID-19 reporting decreased globally by 4.2% per week (95% CI, -5.3% to -3.0%) from March 22 to September 12, 2020, then climbed by 10.2% per week (95% CI, 8.1%-12.3%) from September 13 to December 12, 2020, and then declined by 6.3% per week (95% CI, -7.8% to -4.7%). In the fall of 2020, weekly reporting climbed in North America (APC, 11.3%; 95% CI, 8.8-13.8) and Europe (APC, 17.7%; 95% CI, 12.1%-23.5%), whereas reporting was stable in Asia (APC, -8.1%; 95% CI, -15.6-0.1). From December 13, 2020, to July 31, 2021, reporting of COVID-19 in those with IBD declined in North America (APC, -8.5%; 95% CI, -10.2 to -6.7) and Europe (APC, -5.4%; 95% CI, -7.2 to -3.6) and was stable in Latin America (APC, -1.5%; 95% CI, -3.5% to 0.6%)., Conclusions: Temporal trends in reporting of COVID-19 in those with IBD are consistent with the epidemiological patterns COVID-19 globally., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background & Aims: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults., Methods: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters., Results: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life., Conclusions: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Crohn's disease (CD) is a chronic inflammatory disease with a complex interface of broad factors. There are two main treatments for Chron's disease: biological therapy and nonbiological therapy. Biological agent therapy (e.g., anti-TNF) is the most frequently prescribed treatment; however, it is not universally accessible. In fact, in Brazil, many patients are only given the option of receiving nonbiological therapy. This approach prolongs the subsequent clinical relapse; however, this procedure could be implicated in the immune response and enhance disease severity. Our purpose was to assess the effects of different treatments on CD4 + T cells in a cohort of patients with Crohn's disease compared with healthy individuals. To examine the immune status in a Brazilian cohort, we analyzed CD4 + T cells, activation status, cytokine production, and Treg cells in blood of Crohn's patients. Patients that underwent biological therapy can recover the percentage of CD4 + CD73 + T cells, decrease the CD4 + T cell activation/effector functions, and maintain the peripheral percentage of regulatory T cells. These results show that anti-TNF agents can improve CD4 + T cell subsets, thereby inducing Crohn's patients to relapse and remission rates., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Eliane Aparecida Rosseto-Welter et al.)

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we report steroid-free efficacy and safety with tofacitinib among patients with UC who received corticosteroids at baseline of the maintenance study (OCTAVE Sustain)., Methods: This analysis included patients with clinical response following OCTAVE Induction 1 and 2 who were re-randomized to receive placebo, or tofacitinib 5 or 10 mg twice daily (b.d.), in OCTAVE Sustain for 52 weeks and were receiving corticosteroids at OCTAVE Sustain baseline. Corticosteroid tapering was mandatory during OCTAVE Sustain. Rates of steroid-free remission, endoscopic improvement, and clinical response were assessed, stratified by baseline characteristics. Adverse events (AEs) were stratified by treatment and steroid-free remission status., Results: Overall, 289/593 patients had corticosteroid use at OCTAVE Sustain baseline. At week 52, steroid-free remission, endoscopic improvement, and clinical response rates were 10.9%, 11.9%, and 17.8% among patients receiving placebo, 27.7%, 29.7%, and 40.6% among patients receiving tofacitinib 5 mg b.d., and 27.6%, 29.9%, and 43.7% among patients receiving tofacitinib 10 mg b.d., respectively (non-responder imputation; all p  < 0.05 tofacitinib 5 or 10 mg b.d. versus placebo). Discontinuations due to AEs were lower among patients with steroid-free remission versus without. AEs of special interest were infrequent., Conclusion: For patients with baseline corticosteroid use in OCTAVE Sustain, the odds of achieving steroid-free efficacy endpoints were significantly higher for tofacitinib versus placebo, irrespective of tofacitinib dose. There were no apparent differences in AEs of special interest by steroid-free remission status.ClinicalTrials.gov: NCT01458574., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.R.V. has received consulting fees and unrestricted research grants from Abbott, Falk Pharma GmbH, Ferring Pharmaceuticals, Janssen, MSD, Pfizer Inc, Sanofi-Aventis, Takeda, Tillotts, UCB, and Vifor. T.G. has a consultancy contract with Sanofi-Aventis; has received a travel grant from Falk Pharma GmbH and Vifor; and has an unrestricted research grant from Novartis. B.L.C. has served as an advisory board member for and received consulting fees from AbbVie, Celgene-Bristol-Myers Squibb, Pfizer Inc, Sublimity Therapeutics, and TARGET RWE; fees from the CME companies, Cornerstones, and Vindico; and has received speaker fees from AbbVie. W.R. has received research grants from Abbott, AbbVie, AESCA, Centocor, Dr. Falk Pharma, Immundiagnostik, and MSD; lecture fees from Abbott, AbbVie, AESCA, Aptalis, Celltrion, Centocor, Danone, Dr. Falk Pharma, Elan, Ferring Pharmaceuticals, Immundiagnostik, Mitsubishi Tanabe Pharma, MSD, Otsuka, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; and consulting fees from Abbott, AbbVie, AESCA, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia Biologics, Bioclinica, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cellerix, Celltrion, Centocor, ChemoCentryx, Covance, Danone, Dr. Falk Pharma, Elan, Ferring Pharmaceuticals, Galapagos, Genentech, Gilead Sciences, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson and Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma, MSD, Nestlé, Novartis, Ocera, Otsuka, PDL, Pfizer Inc, Pharmacosmos, Procter & Gamble, Prometheus Laboratories, Robarts Clinical Trials, Schering-Plough, Second Genome, SetPoint Medical, Takeda, Therakos, TiGenix, UCB, Vifor, Zyngenia, and 4SC. F.S. has served as an advisory board member for Pfizer Inc and has received consulting and speaker fees from AbbVie, Eurofarma, Ferring Pharmaceuticals, Janssen, Sandoz, Takeda, and UCB. M.F., X.G., and N.L. are employees and shareholders of Pfizer Inc. J.P. is an employee of Syneos Health, which was a paid contractor to Pfizer in connection with the development of this manuscript and related statistical analysis. L.P.-B. has received honoraria from AbbVie, Allergan, Alma, Amgen Biogen, Arena, Boehringer Ingelheim, Celgene, Celltrion, Enterome, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Hikma, Index Pharmaceuticals, Janssen, MSD, Nestlé, Pfizer Inc, Pharmacosmos, Roche, Samsung Bioepis, Sandoz, Sterna, Takeda, and Tillotts; grants from AbbVie, MSD, and Takeda; and is a stockholder of CTMA., (© The Author(s), 2022.)

Background: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD., Methods: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed., Results: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time., Conclusions: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents., (© 2022. The Author(s).)

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies., Competing Interests: Declaration of interests LGu reports consulting fees from AbbVie. RP reports consulting fees from AbbVie, Abbott, Alimentiv (formerly Robarts Clinical Trials), Amgen, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pandion, Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Satisfai Health, Sandoz, Schering-Plough, Shire, Sublimity Therapeutics, Theravance Biopharma, Union Chimique Belge, and Takeda Pharmaceuticals; and research support from AbbVie, Ferring, Janssen, Pfizer, and Takeda. WJS reports research grants from AbbVie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and Theravance Biopharma; consulting fees from AbbVie, Abivax, Admirx, Alfasigma, Alimentiv Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; and stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Prometheus Laboratories, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences. MAl has served as a speaker, consultant, and advisory board member for Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Genentech IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, and Tillotts. ANA has served as an advisory board member for AbbVie, Gilead Sciences, Sun Pharma, and Ikena Therapeutics, and is supported by research funding from the Chleck Family Foundation, Crohn's and Colitis Foundation, and the National Institutes of Health. PGK reports speaking and consultancy honoraria from AbbVie, Janssen, Ferring, Pfizer, Takeda, and Novartis, and scientific grants from Pfizer and Takeda. IEK has served as an advisory board member for AbbVie, Astelas, Genesis, Janssen, Merck Sharp & Dohme, Pharmacosmos, Pfizer, Shire, and Takeda; as a speaker for AbbVie, Astelas, Genesis, Janssen, Merck Sharp & Dohme, and Takeda; and has received research support from AbbVie, Ferring, and Vifor Pharma. PLL has served as a speaker and advisory board member for AbbVie, Amgen, Arena Pharmaceuticals, Fresenius Kabi, Genetech, Gilead Sciences, Janssen, Merck, Mylan, Pharmacosmos, Pfizer, Roche, Takeda, Tillots, and Viatris; and has received unrestricted research grants from AbbVie, Takeda, and Pfizer. JOL reports honoraria for developing and delivering the Cornerstones Health Best of DDW program; funding from AbbVie, Celgene, Gilead Sciences, Janssen, Pfizer, Takeda, and Tillots; additional research support from AbbVie, Gilead Sciences, Pfizer, Shire, and Takeda; consultancy fees from AbbVie, Allergan (Warner Chilcott), Atlantic Healthcare, Bristol Myers Squibb, Celgene, Celtrion, Ferring, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck Sharp & Dohme, Napp, Norgine, Pfizer, Shire, Takeda, and Vifor Pharma, and speaking fees and travel support from AbbVie, Allergan (Warner Chilcott), Ferring, Janssen, Merck Sharp & Dohme, Napp, Norgine, Pfizer, Shire, Tillotts, and Takeda. FM has served as a speaker for, and has received honoraria from, AbbVie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratorios Vitoria, Lilly, Merck Sharp & Dohme, Pfizer, Takeda, Sandoz, UCB, and Vifor Pharma. GJM has served as advisory board member for AbbVie, Celgene, Celtrion, Ferring, Genesis, Hospira, Janssen, Millennium Pharmaceuticals, Merck Sharp & Dohme, Mylan, Pharmacosmos, Pfizer, Takeda, and Vianex; has served as a speaker for AbbVie, Angelini, Falk Pharma, Ferring, Galenica, Cenesis, Hospira, Janssen, Merck Sharp & Dohme, Omega Pharma, Takeda, and Vianex; has served as a consultant for Merck Sharp & Dohme and Takeda; and has received research support from AbbVie, Galenica, Genesis, Menarini Group, and Merck Sharp & Dohme. SCN reports research grants and speaker honoraria from Takeda, Ferring, AbbVie, Janssen, and Tillotts. JP has received research grants from AbbVie and Pfizer; speaker's fees from AbbVie, Ferring, Janssen, Pfizer, and Takeda; and has been a consultant for AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Genentech, GlaxoSmithKline, Janssen, Origo, Pandion, Pfizer, Progenity, Alimentiv (formerly Robarts Clinical Trials), Roche, Takeda, Theravance, and Wassermann. GR has consulted for AbbVie, Augurix, Bristol Myers Squibb, Boehringer, Calypso, Celgene, Falk, Ferring, Fisher, Genentech, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Phadia, Roche, UCB, Takeda, Tillotts, Vifor Pharma, Vital Solutions, and Zeller; has received speaker's honoraria from AstraZeneca, AbbVie, Falk, Janssen, Merck Sharp & Dohme, Pfizer, Phadia, Takeda, Tillotts, UCB, Vifor Pharma, and Zeller; and has received educational grants and research grants from AbbVie, Ardeypharm, Augurix, Calypso, FALK, Flamentera, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Tillotts, UCB, and Zeller. FS has served as a speaker and consultant for AbbVie, Amgen, Ferring, Janssen, Pfizer, Sandoz, Takeda, and UCB. AD has served as a speaker, consultant, and advisory board member for Merck Sharp & Dohme, AbbVie, Janssen, Roche/Genentech, Ferring, Tillotts, Vifor Pharma, Pharmacosmos, Pfizer, Celltrion, Takeda, Boehringer Ingelheim, Amgen, Sandoz, Bristol Myers Squibb/Celgene, Otsuka, Biogen, Gilead/Galapagos, Fresenius Kabi, and Arena Pharmaceuticals. BES reports consulting fees from 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Capella Biosciences, Celgene, Celltrion Healthcare, EnGene, Ferring, Genentech, Gilead Sciences, Hoffmann-La Roche, Immunic, Ironwood Pharmaceuticals, Janssen, Lilly, Lyndra, MedImmune, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, RedHill Biopharma, Rheos Medicines, Seres Therapeutics, Shire, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, TiGenix, and Vivelix Pharmaceuticals; honoraria for speaking in continuing medical education programmes from Takeda, Janssen, Lilly, Gilead Sciences, Pfizer, and Genentech; and research funding from Celgene, Pfizer, Takeda, Theravance Biopharma R&D, and Janssen. SD has served as a speaker, consultant, and advisory board member for Schering-Plough, Abbott (AbbVie) Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millennium Takeda, Nycomed, Pharmacosmos, Actelion, A Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor Pharma, and Johnson & Johnson. LP-B has served as a speaker, consultant, and advisory board member for Merck, AbbVie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor Pharma, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boehringer Ingelheim, Lilly, HAC Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma, Celgene, Biogen, Lycera, Samsung Bioepis, and Theravance. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aim: One of the most impacted regions by the pandemic globally, Latin America is facing socioeconomic and health-care challenges that can potentially affect disease outcomes. Recent data suggest that inflammatory bowel disease (IBD) patients do not have an increased risk of the development of COVID-19 complications. However, the impact of COVID-19 on IBD patients living in least developed areas remains to be fully elucidated. This study aims to describe the outcomes of IBD patients diagnosed with COVID-19 in countries from Latin America based on data from the SECURE-IBD registry., Methods: Patients from Latin America enrolled in the SECURE-IBD registry were included. Descriptive analyses were used to summarize clinical and sociodemographic characteristics. The studied outcomes were (i) a composite of need for intensive care unit admission, ventilator use, and/or death (primary outcome) and (ii) a composite of any hospitalization and/or death (secondary outcome). Multivariable regression was used to identify risk factors of severe COVID-19., Results: During the study period, 230 cases (Crohn's disease: n = 115, ulcerative colitis: n = 114, IBD-unclassified [IBD-U]: n = 1) were reported to the SECURE-IBD database from 13 different countries. Primary outcome was observed in 17 (7.4%) patients, and the case fatality rate was 1.7%. In the adjusted multivariable model, the use of systemic corticosteroids (odds ratio [OR] 10.97; 95% confidence interval [CI]: 3.44-34.99) was significantly associated with the primary outcome. Older age (OR 1.03; 95% CI: 1.00-1.05), systemic corticosteroids (OR 9.33; 95% CI: 3.84-22.63), and the concomitant presence of one (OR 2.14; 95% CI: 0.89-5.15) or two (OR 10.67; 95% CI: 1.74-65.72) comorbidities were associated with the outcome of hospitalization or death., Conclusion: Inflammatory bowel disease patients with COVID-19 in Latin America appear to have similar outcomes to the overall global data. Risk factors of severe COVID-19 are similar to prior reports., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)