Preventing and managing cardiovascular events in patients with inflammatory bowel diseases treated with small-molecule drugs, an international Delphi consensus.

Janus kinase (JAK) inhibitors and sphingosine 1 phosphate (S1P) receptor modulators are small molecule drugs (SMDs) approved for IBD treatment. Their use in clinical practice might be limited due to cardiovascular concerns. We aimed to provide guidance on risk assessment, monitoring, and management strategies, aiming to minimize potential cardiovascular risks of SMDs and to facilitate an adequate shared decision-making. A systematic literature search was conducted, and proposed statements were prepared. A virtual consensus meeting was held, in which eleven IBD physicians and two cardiovascular specialists from ten countries attended. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75 % of participants voting as 'agree' with each statement. Consensus was reached for eighteen statements. Available evidence does not show a higher risk of cardiovascular events with JAK inhibitors in the overall IBD population, although it might be increased in patients with an unfavorable cardiovascular profile. S1P receptor modulators may be associated with a risk of bradycardia, atrioventricular blocks, and hypertension. Cardiovascular risk stratification should be done before initiation of SMDs. Although the risk of cardiovascular events in patients with IBD on SMDs appears to be low overall, caution should still be taken in certain scenarios.

Association Between Smoking Status and the Efficacy and Safety of Tofacitinib in Patients with Ulcerative Colitis.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This analysis assessed the impact of cigarette smoking on tofacitinib efficacy and safety in the UC clinical program. Methods: Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in the phase (P)2 induction study (baseline demographics and safety only), P3 studies (OCTAVE Induction 1&2, OCTAVE Sustain, OCTAVE Open), and P3/4b RIVETING study. Results: This post hoc analysis included 1156 patients (ever smokers, n = 416 [36.0%; current smokers, n = 59 (5.1%); ex-smokers, n = 357 (30.9%)]; never smokers, n = 740 [64.0%]; median [range] treatment duration 654 [1-2712] and 615.5 [1-2850] days, respectively). Similar proportions of ever smokers and never smokers achieved efficacy endpoints. AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection (serious infections, 5.5%; herpes zoster [nonserious and serious], 10.8%; Clostridioides difficile infection, 12.0%; lower respiratory tract infection, 19.5%: corresponding values among never smokers were 53.1%, 3.9%, 6.8%, 8.5%, and 11.4%). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers and thromboembolism events (venous and arterial) in 1.0% of ever smokers and 0.9% never smokers. Deaths, malignancies (excluding non-melanoma skin cancer [NMSC]), and NMSC occurred infrequently in ever smokers (0.5%, 2.5%, and 3.7%, respectively) and never smokers (0.1%, 1.5%, and 1.0%, respectively). Colorectal cancer was reported in 0.6% of never smokers; no cases occurred in ever smokers. Conclusions: Efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. Overall, serious AEs and, as expected, infections were more frequent in ever smokers versus never smokers. This may inform treatment selection and monitoring strategies. ClinicalTrialsgov: NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304.

Correlation between trough levels of infliximab and postoperative endoscopic recurrence in Crohn's disease patients submitted to ileocolonic resections.

OBJECTIVES: The aim of this study was to evaluate serum levels of Infliximab (IFX) in patients with Crohn's disease (CD) who underwent an ileocolonic resection and to correlate them with the presence or absence of endoscopic disease recurrence. METHODS: An observational and cross-sectional study was carried out in patients from 2 treatment centers in Curitiba-PR, with CD, who underwent ileocaecal resection and used IFX after surgery. Drug serum levels were measured, and colonoscopy was performed 30 days before or after collection. Patients were then divided into two groups: with or without endoscopic recurrence (defined as a Rutgeerts score greater than or equal to 2), and mean serum IFX levels were identified and compared. The primary objective was the correlation between recurrence and the median levels of IFX, performed comparatively between groups. RESULTS: Of the 21 patients included in the study, 14 had no endoscopic recurrence and 7 had it. There was no difference between groups in terms of baseline patient characteristics, mono or combo therapy treatment, serum albumin, and the time elapsed between collection of serum levels and diagnosis, surgery, and beginning of therapy. Patients with endoscopic recurrence used more biologics previously ( P  = 0.027). There was no difference between the median values of serum IFX levels between the groups: (4.71 [0.03-14.4]) in patients without recurrence versus (2.18 [0.88-14]) in those with recurrence ( P  = 0.601). CONCLUSION: Low serum IFX levels were not correlated with postoperative endoscopic recurrence. Studies with a larger number of patients are needed to better test the proposed hypothesis.

Presence of risk factors associated with colectomy among patients with ulcerative colitis: a post hoc analysis of data from the tofacitinib OCTAVE ulcerative colitis clinical program.

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Objective: To assess colectomy incidence rates (IRs) and baseline characteristics for the presence of identified colectomy risk factors among patients in the tofacitinib OCTAVE UC clinical program. Design: This post hoc analysis evaluated patients in the 8-week OCTAVE Induction 1 and 2, 52-week OCTAVE Sustain, and OCTAVE Open (open-label, long-term extension) studies. Methods: IRs [95% confidence interval (CI)] for colectomy were analyzed. Baseline risk factors based on clinical guidelines: aged <40 years at diagnosis, extensive colitis, severe endoscopic disease [Mayo endoscopic subscore (MES) = 3], hospitalization for UC within 12 months, C-reactive protein (CRP) >3 mg/L, and serum albumin <3.5 g/dL. Baseline risk factors were evaluated in patients who underwent colectomy by study and summarized descriptively. Results: Over a maximum of 7.8 years of tofacitinib exposure, 14 patients underwent colectomy: 3/1139 (0.3%) in OCTAVE Induction 1 and 2 [tofacitinib 10 mg twice daily (BID): n = 2; placebo: n = 1], 3/593 (0.5%) in OCTAVE Sustain (placebo: n = 3), and 8/944 (0.8%) in OCTAVE Open (tofacitinib 10 mg BID: n = 8). Colectomy IR per 100 patient-years for all patients who received ⩾1 tofacitinib dose was 0.34 (95% CI: 0.16-0.63). All patients who underwent colectomy had ⩾1 risk factor and prior tumor necrosis factor inhibitor (TNFi) failure, among which the most common risk factors were a MES of 3 (n = 13), CRP >3 mg/L (n = 11), and aged <40 years at diagnosis (n = 9). Conclusions: Among patients with moderate to severe UC receiving tofacitinib, colectomies were infrequent; all patients undergoing colectomy had prior TNFi failure, and most had multiple additional risk factors. This provides important information to discuss with patients and inform management decisions. Registration: NCT01465763; NCT01458951; NCT01458574; and NCT01470612.

Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.

The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD).

INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.

Management of pouch neoplasia: consensus guidelines from the International Ileal Pouch Consortium.

Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise.

New insights on the surgical management of ulcerative colitis in the 21st century.

Despite substantial advances in medical therapy since 2005 that have led to the approval and increased use of novel biological agents and small molecules, colectomy is still a therapeutic option for some patients with ulcerative colitis. In the biological era (ie, after the approval of biological agents for ulcerative colitis), improved control of disease activity has led to a trend of decreasing colectomy rates for refractory disease. Consequently, indications for colectomy for dysplasia and colorectal cancer seem to be increasing. Advances have not only been made in surgical techniques, but also in multidisciplinary approaches, the timing of surgery, and in medical management before and after surgery. This Review discusses surgical indications in patients with ulcerative colitis in relation to current medical therapy, management in the acute setting, indications for staged procedures, new techniques such as transanal surgery and robotics, and surgical alternatives to ileal pouch-anal anastomosis. A multidisciplinary approach including surgeons, gastroenterologists, pathologists, radiologists, and clinical nutritionists is essential to improving patient outcomes in different clinical scenarios of ulcerative colitis management in the 21st century.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

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.

Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives.

Therapeutic drug monitoring (TDM) has emerged as a useful tool for optimising the use of biologics, and in particular anti-tumour necrosis factor (anti-TNF) therapy, in inflammatory bowel disease (IBD). However, challenges remain and are hindering the widespread implementation of TDM in clinical practice. These barriers include identification of the optimal drug concentration to target, the lag time between sampling and results, and the proper interpretation of anti-drug antibody titres among different assays. Solutions to overcome these barriers include the harmonisation of TDM assays and the use of point-of-care testing. Other unmet needs include well designed prospective studies and randomised controlled trials focusing on proactive TDM, particularly during induction therapy. Future studies should also investigate the utility of TDM for biologics other than anti-TNF therapies in both IBD and other immune-mediated inflammatory diseases such as rheumatoid arthritis and psoriasis, and the use of pharmacokinetic modelling dashboards and pharmacogenetics towards individual personalised medicine.

Endpoints for extraintestinal manifestations in inflammatory bowel disease trials: the EXTRA consensus from the International Organization for the Study of Inflammatory Bowel Diseases.

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.

Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review.

BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals <21 years old over the first 2 decades of the 21st century. METHODS: We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn's disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD. RESULTS: A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous. CONCLUSIONS: Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries.

Temporal trends in the epidemiology of inflammatory bowel diseases in the public healthcare system in Brazil: A large population-based study.

Background: Population-based data on epidemiology of Inflammatory Bowel Diseases (IBD) in Brazil are scarce. This study aims to define temporal trends of incidence and prevalence rates of Crohn's disease (CD) and ulcerative colitis (UC) in Brazil. Methods: All IBD patients from the public healthcare national system were included from January 2012 to December 2020. Average Annual Percent Change (AAPC) and 95% confidence intervals (CI) were calculated using log-linear regression for incidence and binomial regression for prevalence. Moran's I autocorrelation index was used to analyse clustering of cities by level of prevalence. Findings: A total of 212,026 IBD patients were included. Incidence of IBD rose from 9.4 in 2012 to 9.6 per 100,000 in 2020 (AAPC=0.8%; 95% CI -0.37, 1.99); for UC, incidence increased from 5.7 to 6.9 per 100,000 (AAPC=3.0%; 95% CI 1.51, 4.58) and for CD incidence decreased from 3.7 to 2.7 per 100,000 (AAPC=-3.2%; 95% CI -4.45, -2.02). Prevalence of IBD increased from 30.0 in 2012 to 100.1 per 100,000 in 2020 (AAPC=14.8%; CI 14.78-14.95); for UC, from 15.7 to 56.5 per 100,000 (AAPC=16.0%; CI 15.94, 16.17); for CD from 12.6 to 33.7 per 100,000 (AAPC=12.1% CI 11.95, 12.02). A south-north gradient was observed in 2020 prevalence rates of IBD [I=0.40 (p<0.0001)], CD [I=0.22 (p<0.0001)] and UC [I=0.42 (p<0.0001)]. Interpretation: Incidence of CD is decreasing whereas of UC is increasing, leading to stabilization in the incidence of IBD from 2012 to 2020 in Brazil. Prevalence of IBD has been climbing with 0.1% of Brazilians living with IBD in 2020. Funding: None.

Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium.

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.

International consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as 'fully agree' or 'mostly agree' with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events.

The impact of body mass index on efficacy and safety in the tofacitinib OCTAVE ulcerative colitis clinical programme.

BACKGROUND: Obesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. AIMS: To assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI). METHODS: This post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8-week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (<25, 25 to <30 and ≥30 kg/m2 ). Outcomes included remission, endoscopic improvement, clinical response, sustained steroid-free remission, Inflammatory Bowel Disease Questionnaire total score and Short Form-36 Health Survey scores. Adverse events were evaluated. RESULTS: At Week 8 of OCTAVE Induction 1 and 2, and Week 52 of OCTAVE Sustain, higher proportions of patients receiving tofacitinib 5 or 10 mg twice daily (b.d.) achieved clinical response vs placebo, regardless of baseline BMI subgroup (all P < 0.05). Proportions of patients achieving efficacy endpoints were generally similar across BMI subgroups; in univariate and multivariate regression analyses, BMI was not a significant predictor (all P ≥ 0.05; univariate BMI [continuous] odds ratio for remission: 0.98 [95% confidence interval 0.95, 1.02]). There was no consistent trend between BMI and adverse events. Among patients receiving tofacitinib 10 mg b.d. in OCTAVE Induction 1 and 2, serious infections were numerically greater in the BMI ≥30 subgroup (3.2%) vs other subgroups (0.4%). Limitations included small patient numbers in the BMI ≥30 subgroup. CONCLUSIONS: Efficacy and safety of tofacitinib were similar in patients with UC regardless of baseline BMI.

COVID-19 outcomes in patients with inflammatory bowel diseases in Latin America: Results from SECURE-IBD registry.

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.

Surgery for Inflammatory Bowel Disease Has Unclear Impact on Female Fertility: A Cochrane Collaboration Systematic Review.

BACKGROUND AND AIMS: Surgical treatment of inflammatory bowel disease (IBD) may impair female fertility. We conducted a systematic review to determine the risk of infertility and pregnancy outcomes in women with IBD who underwent surgery. METHODS: We identified studies evaluating the impact of IBD surgery on infertility and pregnancy outcomes. Risk ratios (RR) and 95% confidence intervals (CIs) were pooled when data were presented using contingency tables. Odds ratios (OR) were pooled when raw numbers were not provided. GRADE was used to evaluate the certainty of evidence. RESULTS: Sixteen observational studies were included, comparing women with and without surgery, open and laparoscopic surgery and before and after surgery. All studies were of low quality. The effect of surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57) was uncertain. Similarly, the fertility effects of laparoscopic versus open surgery method were unclear (RR 0.70, 95% CI 0.38 to 1.27). The impact of IBD surgery on pregnancy outcomes should be interpreted with caution. Surgery was associated with miscarriage (OR 2.03, 95% CI 1.14 to 3.60), use of assisted reproductive technologies (RR 25.09, 95% CI 1.56 to 403.76) and caesarean section (RR 2.23, 95% CI 1.00 to 4.95), but not with stillbirth (RR 1.96, 95% CI 0.42 to 9.18), preterm birth (RR 1.91, 95% CI 0.67 to 5.48), low birth weight (RR 0.61, 95% CI 0.08 to 4.83) or small for gestational age (RR 2.54, 95% CI 0.80 to 8.01). CONCLUSION: The effect of surgical therapy for IBD on rates of female infertility and pregnancy-related outcomes was uncertain due to poor quality of existing literature.

Extraintestinal manifestations at baseline, and the effect of tofacitinib, in patients with moderate to severe ulcerative colitis.

INTRODUCTION: Extraintestinal manifestations (EIMs) in patients with ulcerative colitis (UC) are common. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. We evaluated the efficacy of tofacitinib in patients with EIMs, and the impact of tofacitinib on EIMs in patients with UC in the OCTAVE clinical program. METHODS: Data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain) were analyzed. The effect of tofacitinib on efficacy outcomes stratified by EIM status, proportion of predefined prior and active EIMs at baseline, and change from baseline in EIMs were determined at the end of the treatment period (weeks 8 or 52), or at early termination. RESULTS: At baseline of OCTAVE Induction 1 and 2, and OCTAVE Sustain, 27.0% and 9.0% of patients had a history of EIMs (prior or active), respectively. Patients treated with tofacitinib 10 mg twice daily (BID) achieved remission and had endoscopic improvement in all studies, irrespective of any history of EIMs. A greater proportion of patients had active peripheral arthritis at baseline of OCTAVE Induction 1 and 2 versus OCTAVE Sustain. In OCTAVE Induction 1 and 2, similar proportions of tofacitinib and placebo-treated patients with active peripheral arthritis experienced either no change (81.3% and 85.7%, respectively) or an improvement (15.6% and 14.3%, respectively). By week 52 of OCTAVE Sustain, improvements in active peripheral arthritis were only observed in tofacitinib-treated patients (16.7% and 33.3% with tofacitinib 5 and 10 mg BID, respectively). CONCLUSION: Any history of EIMs did not influence the efficacy of tofacitinib 10 mg BID for induction or maintenance of UC. The most common active EIM was peripheral arthritis, for which many patients in OCTAVE Induction 1 and 2, and OCTAVE Sustain, reported improvement or no change from baseline with tofacitinib treatment.Clinicaltrials.gov:NCT01465763; NCT01458951; NCT01458574.

Adjunctive Hyperbaric Oxygen Therapy in Refractory Crohn's Disease: An Observational Study.

BACKGROUND AND AIMS: Patients may experience complications of Crohn's disease (CD) even when treated with optimal medical therapy strategies. Previous data have shown the efficacy of hyperbaric oxygen therapy (HBOT) in the management of complicated CD. However, there is no consensus regarding the optimal number of sessions or duration of treatment regimens. The aim of the present study was to investigate the efficacy of HBOT in CD patients who were refractory to conventional medical management. METHODS: This study included patients who underwent HBOT for the treatment of the following complications: perianal fistulizing Crohn's disease (pCD), enterocutaneous fistulas (ECF), or pyoderma gangrenosum (PG). Complete healing was defined as the closure of external orifice and the absence of active draining (in pCD), complete wound healing (in PG), and granulation or complete wound epithelialization with no enteric draining (in ECF). The persistence of draining and the absence of wound granulation were defined as incomplete healing. RESULTS: Forty patients were included. The mean CD duration was 10.6 ± 5.8 years. pCD comprised most of the included patients (25/62.5%), followed by ECF (n = 13/32.5%) and PG (n = 6/15%). In two patients (5%), a combination of ECF and PG was diagnosed, and in one patient (2.5%), all three complications were observed. A total of 32 patients (82.5%) had complete healing. Patients with PG had the highest healing rates (100%), followed by those with ECF (84.6%) and pCD (80%). CONCLUSIONS: Adjunctive HBO was associated with significant healing rates for CD-associated complications such as pCD, ECF, and PG.