Early recapture of response with tofacitinib 10 mg twice daily in patients with ulcerative colitis in OCTAVE Open following dose reduction or treatment interruption in OCTAVE Sustain.

BACKGROUND AND AIM: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient-reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance. METHODS: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1-M6 in OCTAVE Open. Changes from baseline in partial Mayo score, rectal bleeding subscore, and stool frequency subscore at M1 were also analyzed, by M2 clinical response status. RESULTS: At M1 of OCTAVE Open, 83.2%, 70.3%, and 64.4% of patients in the retreatment subpopulation (n = 101) had rectal bleeding improvement, stool frequency improvement, and symptomatic improvement, respectively. Corresponding values in the dose escalation subpopulation (n = 57) were 59.6%, 50.9%, and 38.6%. For both subpopulations, results were generally consistent regardless of prior TNFi failure. In the dose escalation subpopulation, mean decrease from baseline in partial Mayo score and stool frequency subscore at M1 was greater in patients with versus without a clinical response at M2. CONCLUSIONS: Rectal bleeding improvement and stool frequency improvement were achieved by M1 in many patients receiving tofacitinib 10 mg BID in both subpopulations, with no apparent difference by prior TNFi failure. Analyses were limited by small sample sizes for some subgroups.

Vedolizumab in Mild-to-Moderate Crohn's Disease Patients Naïve to Biological Therapy: A Multicentric Observational Study.

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.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

Effectiveness and Safety of Tofacitinib in the Management of Ulcerative Colitis: A Brazilian Observational Multicentric Study.

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.

Endoscopic Surveillance in Inflammatory Bowel Diseases: Selecting a Suitable Technology.

In the treat-to-target era, endoscopy has become the backbone of the assessment of remission, defined as mucosal healing, in inflammatory bowel disease (IBD) patients. Current recommendations indicate that endoscopic procedures should be performed with high-definition white-light endoscopy (HD-WLE), as it guarantees the best possible visualization of the mucosa. With respect to endoscopic surveillance, the preventive strategy for dysplasia and colorectal cancer (CRC) in long-standing IBD, is the use of dye-chromoendoscopy (DCE), which enhances the mucosal pattern of the colonic walls. DCE has been established as the gold standard for dysplasia detection and is at present incorporated in all international guidelines. Over the past years, novel technologies, such as high-definition endoscopic imaging, and optical and digital enhancement tools have revolutionized the quality and level of fine details of vascular and mucosal patterns. These endoscopic images have the ambition to reflect histological changes for suspected neoplastic lesions and inflammation or healing and are emerging as potential alternatives to DCE. Indeed, the comparison of DCE with high-definition imaging is an open issue that deserves further investigation. We aimed to examine and summarize the technical aspects and the current evidence on endoscopic technologies with a specific focus on the surveillance in IBD patients.

Gastroenteropancreatic Neuroendocrine Neoplasms in Patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. RESULTS: GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn's disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. CONCLUSIONS: In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis.

Segundo Consenso Brasileiro de Manejo da Doença de Crohn em adultos: um consenso da Organização Brasileira de Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of crohn's disease in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. Objective: To guide the safest and effective medical treatments of adults with CD. Methods: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

RESUMO Contexto: A doença inflamatória intestinal (DII) é uma doença imunomediada que inclui a doença de Crohn (DC) e a retocolite ulcerativa. A DC é caracterizada por um envolvimento intestinal transmural da boca ao ânus com sintomas recorrentes e remitentes que podem levar a danos intestinais progressivos e incapacidade ao longo do tempo. Objetivo: Orientar os tratamentos médicos mais seguros e eficazes de adultos com DC. Métodos: Este consenso foi desenvolvido por autores que representam gastroenterologistas e cirurgiões brasileiros especialistas em doenças colorretais (GEDIIB, Organização Brasileira de Doença de Crohn e Colite). Uma revisão sistemática das evidências mais recentes foi realizada para apoiar as recomendações/declarações. Todas as recomendações e declarações incluídas foram endossadas em um painel Delphi modificado pelas partes interessadas e especialistas em DII com uma concordância de pelo menos 80% ou mais. Resultados e conclusão: As recomendações médicas (intervenções farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso é direcionado a clínicos gerais, gastroenterologistas e cirurgiões interessados em tratar e gerenciar adultos com DC e apoia a tomada de decisões de companhias de seguro de saúde, agências reguladoras e líderes ou administradores de instituições de saúde.

Segundo Consenso Brasileiro no manejo da retocolite ulcerativa em adultos: um consenso da Organização Brasileira para Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of ulcerative colitis in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. Objective: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. Methods: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

RESUMO Contexto: As doenças inflamatórias intestinais são doenças imunomediadas que incluem a doença de Crohn (DC) e a retocolite ulcerativa (RCU). A RCU é uma doença progressiva que acomete a mucosa colorretal causando sintomas debilitantes levando a alta morbidade e incapacidade laboral. Como consequência da inflamação crônica do cólon, a RCU também está associada a um risco aumentado de câncer colorretal. Objetivo: Este consenso visa fornecer orientações sobre o manejo médico mais eficaz de pacientes adultos com RCU. Métodos: As recomendações do consenso foram desenvolvidas por gastroenterologistas e cirurgiões colorretais referências no Brasil (membros da Organização Brasileira para Doença de Crohn e Colite [GEDIIB]). Uma revisão sistemática, incluindo as evidências mais recentes, foi conduzida para apoiar as recomendações. Todas as recomendações foram endossadas pelas partes interessadas/especialistas em doença inflamatória intestinal usando um Painel Delphi modificado. O nível de concordância para alcançar consenso foi de 80% ou mais. Resultados e conclus ão: As recomendações médicas (farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso foi direcionado a clínicos gerais, gastroenterologistas e cirurgiões que tratam pacientes com RCU e apoia os processos de tomada de decisão por companhias de seguro de saúde, agências reguladoras, líderes institucionais de saúde e administradores.

Clinical and Demographic Profile of Inflammatory Bowel Disease Patients in a Reference Center of São Paulo, Brazil.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract with an increasing incidence in developing countries. PURPOSE: To report clinical and demographic data of CD and UC at a referral center for inflammatory bowel disease (IBD) in São Paulo. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study on adult patients with established IBD. Demographic and clinical data were obtained by medical records analysis from the IBD Outpatient Clinic of EPM-UNIFESP, from October 1997 to October 2017. RESULTS: Of 658 patients included, 355 had UC (54%) and 303 had CD (46%). UC was more prevalent in women than CD (219 [61.7%] vs 152 [50.2%], p=0.003). The median time between the onset of symptoms and diagnosis was 13 (5-38) months, with a longer duration for CD patients. CD mostly affected the ileocolonic location (47.9%). CD patients with stricture, fistula and/or perianal disease (213/303, 70.3%) were younger at diagnosis, had a longer disease duration, higher rates of corticosteroid, immunomodulatory, and biological therapy, hospitalization, and referral to surgery, compared to patients without complication. Extensive colitis was the most common extension of UC (50.6%), which was more frequently associated with younger age at diagnosis, hepatobiliary disease, increased need for hospitalization, higher use of immunomodulatory, and biologic therapy, compared to patients with less extensive disease. In the last 5 years, CD patients were more frequently on biologic and/or immunomodulatory (70.9%) therapy, and UC patients often received salicylates (78.1%) and immunomodulatory (28.1%) treatments. There was a consistent reduction in salicylate usage for CD in the last 5 years compared to the total period of follow-up. CONCLUSION: Despite the increasing incidence, we highlight the diagnostic delay and a more complicated CD and extensive UC in this cohort, reflecting a high need for immunomodulatory and biological treatment, hospitalization, and surgery.

TL1A: A New Potential Target in the Treatment of Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory diseases of the gastrointestinal tract. In the last few years, the development of biological agents targeting cytokines and receptors involved in IBD pathogenesis has led to better outcomes and has improved the course of the disease. Despite their effectiveness, drugs such as tumor necrosis factor (TNF) inhibitors, anti-Interleukin-12/23 and anti-integrins, do not induce a response in about one-third of patients, and 40% of patients lose response over time. Therefore, more efficient therapies are required. Recent studies showed that TL1A (Tumor necrosis factor-like cytokine 1A) acts as a regulator of mucosal immunity and participates in immunological pathways involved in the IBD pathogenesis. In this review article, we analyze the role of TL1A as a new potential target therapy in IBD patients.

'Treat to Target' in Mild to Moderate Ulcerative Colitis: Evidence to Support this Strategy.

BACKGROUND: The management of chronic conditions, above all rheumatic disease and diabetes, now incorporates a "treat to target" strategy where treatment aims to achieve objective outcomes. This is applicable in ulcerative colitis (UC) as well. Targets are demonstrated to prevent endorgan dysfunction, specifically bowel damage and its complications, and lastly colorectal cancer. Recently, the scientific community has tried to define further targets beyond those currently recommended, namely mucosal healing and clinical remission. Studies that prospectively investigated this approach in UC are scanty and a treat-to-target (T2T) algorithm is not routinely used in daily clinical practice. OBJECTIVE: We aim to review current evidence on T2T in UC and discuss its adoption in routine clinical practice as well as in clinical trials. METHODS: A PubMed search was conducted in February 2020 to identify published papers investigating targets' achievement rates in UC. RESULTS: Different targets can be achieved through approved drugs for mild to moderate UC; histological remission is emerging as a robust target with respect to long-term outcomes. CONCLUSION: Further studies to compare a T2T strategy with the traditional care are needed, particularly in the mild to moderate spectrum of disease.

Optimizing biologic therapy in IBD: how essential is therapeutic drug monitoring?

Proposed treatment targets for the management of inflammatory bowel disease (IBD) have moved beyond symptomatic improvement towards more objective end points, such as healing of the intestinal mucosa. This treat-to-target approach has been associated with improved disease outcomes such as diminished bowel damage, surgery and hospitalizations. Many patients with IBD require biologic therapy to achieve and maintain clinical and endoscopic remission, and antitumour necrosis factor antibodies remain the first-line biologic therapy in most areas of the world. Unfortunately, up to one-third of patients receiving this treatment are primary non-responders, and some patients that show an initial response can also lose response over time. Therapeutic drug monitoring (TDM) has been suggested as a useful tool to manage patients on antitumour necrosis factor treatment, including monitoring for dose escalation, de-escalation or to switch treatment. In this Perspective, we aim to summarize evidence and guidelines related to TDM in IBD management and also discuss potential strategies to optimize biologic treatment where TDM is not available.

Endoscopy after surgery in inflammatory bowel disease: Crohn's disease recurrence and pouch surveillance.

INTRODUCTION: Crohn's disease (CD) and ulcerative colitis (UC) are immune-mediated disorders characterized by a chronic inflammation, with intermittent exacerbations of symptoms and inflammation. In both diseases, medical treatment has made revolutionary steps forward. Nevertheless, surgery is still required in many cases due to inefficacy of multiple medical therapies. It is not clear whether surgery rates in inflammatory bowel diseases (IBD) are currently decreasing despite all improvements. AREAS COVERED: Multidisciplinary management is critical in surgical patients to improve long-term outcomes. Endoscopy plays a crucial role, both before and after surgery, in planning therapeutic strategies and stratifying risk of recurrence. Aim of this review is to provide a deeper insight into the central role of endoscopy in the postoperative management of IBD patients, focusing on recent research advances, future challenges and unresolved questions. EXPERT OPINION: Both UC and CD surgical patients need endoscopy to define the correct therapeutic choice, predict subsequent disease course and adopt the correct surveillance strategy. In the next future, newer endoscopic techniques could be systematically applied in IBD patients after surgery, to assess early postoperative inflammation, response to treatment, or, regarding UC, to provide enhanced pouch surveillance, allowing for early detection of inflammation and dysplasia.

Treat to target or 'treat to clear' in inflammatory bowel diseases: one step further?

INTRODUCTION: Inflammatory bowel diseases (IBD) are chronic and progressive diseases. Long-term complications are demolitive surgery and colon-rectal cancer. A 'treat to target' strategy, in which the treatment aims to achieve objective outcomes, has already been introduced in the management of chronic conditions as rheumatic diseases. This approach is emerging as suitable for ulcerative colitis and Crohn's disease. Targets are predefined therapeutic goals demonstrated to prevent end-organ dysfunction. An optimization or switch of therapy is considered depending on the target's achievement, with regular monitoring. AREAS COVERED: According to the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) indications, mucosal healing and clinical remission are the main targets in IBDs. Histological remission is increasingly being considered as a novel target and has given rise to the new concept of 'disease clearance' which includes clinical, endoscopic and microscopic remission. We aim to review current evidence on the treat-to-target strategy in comparison to a stricter treat-to-clear in the IBD field. EXPERT OPINION: Prospective studies on treat-to-target algorithm are sparse; a treat-to-clear approach is desirable but far from adoption in the daily practice and clinical trials. The ultimate goals of a treat-to-clear strategy differ in UC and in CD, including histological healing and transmural healing, respectively.

JAK selectivity: more precision less troubles.

INTRODUCTION: Janus kinases inhibitors (JAKi) are new small molecules recently introduced in the armamentarium of treatments for Inflammatory Bowel Disease (IBD). Janus Kinases (JAK) are tyrosine kinases that act by linkage with different intracellular receptors, regulating cytokines gene transcription implicated in the inflammatory burden seen in IBD patients. AREAS COVERED: A comprehensive literature search was performed to retrieve studies on JAKi and IBD to discuss the latest developments and how the selectivity of these drugs is changing the natural course of IBD. EXPERT OPINION: Available data on efficacy and safety of JAKi in IBD are highly encouraging and because of their selectivity, these drugs might become among the foremost options in the treatment algorithm.

Author Correction: Crohn's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Crohn's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: Crohn's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.