Outcomes and Endpoints of Postoperative Recurrence in Crohn's Disease: Systematic Review and Consensus Conference.

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.

Latin America consensus statement inflammatory bowel disease: importance of timely access to diagnosis and treatment.

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.

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.

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.

Biologic Agents in Crohn's Patients Reduce CD4+ T Cells Activation and Are Inversely Related to Treg Cells.

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.

Lifestyle, behaviour, and environmental modification for the management of patients with inflammatory bowel diseases: an International Organization for Study of Inflammatory Bowel Diseases consensus.

Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.

Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn's disease: a real-world multicenter Brazilian study.

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.

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.

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.

Physician Practice Patterns in Holding Inflammatory Bowel Disease Medications due to COVID-19, in the SECURE-IBD Registry.

BACKGROUND: We aimed to describe physician practice patterns in holding or continuing IBD therapy in the setting of COVID-19 infection, using the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease [SECURE-IBD] registry. METHODS: IBD medications that were stopped due to COVID-19 were recorded in the SECURE-IBD registry in addition to demographic and clinical data. We conducted descriptive analyses to understand characteristics associated with stopping IBD medications in response to active COVID-19 infection. RESULTS: Of 1499 patients, IBD medications were stopped in 518 [34.6%] patients. On bivariate and multivariable analyses, a diagnosis of ulcerative colitis or IBD-unspecified was associated with a lower odds of stopping medication compared with Crohn's disease (adjusted odds ratio [aOR] 0.6, 95% confidence interval [CI] 0.48, 0.75). When evaluating specific medications, 5-aminosalicylic acid was more likely to be continued [p <0.001] whereas anti-tumour necrosis factor therapy and immunomodulator therapy were more likely to be stopped [global p <0.001]. Other demographic and clinical characteristics did not affect prescription patterns. CONCLUSIONS: IBD medications other than immunomodulators were continued in the majority of IBD patients with COVID-19, in the international SECURE-IBD registry. Future studies are needed to understand the impact of stopping or continuing IBD medications on IBD- and COVID-19 related outcomes.

Effect of IBD medications on COVID-19 outcomes: results from an international registry.

OBJECTIVE: We sought to evaluate COVID-19 clinical course in patients with IBD treated with different medication classes and combinations. DESIGN: Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of IBD patients with confirmed COVID-19. We used multivariable regression with a generalised estimating equation accounting for country as a random effect to analyse the association of different medication classes with severe COVID-19, defined as intensive care unit admission, ventilator use and/or death. RESULTS: 1439 cases from 47 countries were included (mean age 44.1 years, 51.4% men) of whom 112 patients (7.8%) had severe COVID-19. Compared with tumour necrosis factor (TNF) antagonist monotherapy, thiopurine monotherapy (adjusted OR (aOR) 4.08, 95% CI 1.73 to 9.61) and combination therapy with TNF antagonist and thiopurine (aOR 4.01, 95% CI 1.65 to 9.78) were associated with an increased risk of severe COVID-19. Any mesalamine/sulfasalazine compared with no mesalamine/sulfasalazine use was associated with an increased risk (aOR 1.70, 95% CI 1.26 to 2.29). This risk estimate increased when using TNF antagonist monotherapy as a reference group (aOR 3.52, 95% CI 1.93 to 6.45). Interleukin-12/23 and integrin antagonists were not associated with significantly different risk than TNF antagonist monotherapy (aOR 0.98, 95% CI 0.12 to 8.06 and aOR 2.42, 95% CI 0.59 to 9.96, respectively). CONCLUSION: Combination therapy and thiopurines may be associated with an increased risk of severe COVID-19. No significant differences were observed when comparing classes of biologicals. These findings warrant confirmation in large population-based cohorts.MKH should be changed to MDK for co-last author line.

Review of the epidemiology and burden of ulcerative colitis in Latin America.

The incidence and prevalence of ulcerative colitis (UC) has been reported to be rising in newly industrialised regions, such as Latin America. Here, we review data from published studies reporting demographics and clinical aspects of UC in Latin America to further understand epidemiology and disease burden. The incidence and prevalence of UC in Latin America varied between regions and studies, ranging between 0.04 to 8.00/100,000 and 0.23 to 76.1/100,000, respectively, and generally increased over the period from 1986 to 2015. The majority of patients with UC were female (53.6-72.6%) and urban residents (77.8-97.4%). Extraintestinal manifestations were reported in approximately 26-89.4% of patients. Use of biologic therapies was generally low (0.8-16.2%), with the exception of Mato Grosso do Sul, Brazil, with a greater proportion of patients tending to receive 5-aminosalicylates, immunosuppressants or corticosteroids; colectomy rates varied between studies (1.5-22%). A high proportion of patients had moderate to severe UC (45.9-73.0%) and, in 11 of 19 studies, the greatest proportion of patients had extensive disease (pancolitis). Colorectal cancer (0-1.7%) and mortality rates (0-7.6%) were low. This evaluation of published studies may influence therapeutic approaches and the development of strategies to improve healthcare access and patient outcomes, although further high-quality studies are required in patients with UC in Latin America.

Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry.

BACKGROUND AND AIMS: The impact of Coronavirus disease 2019 (COVID-19) on patients with inflammatory bowel disease (IBD) is unknown. We sought to characterize the clinical course of COVID-19 among patients with IBD and evaluate the association among demographics, clinical characteristics, and immunosuppressant treatments on COVID-19 outcomes. METHODS: Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of patients with IBD with confirmed COVID-19. We calculated age-standardized mortality ratios and used multivariable logistic regression to identify factors associated with severe COVID-19, defined as intensive care unit admission, ventilator use, and/or death. RESULTS: 525 cases from 33 countries were reported (median age 43 years, 53% men). Thirty-seven patients (7%) had severe COVID-19, 161 (31%) were hospitalized, and 16 patients died (3% case fatality rate). Standardized mortality ratios for patients with IBD were 1.8 (95% confidence interval [CI], 0.9-2.6), 1.5 (95% CI, 0.7-2.2), and 1.7 (95% CI, 0.9-2.5) relative to data from China, Italy, and the United States, respectively. Risk factors for severe COVID-19 among patients with IBD included increasing age (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.02), ≥2 comorbidities (aOR, 2.9; 95% CI, 1.1-7.8), systemic corticosteroids (aOR, 6.9; 95% CI, 2.3-20.5), and sulfasalazine or 5-aminosalicylate use (aOR, 3.1; 95% CI, 1.3-7.7). Tumor necrosis factor antagonist treatment was not associated with severe COVID-19 (aOR, 0.9; 95% CI, 0.4-2.2). CONCLUSIONS: Increasing age, comorbidities, and corticosteroids are associated with severe COVID-19 among patients with IBD, although a causal relationship cannot be definitively established. Notably, tumor necrosis factor antagonists do not appear to be associated with severe COVID-19.

Oral administration of exogenous lactase in tablets for patients diagnosed with lactose intolerance due to primary hypolactasia / Administração oral de lactase exógena em comprimidos em pacientes portadores de intolerância à lactose devido à hipolactasia primária

ABSTRACT Background Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. , Objective Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Methods Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Results Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. Conclusion The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

RESUMO Contexto A hipolactasia primária é uma condição muito frequente na qual há redução da atividade da lactase na mucosa intestinal.A presença de sintomas abdominais devidos à má absorção da lactose presente em alguns casos caracteriza a intolerância à lactose. Objetivo Avaliar a eficácia de um produto contendo lactase exógena em comprimidos comparativamente a de um produto comparador com eficácia comprovada em pacientes portadores de intolerância à lactose. Métodos Estudo multicêntrico, randomizado, de grupos paralelos, com investigador cego, comparativo de não-inferioridade. Cento e vinte e nove (129) pacientes adultos portadores de intolerância à lactose e teste do hidrogênio no ar expirado compatível com o diagnóstico de hipolactasia foram randomizados para receber o produto experimental (Perlatte(r) - Eurofarma Laboratórios S.A.) ou o produto comparador (Lactaid(r) - McNeil Nutritionals, EUA), por via oral (um comprimido, três vezes ao dia), durante 42 dias consecutivos. Resultados Os dados dos 128 pacientes que efetivamente receberam o tratamento do estudo foram avaliados (66 tratados com o produto experimental e 62 com o produto comparador). Os dois grupos se mostraram homogêneos quanto aos dados demográficos e clínicos basais. A média da concentração do hidrogênio expirado aos 90 minutos no teste realizado ao final do tratamento (Dia 42) foi significativamente menor no grupo tratado com o produto experimental (17±18 ppm versus 34±47 ppm na população por protocolo). A diferença entre as médias dos dois grupos foi de -17 ppm (intervalo de confiança de 95% [IC95%]: -31,03; -3,17). O limite superior do IC95% não ultrapassou a margem de não-inferioridade estipulada a priori (7,5 ppm). As análises secundárias de eficácia confirmaram a semelhança entre os tratamentos (populações por protocolo e com intenção de tratamento). A tolerabilidade foi excelente em ambos os grupos e não houve relato de eventos adversos graves relacionados ao produto. Conclusão O produto experimental se mostrou não-inferior ao produto comparador, indicando sua eficácia no tratamento substitutivo da lactase endógena em pacientes portadores de intolerância à lactose.

Anti-Tumor Necrosis Factor α-Related Psoriatic Lesions in Children with Inflammatory Bowel Disease: Case Report and Systematic Literature Review.

We report a child with Crohn's disease and infliximab-induced guttate psoriasis. We also performed a systematic literature review on this intriguing paradoxical phenomenon in children with inflammatory bowel disease.

Optic Neuritis Associated or Not with TNF Antagonists in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Acute optic neuritis [ON] is an inflammatory condition affecting the optic nerve. Clinicians should suspect optic neuritis in cases of painful and rapidly progressive loss of central visual field. This condition may be associated with a multitude of diseases, and mostly with multiple sclerosis [MS] where it may present as an initial symptom. The literature reports that optic neuritis and MS occur in patients with inflammatory bowel disease [IBD] before and after the era of anti-tumour necrosis factor-α [TNFα] drugs. At the present moment, there is little consensus for managing this complication, currently treated with corticosteroids and discontinuation of the causative agents. METHODS: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. We also performed a comprehensive retrospective search of the available literature on this topic. RESULTS: We report herein 12 new cases of ON, including 10 under anti-TNF therapy, collected through the CONFER project. We also compare characteristics of ON associated or not with anti-TNFα agents. CONCLUSIONS: The exceptional and current observation of distant family history of MS in 17% of our patients who developed ON, despite the small number and the lack of a control arm, might be an important signal that should be taken into account in our therapeutic strategies in the future.

Cerebrovascular events in inflammatory bowel disease patients treated with anti-tumour necrosis factor alpha agents.

BACKGROUND AND AIMS: Cerebrovascular accidents [CVA] have rarely been reported in inflammatory bowel disease [IBD] patients treated with anti-tumour necrosis alpha [anti-TNF alpha] agents. Our aim here was to describe the clinical course of CVA in these patients. METHODS: This was a European Crohn's and Colitis Organisation [ECCO] retrospective observational study, performed as part of the CONFER [COllaborative Network For Exceptionally Rare case reports] project. A call to all ECCO members was made to report on IBD patients afflicted with CVA during treatment with anti-TNF alpha agents. Clinical data were recorded in a standardised case report form and analysed for event association with anti-TNF alpha treatment. RESULTS: A total of 19 patients were identified from 16 centres: 14 had Crohn's disease, four ulcerative colitis and one IBD colitis unclassified [median age at diagnosis: 38.0 years, range: 18.6-62.5]. Patients received anti-TNF alpha for a median duration of 11.8 months [range: 0-62] at CVA onset; seven had previously been treated with at least one other anti-TNF alpha agent. Complete neurological recovery was observed in 16 patients. Anti-TNF alpha was discontinued in 16/19 patients. However, recurrent CVA or neurological deterioration was not observed in any of the 11 patients who received anti-TNF alpha after CVA [eight resumed after temporary cessation, three continued without interruption] for a median follow-up of 39.8 months [range: 5.6-98.2]. CONCLUSION: These preliminary findings do not unequivocally indicate a causal role of anti-TNF alpha in CVA complicating IBD. Resuming or continuing anti-TNF alpha in IBD patients with CVA may be feasible and safe in selected cases, but careful weighing of IBD activity versus neurological status is prudent.

Optimising monitoring in the management of Crohn's disease: a physician's perspective.

Management of Crohn's disease has traditionally placed high value on subjective symptom assessment; however, it is increasingly appreciated that patient symptoms and objective parameters of inflammation can be disconnected. Therefore, strategies that objectively monitor inflammatory activity should be utilised throughout the disease course to optimise patient management. Initially, a thorough assessment of the severity, location and extent of disease is needed to ensure a correct diagnosis, identify any complications, help assess prognosis and select appropriate therapy. During follow-up, clinical decision-making should be driven by disease activity monitoring, with the aim of optimising treatment for tight disease control. However, few data exist to guide the choice of monitoring tools and the frequency of their use. Furthermore, adaption of monitoring strategies for symptomatic, asymptomatic and post-operative patients has not been well defined. The Annual excHangE on the ADvances in Inflammatory Bowel Disease (IBD Ahead) 2011 educational programme, which included approximately 600 gastroenterologists from 36 countries, has developed practice recommendations for the optimal monitoring of Crohn's disease based on evidence and/or expert opinion. These recommendations address the need to incorporate different modalities of disease assessment (symptom and endoscopic assessment, measurement of biomarkers of inflammatory activity and cross-sectional imaging) into robust monitoring. Furthermore, the importance of measuring and recording parameters in a standardised fashion to enable longitudinal evaluation of disease activity is highlighted.

Induction or exacerbation of psoriatic lesions during anti-TNF-α therapy for inflammatory bowel disease: a systematic literature review based on 222 cases.

BACKGROUND: Paradoxical cases of psoriatic lesions induced or exacerbated by anti-tumor necrosis factor (TNF)-α therapy have been reported more frequently in recent years, but data related to inflammatory bowel disease (IBD) are rare. A systematic literature review was performed to provide information about this adverse effect in patients with IBD who receive anti-TNF therapy. METHODS: Published studies were identified by a search of Medline, Embase, Cochrane, SciELO, and LILACS databases. RESULTS: A total of 47 studies (222 patients) fulfilled the inclusion criteria and were selected for analysis. Clinical and therapeutic aspects varied considerably among these reports. Of the 222 patients, 78.38% were diagnosed with Crohn's disease, and 48.20% were female. The mean patient age was 26.50 years, and 70.72% of patients had no history of psoriasis. Patients developed psoriasiform lesions (55.86%) more often than other types of psoriatic lesions, and infliximab was the anti-TNF-α therapy that caused the cutaneous reaction in most patients (69.37%). Complete remission of cutaneous lesions was observed in 63.96% of the cases. CONCLUSIONS: We found that psoriatic lesions occurred predominantly in adult patients with Crohn's disease who received infliximab and had no previous history of psoriasis. Most patients can be managed conservatively without discontinuing anti-TNF-α therapy.

Development of the Paris definition of early Crohn's disease for disease-modification trials: results of an international expert opinion process.

We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen experts on inflammatory bowel diseases held an international expert opinion meeting to discuss and agree on a definition for early CD to be used in disease-modification trials. The process included literature searches for the relevant basic-science and clinical evidence. A published preliminary definition of early CD was used as the basis for development of a proposed definition that was discussed at the expert opinion meeting. The participants then derived a final definition, based on best current knowledge, that it is hoped will be of practical use in disease-modification trials in CD.