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Purpose: Inflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time. Methods: This was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children's Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts. Results: A total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18–36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery. Conclusion: Despite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD. [ABSTRACT FROM AUTHOR]

Background: ABP501 is a biosimilar to Reference Adalimumab (HUMIRA®) produced by AMGEN. Adalimumab (ADA) has a marketing authorization for Crohn's disease, ulcerative colitis and other inflammatory or autoimmune diseases. The aim of this study was to evaluate the LISA-TRACKER assays developed by Theradiag (France), for the monitoring of ABP501 and anti-ABP501 antibodies in human serum. Results: 68 ABP501 clinical samples were measured with the LISA TRACKER Duo Adalimumab assay. LISA TRACKER has been validated as suitable for quantification of ABP501 in human serum samples. Accuracy of the LISA-TRACKER was measured using 3 human serum matrices spiked with known levels of biosimilar, 3 levels spanning the dynamic range. Percentages of recovery were ranged from 90 to 120% for biosimilar batch1, and between 93 and 105% for biosimilar batch2. The acceptance criteria (CV < 20%) were met for intra-run (from 3.8 to 16.5%) and inter-run imprecision (from 4.4 to 13.9%) including the two batches. All results were comprised within ± 20% from results, obtained with the kit and sample unexposed in order to evaluate stability of the sample, stability of the kit and consistency of the results. In any case, but two, all percentages of inhibition were > 50% for specificity. Specificity was tested with Biosimilar spiked samples, Biosimilar with Humira® spiked samples, and clinical samples from patients treated with adalimumab biosimilar. All of these samples were spiked with polyclonal antibodies directed against Humira®. Specificity inhibition and specificity detection steps were also part of the validation parameters. Reagents made with ABP501 gave similar results than reagents made with Humira® meeting acceptance criteria. Conclusions: LISA-TRACKER ADA and anti-ADA assays are reliable for the monitoring of patients treated with ABP501. [ABSTRACT FROM AUTHOR]

Half of Crohn's disease patients develop stenosis around 20 years after the disease onset. For a long time, surgery has been the only therapeutic approach for strictures. The introduction of anti-TNFα could be revolutionary in the management of these patients due to their potential role in stenoses' treatment. The aim of our work was to summarize efficacy data of anti-TNFα drugs in stricturing CD patients. Several case series and observational studies have shown that infliximab and adalimumab are effective in determining improvement and remission of stenosis in CD patients in both clinical trials and clinical practice. The injection of intralesional infliximab could be a valid alternative in patients not responding to systemic therapy. Despite the promising literature data, the low level of evidence and the heterogeneity of the available studies do not allow to draw definitive conclusions on the use of TNFα inhibitors for the treatment of strictures. Further prospective randomized studies are needed to confirm and validate this therapeutic approach. [ABSTRACT FROM AUTHOR]

Abstract Background The role of single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease (IBD) is gaining interest. With the advent of novel therapies, personalized treatment in IBD is a future goal. We wondered whether IBD-associated SNPs are able to predict response to anti-TNFα treatment. Methods Data on treatment use and primary response, loss of response and side effects to anti-TNFα treatments were retrieved for 570 IBD patients. rs13361189 (IRGM), rs10210302 (ATG16L1), rs2066844, rs2066845, rs2066847 (NOD2), rs35873774 (XBP1), rs11175593 (LRRK2), rs11465804 (IL23R), rs2301436 (CCR6), rs744166 (STAT3) and rs4821544 (NCF4) SNP status were determined. Results No associations were found between genetic variants of the LRRK2, CCR6, IL23R and NCF4 genes and response to anti-TNFα. For NOD2 and XBP1 associations were found, however, these associations were not strong enough to survive multiple testing corrections. Strikingly, patients carrying the ATG16L1 T300A variant were more likely to be treated with adalimumab, even after correction for disease phenotype, disease behavior and age (p = 0.004, OR 2.8, CI 1.6–5.0). Conclusions Genetic polymorphisms in the known IBD-associated gene ATG16L1 correlate with requirement of treatment, suggesting a different IBD disease phenotype in these patients. Further investigation will need to elucidate the implications of these findings and identify the underlying disease characteristics.

Background and Aim The effects of vedolizumab [VEDO] exposure on perioperative outcomes following surgery for inflammatory bowel disease [IBD] remain controversial. The aim of our study was to compare postoperative morbidity of IBD surgery following treatment with VEDO vs other biologics or no biologics. Methods An institutional review board-approved, prospectively collected database was queried to identify all patients undergoing abdominal surgery for IBD between August 2012 and May 2017. The impact of VEDO within 12 weeks preoperatively on postoperative morbidity was initially assessed with univariate and multivariable analyses on all patients. A case-matched analysis was then carried out comparing patients exposed to VEDO vs other biologic agents, based on gender, age ± 5 years, diagnosis, date of surgery ± 2 years, and surgical procedure. Results Out of 980 patients, 141 received VEDO. The majority of patients [59%] underwent surgery involving end or diverting ostomy creation. The initial multivariate analysis conducted on all patients indicated that VEDO use was independently associated with increased overall morbidity [ p <0.001], but not infectious morbidity [ p = 0.30]. However, the case-matched comparison of 95 VEDO-treated patients vs 95 patients treated with adalimumab or infliximab did not indicate any difference in overall morbidity [ p = 0.32], infectious complications [ p = 0.15], or surgical site infections [ p = 0.12]. Conclusions In a study population having a high rate of surgery involving ostomy creation, the exposure to preoperative VEDO was not associated with an increased morbidity rate when compared with other biologics. [ABSTRACT FROM AUTHOR]

Despite the high rate of postoperative recurrence (POR) in Crohn's disease (CD), there is no widely accepted consensus on its prevention. To compare the efficacy of biological and conventional therapies in preventing POR of CD. We searched four electronic databases up to April 2019 for articles that examined the efficacy of different preventive therapies against POR. Our PICO was: (P) adults with CD who underwent intestinal resection, (I) biological agents, (C) conventional therapies or a placebo, and (O) clinical, endoscopic, and histological POR. Anti-TNFα agents were significantly better in preventing clinical, endoscopic, severe endoscopic and histological POR compared to conventional therapies (OR: 0.508, 95% CI: 0.309–0.834, P = 0.007; OR: 0.312, 95% CI: 0.199–0.380, P < 0.001; OR: 0.195, 95% CI: 0.107–0.356, P < 0.001; and OR: 0.255, 95% CI: 0.106–0.611, P = 0.002, respectively), as well as in the subgroup of nonselected CD patients (OR: 0.324, 95% CI: 0.158–0.664, P = 0.002; OR: 0.225, 95% CI: 0.124–0.409, P < 0.001; and OR: 0.248, 95% CI: 0.070–0.877, P = 0.031, respectively). Infliximab and adalimumab proved to be equally effective in preventing endoscopic POR. Anti-TNFα agents are more effective in preventing clinical, endoscopic and histological POR than conventional therapies, even in nonselected CD patients. [ABSTRACT FROM AUTHOR]

The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars. [ABSTRACT FROM AUTHOR]

Résumé La maladie de Crohn fait partie des maladies inflammatoires chroniques intestinales. D'origine méconnue et multifactorielle, elle atteint différentes parties du tube digestif et se caractérise par des phases de poussées et de rémissions. Un arsenal thérapeutique conséquent permet, en général, d'améliorer le confort de vie. Summary Crohn's disease is a chronic inflammatory condition of the digestive system. Of unknown and multifactorial origin, it affects different parts of the digestive tract and is characterised by phases of flare-ups and remission. There are a significant number of treatments available to improve the patient's quality of life. [ABSTRACT FROM AUTHOR]

Cutaneous adverse events are frequent among patients with inflammatory bowel disease (IBD) treated by anti-Tumor Necrosis Factor (TNF)-α agents, concerning 20% of patients. Infections represent half of skin complications, immune-mediated lesions 40% and, neoplastic lesions and local reactions the remaining percentage. Infections that are mostly caused by bacteria or herpes virus reactivation can usually be treated without anti-TNFa withdrawal. Psoriasis and eczema lesions have typical locations, with a palmo-plantar involvement, folds and scalp eruptions. They could be treated in most of cases with topical steroids and vitamin D. Few patients have to stop anti-TNFα and switch to drug with another mode of action. Dermatologic surveillance is now yearly recommended in IBD patients. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease is associated with an increased likelihood of developing lymphoma. However, it is still controversial if this risk may be attributed to the disease itself or rather represents an effect of immunosuppressive treatment. Although tumor necrosis factor alpha (TNFα) is a key cytokine for cancer immunosurveillance, the potential relationship between anti-TNFα agents and the pathogenesis of lymphoproliferative disorders remains unclear. Here, we describe the case of a patient with severe perianal Crohn’s disease, treated with infliximab monotherapy, whose unusual presentation with acute groin pain required surgical intervention and led to the diagnosis of diffuse large B-cell lymphoma. However, 10 months after this episode, treatment with infliximab was restarted because the patient continued with refractory and disabling perianal disease. Currently, with a follow-up of 36 months, under infliximab 10 mg/kg every 4 weeks, he maintains mild perianal Crohn’s disease and persists in sustained clinical and imaging remission of the lymphoproliferative disorder. [ABSTRACT FROM AUTHOR]

Background: The role of single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease (IBD) is gaining interest. With the advent of novel therapies, personalized treatment in IBD is a future goal. We wondered whether IBD-associated SNPs are able to predict response to anti-TNFα treatment.Methods: Data on treatment use and primary response, loss of response and side effects to anti-TNFα treatments were retrieved for 570 IBD patients. rs13361189 (IRGM), rs10210302 (ATG16L1), rs2066844, rs2066845, rs2066847 (NOD2), rs35873774 (XBP1), rs11175593 (LRRK2), rs11465804 (IL23R), rs2301436 (CCR6), rs744166 (STAT3) and rs4821544 (NCF4) SNP status were determined.Results: No associations were found between genetic variants of the LRRK2, CCR6, IL23R and NCF4 genes and response to anti-TNFα. For NOD2 and XBP1 associations were found, however, these associations were not strong enough to survive multiple testing corrections. Strikingly, patients carrying the ATG16L1 T300A variant were more likely to be treated with adalimumab, even after correction for disease phenotype, disease behavior and age (p = 0.004, OR 2.8, CI 1.6-5.0).Conclusions: Genetic polymorphisms in the known IBD-associated gene ATG16L1 correlate with requirement of treatment, suggesting a different IBD disease phenotype in these patients. Further investigation will need to elucidate the implications of these findings and identify the underlying disease characteristics. [ABSTRACT FROM AUTHOR]

Introduction: Crohn’s disease is an inflammatory bowel disease that has been debated to be associated with bacterial triggers such as Mycobacterium avium subspecies paratuberculosis (MAP). Standard treatment of Crohn’s disease (CD) patients includes a family of immunomodulators and biologics such as Anti-Tumor Necrosis Factor alpha (Anti-TNFα). This cytokine in particular has been known to play vital roles in fighting microbial infections through formation and maintenance of granulomas. Areas covered: This perspective is focused on elucidating the negative effects of using Anti-TNFα therapeutic agents as a treatment option in CD patients who are more likely suspected to have MAP infection, and the role of other immunomodulators in MAP infection. Expert commentary: While treatment with Anti-TNFα is beneficial to reduce inflammation and to provide short term relief to the patients, it also compromises the immune system causing susceptibility to microbial infection. More than 50% of CD patients have shown no response to Anti-TNFα treatment which indicates a demand for introducing novel CD treatment in combination with antibiotics as a future CD treatment plan. [ABSTRACT FROM PUBLISHER]

Background: To review the frequency with which anti-TNF-α loses its effect and dose "intensification" is required for Crohn's disease (CD) treatment.Methods: Electronic databases were searched for eligible studies. Raw data from studies meeting inclusion criteria were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.Results: Eighty-six eligible studies were included. Estimates of loss of response (LOR) incidence ranged from 8 to 71%. The random effects pooled incidence of LOR with a median follow-up of 1-year was 33% (95% CI 29-38, 55 studies, n = 6135). The effect estimate based on data from patients with infliximab was 33% (95% CI 27-40), 30% (95% CI 22-39) for adalimumab, and 41% (95% CI 30-53) for certolizumabpegol. Overall, the mean percentage of patients' LOR to anti-TNFs was 38.5%. The annual risk for LOR was 20.9% per patient-year. The random-effects pooled rate of need for dose intensification with a median follow-up of 1 year was 34% (95% CI 28-41, 38 studies, n = 10,690). The effect estimate for infliximab was 38% (95% CI 28-50), 36% (95% CI 30-43) for adalimumab, and 2% (95% CI 2-3) for certolizumab-pegol. The mean percentage of patients who needed an anti-TNF dose escalation was 23% with an annual risk of 18.5% per patient-year. There was no evidence of publication bias for incidence of LOR but not for the dose intensification (p = 0.001).Conclusions: Overall, around one-third of CD patients experience a LOR and required dose intensification in primary anti-TNF-α responders. [ABSTRACT FROM AUTHOR]

Currently, anti-TNFα antibodies are used to treat Crohn's disease. We report on a 45-year-old Japanese female with Crohn's disease developing SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome following exposure to the anti-TNFα antibody adalimumab. Initially, adalimumab induced remission, but the patient showed SAPHO syndrome 11 weeks following the start of adalimumab therapy for the first time. Cutaneous and articular involvement were exacerbating the condition, so adalimumab was discontinued and the patient was put on low-dose methotrexate to control her symptoms. To our knowledge, this is the first report of SAPHO syndrome occurring during anti-TNF therapy, which is thought to be a paradoxical response to adalimumab. [ABSTRACT FROM AUTHOR]

Background & Aims Therapeutic antibodies against tumor necrosis factor α (anti-TNF) are effective in patients with Crohn's disease (CD). Mucosal healing is a surrogate marker of efficacy, but little is known about the effects of anti-TNF agents on structural damage in the intestine. Small-intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions. A new sonographic quantitative index (the sonographic lesion index for CD [SLIC]) was developed to quantify changes in CD lesions detected by SICUS. We explored whether the SLIC can be used to monitor transmural bowel damage in CD patients during anti-TNF therapy. Methods We performed a prospective study of 29 patients with ileal or ileocolonic CD treated with anti-TNF agents; patients underwent SICUS before and after scheduled induction and maintenance therapy. To determine whether changes that can be detected by SICUS occur independently of anti-TNF therapy, 7 patients with ileal CD treated with mesalamine were enrolled as controls. A clinical response was defined as steroid-free remission, with CD activity index scores less than 150. Results We observed significant improvements in SLIC scores and subscores after induction and maintenance therapy with anti-TNFs, compared with before therapy. SLIC scores and subscores and index classes were improved significantly in patients with vs without clinical responses. Controls had no improvements in terms of CD activity index or SLIC scores, or index classes. Conclusions Sonographic assessment using the quantitative index SLIC can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD. [ABSTRACT FROM AUTHOR]

Résumé Les complications infectieuses pulmonaires, en particulier la tuberculose en contexte d’endémie, furent les premières décrites sous anti-TNFα administrés dans la maladie de Crohn. La pneumopathie interstitielle en est une complication rare, peu connue, souvent grave. Nous rapportons le cas d’un patient de 42 ans, traité par infliximab pour une maladie de Crohn sévère. Il a était hospitalisé deux ans après pour une dyspnée fébrile d’installation sub-aiguë, associée à une toux sèche et des douleurs basithoraciques. L’imagerie objectivait une pneumopathie interstitielle bilatérale. Les prélèvements microbiologiques étaient négatifs. En l’absence de médicament pneumotoxique imputable ou d’autres causes, le diagnostic d’une pneumopathie interstitielle diffuse sous anti-TNFα était évoqué. La mise sous corticothérapie permettait une amélioration spectaculaire. À partir de notre cas, nous soulignons les difficultés diagnostiques et étiologiques devant une pneumopathie interstitielle diffuse au cours d’une maladie de Crohn sous infliximab, les mécanismes physiopathologiques, ainsi que la prise en charge thérapeutique. Les pneumopathies intertstitielles sont des complications qu’il faut évoquer devant l’indication croissante des anti-TNFα dans la maladie de Crohn. Infectious pulmonary complications, in particular in the context of endemic tuberculosis, were first described in patients with Crohn's disease treated with an anti-TNFα drug. Interstitial lung disease (ILD) is a rare, little known, often severe complication. We describe the case of a 42-year-old patient who was being treated with infliximab (an anti-TNFα drug) for severe Crohn's disease. The patient was hospitalized complaining of subacute dyspnea, fever, a dry cough and lower thoracic pain during the previous two years. Imaging showed bilateral interstitial pneumonitis. Microbiological samples were negative. In the absence of treatment with a known pneumotoxic drug or other causes, a diagnosis of diffuse ILD due to the anti- TNFα drug was suggested. Corticotherapy resulted in a spectacular remission. Based on our experience, we discuss the diagnostic and etiologic difficulties encountered in a patient with Crohn's disease who developed ILD while being treated with infliximab and the pathophysiological mechanisms and the therapeutic management in such cases. Interstitial pulmonary complications must be considered before prescribing an anti-TNFα drug for patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

The introduction of biological therapies, particularly anti-TNFα agents, has revolutionized the management of inflammatory bowel disease in those cases which are refractory to conventional treatment; however these drugs are not risk-free and their use has substantially increased the cost of treatment. As marketing protection expires for original, first-generation biopharmaceuticals, lower-cost “copies” of these drugs produced by competitor companies—referred to as biosimilars—are already entering the market. In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients, a decision based largely on efficacy and safety data generated in studies of patients with ankylosing spondylitis and rheumatoid arthritis. For many clinicians, extrapolation practices and the general question of interchangeability between biosimilars and reference biologics are cause for concern. In the present paper, the Italian Group for inflammatory bowel disease presents its statements on these issues, with emphasis on the peculiar clinical characteristics of inflammatory bowel disease and the importance of providing physicians and patients with adequate information and guarantees on the safety and efficacy of these new drugs in the specific setting of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

The treatment of Crohn's disease in children has undergone a revolution in the past decade following studies that have demonstrated the efficacy of anti-TNFα agents in producing durable clinical response/remission as well as reversal of growth delay in many patients. The positioning of biologic therapy continues to be debated. Should it be reserved for children failing conventional therapy including immunomodulators or should it be used as primary therapy shortly after diagnosis in children with more severe disease likely to suffer a more complicated disease course? Risk stratification will be crucial to any therapeutic decisions and emerging data hold promise that identification of those most likely to benefit will be available in the near future. [ABSTRACT FROM AUTHOR]

Abstract: Background: Infliximab (IFX) and adalimumab (ADA) are the key treatments for Crohn's Disease (CD), unresponsive to standard treatments. Our aim was to compare the efficacy and safety of IFX and ADA in treating CD in clinical practice. Methods: One hundred and twenty-six patients (61 M, 65 F, mean age 36.2years, range 19–67years), affected by CD, were treated with infliximab (IFX, 59 patients) or adalimumab (ADA, 66 patients). Clinical efficacy, mucosal healing (MH), histological healing (HH), and safety were assessed. MH was defined complicated if healing of ulcers occurred with deformation of bowel profile and/or complete colonoscopy was impossible because of scars. Results: Patients were followed-up for 36months. No difference was found between IFX and ADA in maintaining long-term clinical remission, MH and HH. Complicated MH was present in 17 (28.8%) patients in IFX group and in 7 (10.6%) patients in ADA group (p=0.012). In 9 (15.2%) patients in IFX group and 2 (3.0%) patients in ADA group colonoscopy was incomplete without cecal intubation or terminal ileum exploration (p=0.024). Side effects were similar in both groups. Conclusions: Both IFX and ADA seem to be effective and safe in long-term outpatient treatment of CD in clinical practice. [Copyright &y& Elsevier]

The pathogenesis of inflammatory bowel disease (IBD) remains incompletely understood, but is thought to be a consequence of immune dysregulation, impaired mucosal integrity, enteric bacterial dysbiosis and genetic susceptibility factors. Recent drug advances in the treatment of IBD have clarified the role of existing medication, including 5-aminosalicylic acids (5-ASAs) and has seen a burgeoning use of treatment with biologicals. With recent advances in our understanding of these debilitating diseases, it is hoped that novel therapeutic targets can be identified. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Active Crohn''s disease affects intestine but may alter other locations as eyes vasculature. Previous studies provide evidence of elevated blood flow velocities (BFv) and volume (BFV) in superior mesenteric artery (SMA). We prospectively studied hemodynamics in feeding arteries of bowel and eyes before and 2weeks after treatment induction with anti-TNFα. Methods: Fifteen patients (5 females, 10 males, 35.4±9.0years, mean±SD) with active Crohn''s disease for 7.5±7.7years were enrolled. Ultrasound imaging was performed before and 2weeks after treatment in SMA and retrobulbar arteries: central retinal (CRA), temporal posterior ciliary (TPCA) and ophthalmic (OA) arteries. Serum markers of inflammation (CRP and fibrinogen), arterial blood pressures (ABP) and skin flow-mediated dilation (sFMD) were measured and patients were compared to 10 control age- and sex-matched subjects. Results: Before treatment, CRP and fibrinogen plasma concentrations, SMA BFV (339±100mL/min) were higher in patients than in controls by 8.5-fold (p<0.001), 1.4-fold (p<0.01) and 1.5-fold, respectively (p<0.01). BFv in CRA (3.5±0.7cm/s) and TPCA (4.4±1.0cm/s), sFMD (371±469%) were significantly lower than in controls by 83%, 73% and 52% respectively (p<0.05). Two weeks after treatment, CRP and fibrinogen decreased, SMA BFV was normalized (230±39L/min, p<0.01), BFv in CRA, TPCA and OA increased respectively to 4.0±1.1 (p<0.05), 5.2±1.4 (p<0.001), 8.9±3cm/s (p<0.05). ABP and sFMD remained unchanged. Conclusions: In active Crohn''s disease, a first anti-TNFα administration rapidly normalized concomitantly plasma inflammatory markers and blood-flows in the mesenteric and retrobulbar arteries without affecting blood pressure and endothelial function. [Copyright &y& Elsevier]

Crohn's disease is a chronic inflammatory bowel disease. It typically presents with symptoms including abdominal pain, bloody diarrhoea, fistulae and stricturing of the bowel, resulting in obstruction. There is no medical cure for the condition; current medical approaches are concerned with symptom reduction and promotion of quality of life. These outcomes can be difficult to achieve, and involve invasive treatments, often with undesirable side-effects for the patient. Traditionally, Crohn's disease has been managed with anti-inflammatory drugs including steroids and aminosalicylates, with the more refractory cases requiring the introduction of immunomodulating drugs such as azathioprine. Despite these approaches, a significant number of patients will continue to experience ongoing and troublesome symptoms, severely impacting on their quality of life, and often resulting in surgery. Adalimumab (Humira) was the second biological agent to be licensed for the treatment of Crohn's disease in late 2007. Like infliximab, it is a monoclonal antibody which binds to anti-tumour necrosis factor α (anti-TNFα). This article will outline the clinical use of adalimumab, and discuss its current place in the therapeutic pathway of patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

An unusually large number of cases of tuberculosis, often with miliary or dissemination, has been reported in patients taking infliximab for rheumatoid arthritis or Crohn’s disease. Recommendations have been issued in France regarding the definition of high-risk patients, the screening methods to be used in these patients, and possible prophylactic treatments. The present update is also intended to help physicians manage tuberculosis occurring before or during infliximab therapy. [Copyright &y& Elsevier]

An unusually large number of cases of tuberculosis, often with miliary or dissemination, has been reported in patients taking infliximab for rheumatoid arthritis or Crohn’s disease. Recommendations have been issued in France regarding the definition of high-risk patients, the screening methods to be used in these patients, and possible prophylactic treatments. The present update is also intended to help physicians manage tuberculosis occurring before or during infliximab therapy. [ABSTRACT FROM AUTHOR]

Summary All practitioners caring for patients with Crohn's disease (CD) must know all the various aspects of anoperineal lesions in this singular entity. Suppuration in CD does not follow the classic routes and spaces of diffusion and is often associated with endolumenal lesions that can evolve on their own. Abscesses and fistulas require specific medico-surgical management where seton drainage, staged operative and sphincter-sparing procedures have a dominant place. The variability of associated lesions and the particularly individualized efficacy of drugs call for case-by-case management, thus, making standardization and comparisons difficult. Recent therapeutic progress has led to modifications of the minimally invasive management policies practiced in the last decades. [ABSTRACT FROM AUTHOR]