Crohn Disease: Travis SP

Carter MJ, Lobo AJ, Travis SP, Anonymous00282. · Division of Molecular and Genetic Medicine, Royal Hallamshire Hospital, Sheffield, UK. · Gut. · Pubmed #15306569 links to  free full text

This publication has no abstract.

Cummings JR, Keshav S, Travis SP. · Gastroenterology Unit, John Radcliffe Hospital, Oxford OX3 9DU. · BMJ. · Pubmed #18467414 No free full text.

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Steinhart AH, Forbes A, Mills EC, Rodgers-Gray BS, Travis SP. · Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. · Aliment Pharmacol Ther. · Pubmed #17539978 No free full text.

Abstract: AIM: To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release mesalazines in maintaining medically and surgically induced Crohn's disease remission. METHODS: A systematic search identified 13 randomized controlled trials (RCTs). The rate of symptomatic relapse (Crohn's disease activity index >150, or an increase in baseline by at least 60-100 points) was extracted from each randomized controlled trial. Pooled odds ratios (OR), the number needed to treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were calculated. RESULTS: Treatment with pH 7-dependent mesalazine significantly reduced the risk of relapse in patients with either surgically [OR 0.28; 95% confidence interval (CI) 0.12-0.65; P = 0.0032] or medically induced remission (OR 0.38; 95% CI 0.17-0.85; P = 0.0113). However, treatment with controlled-release mesalazine and pH 6-dependent mesalazine failed to show any significant advantage over placebo. The NNT to maintain surgically or medically induced remission was lowest for pH 7-dependent mesalazine (NNT = 4 and 5, respectively; NNT = 15 and 16 for controlled-release mesalazine and NNT = 11 and 23 for pH 6-dependent mesalazine). Therapeutic benefit was highest for pH 7-dependent mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9% (surgical) and 6.4% (medical) for controlled-release mesalazine, and 9.8% and 4.4%, respectively, for pH 6-dependent mesalazine. CONCLUSION: Further trials of pH 7-dependent mesalazine formulations are warranted in the maintenance of remission in Crohn's disease.

Ganesan S, Travis SP, Ahmad T, Jazrawi R. · Phase 1 Clinical Trials Unit, 119 Looseleigh Lane, Derriford, Plymouth, PL6 5HH, UK. · Curr Opin Investig Drugs. · Pubmed #12498004 No free full text.

Abstract: Therapeutic options for patients with refractory ulcerative colitis or Crohn's disease have recently been augmented by the introduction of biological therapies. The pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha is present in elevated concentrations in patients with inflammatory bowel disease and inhibitors of TNF alpha have proved effective as treatment. Strategies aimed at reducing TNF in patients with Crohn's disease, include the mouse/human chimeric monoclonal antibody, infliximab (Centocor Inc), the humanized monoclonal antibody, CDP-571 (Celltech Group plc), the human recombinant TNF receptor fusion protein, etanercept (Immunex Corp), and thalidomide. New approaches, including the use of soluble TNF receptors, appear promising. This article reviews the evidence of therapeutic inhibition of TNF.

Ganesan S, Travis SP, Ahmad T, Jazrawi R. · Phase 1 Clinical Trials Unit, 119 Looseleigh Lane, Derriford, Plymouth, PL6 5HH, UK. · Curr Opin Investig Drugs. · Pubmed #12498003 No free full text.

Abstract: Tumor necrosis factor-alpha (TNF alpha) is one of several pro-inflammatory cytokines that have been implicated in the pathogenesis of Crohn's disease (CD). Treatment with antibodies to TNF alpha has been shown to reduce mucosal inflammation in the disease, promote tissue healing, achieve and maintain remission, improve the CD activity index (CDAI) and improve the quality of life. The first part of this article reviews the role of TNF alpha in CD.

Hyder SA, Travis SP, Jewell DP, McC Mortensen NJ, George BD. · Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom. · Dis Colon Rectum. · Pubmed #17041753 No free full text.

Abstract: INTRODUCTION: Infliximab is a monoclonal antibody against tumor necrosis factor-alpha, which has been shown to be effective in fistulating Crohn's disease. The safety of infliximab in patients with potential perianal sepsis is uncertain. This study was designed to assess the safety and outcome of infliximab therapy combined with surgery for patients with fistulating anal Crohn's disease. METHODS: All patients receiving infliximab for fistulating anal Crohn's disease between 2000 and 2004 were studied. Patients' demographics, clinical findings, magnetic resonance imaging, and examination under anesthesia were recorded. Perianal Crohn's disease activity index before and 8 to 12 weeks after three infusions of infliximab (5 mg/kg) were recorded. Routine policy was to insert drainage seton sutures at the time of preinfliximab examination under anesthesia and then remove it after the second infusion. Complications of treatment and outcome at the last clinic follow-up were recorded. RESULTS: Twenty-two patients underwent infliximab treatment (6 males; median age, 35 (range, 16-60) years). Twenty-one patients had preinfliximab examination under anesthesia: 12 required abscess drainage; 17 had at least one drainage seton suture inserted. Fourteen patients underwent pretreatment magnetic resonance imaging to identify clinically occult collections. All but one patient were established on immunomodulator therapy before infliximab treatment. Perianal Crohn's disease activity index improved significantly after infliximab infusion (preinfusion: median, 11, range, 8-17; postinfusion: median, 8, range, 5-16; P<0.001). There were no serious complications of infliximab treatment. At median follow-up of 21 (range, 4-31) months, only four patients achieved sustained fistula healing. Five patients have required defunctioning or proctectomy. Four patients have required repeated infusions of infliximab. CONCLUSIONS: Infliximab therapy in combination with examination under anesthesia/seton drainage is a safe and effective short-term treatment for fistulating anal Crohn's disease. Long-term fistula healing rates are low.

McGovern DP, Butler H, Ahmad T, Paolucci M, van Heel DA, Negoro K, Hysi P, Ragoussis J, Travis SP, Cardon LR, Jewell DP. · Wellcome Trust Centre for Human Genetics, University of Oxford, Drive, Headington, Oxford OX3 7BN, England, UK. · Gastroenterology. · Pubmed #17030188 No free full text.

Abstract: BACKGROUND & AIMS: The identification of the association between Crohn's disease (CD) and NOD2 (CARD15) confirmed both the heritability of CD and highlighted the role of the nuclear factor kappaB (NFkappaB) pathway in disease pathogenesis. Other susceptibility loci exist. TUCAN (CARD8) is located beneath a CD peak of linkage on chromosome 19q. TUCAN is expressed in the gut and is a negative regulator of NFkappaB, making it an excellent candidate gene for gastrointestinal inflammation. METHODS: Ten single nucleotide polymorphisms (SNP) across TUCAN were genotyped in 365 controls, 372 patients with CD, and 373 patients with ulcerative colitis. A diagnostic panel for CD was constructed using smoking status and TUCAN, NOD2, IBD5, NOD1, and TNFSF15 data. RESULTS: We demonstrate significant association between a TUCAN SNP and CD (OR 1.35, P = .0083). The association was more pronounced with disease affecting sites other than the colon (odds ratio, 1.52) and NOD2-negative CD (odds ratio, 1.50). Combination of these data with smoking and NOD2, IBD5, NOD1, and TNFSF15 status demonstrated very strong associations with CD and high sensitivities (96.3%), specificities (99.4%), and likelihood ratios (12.8) for CD, although further work will be needed before this model can be translated into direct clinical utility. CONCLUSIONS: We have shown an association between a likely functional polymorphism in TUCAN and CD. The combination of these data in a genetic panel suggests that clinicians may soon be able to translate genetic advances into direct benefits for patients.

Travis SP, Stange EF, Lémann M, Oresland T, Chowers Y, Forbes A, D'Haens G, Kitis G, Cortot A, Prantera C, Marteau P, Colombel JF, Gionchetti P, Bouhnik Y, Tiret E, Kroesen J, Starlinger M, Mortensen NJ, Anonymous00005. · John Radcliffe Hospital, Oxford OX3 9DU, UK. · Gut. · Pubmed #16481629 links to  free full text

Abstract: This second section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns treatment of active disease, maintenance of medically induced remission, and surgery. The first section on definitions and diagnosis includes the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The third section on special situations in Crohn's disease includes postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy for Crohn's disease.

Stange EF, Travis SP, Vermeire S, Beglinger C, Kupcinkas L, Geboes K, Barakauskiene A, Villanacci V, Von Herbay A, Warren BF, Gasche C, Tilg H, Schreiber SW, Schölmerich J, Reinisch W, Anonymous00004. · John Radcliffe Hospital, Oxford OX3 9DU, UK. · Gut. · Pubmed #16481628 links to  free full text

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Frenz MB, Dunckley P, Camporota L, Jewell DP, Travis SP. · Department of Gastroenterology, John Radcliffe Hospital, Headley Way, Headington, Oxford, United Kingdom. · Am J Gastroenterol. · Pubmed #15842587 No free full text.

Abstract: The Crohn's disease activity index (CDAI) is the most widely used measure of clinical disease activity in patients entered into clinical trials. The prospective nature of the CDAI calculation precludes its use as a clinical assessment tool. We compared the retrospective evaluation of the CDAI with the prospective evaluation in a heterogeneous patient population of 100 patients with Crohn's disease. The correlation between the two assessment methods was good with an r-value of 0.84 (p < 0,0001). There was a tendency of patients with a high retrospective CDAI to have a lower prospective CDAI which is explained by intention to treat. This study shows that a retrospective assisted evaluation of the CDAI is as accurate as the traditional prospective evaluation.

Travis SP. · John Radcliffe Hospital, Oxford OX3 9DU, UK. · Gut. · Pubmed #12235078 links to  free full text

This publication has no abstract.

McGovern DP, Travis SP. · No affiliation provided · Gut. · Pubmed #15951558 links to  free full text

This publication has no abstract.