Ulcerative Colitis: Travis S

Travis S. · Gastroenterology Unit, John Radcliffe Hospital, Oxford OX3 9DU, UK. · Curr Gastroenterol Rep. · Pubmed #16313878 No free full text.

Abstract: Advances (from 2004 to 2006) in the use of conventional agents include the molecular mechanisms of action, which have implications for monitoring (azathioprine and thioguanosine triphosphate) and chemoprevention (mesalamine and peroxisome proliferator activated receptor gamma). Advances in biotherapy include new data on monoclonal antibodies (infliximab in ulcerative colitis, adalimumab, certolizumab pegol, fontolizumab, selective anti-adhesion molecules, and others), antisense oligonucleotides, the development of small molecules, and cell-gene therapy (including helminth ova, leukocytapheresis, stem cell transplantation, and probiotic intestinal mucosal delivery systems). However, management of inflammatory bowel disease is about more than drug therapy, dose, and timing. The goals remain induction of remission, limitation of side effects, modification of the pattern of disease, and avoidance of complications. With the cost and complexity of biotherapy, inflammatory bowel disease is emerging as a specific subspecialty.

Travis S, Yap LM, Hawkey C, Warren B, Lazarov M, Fong T, Tesi RJ, Anonymous00222. · Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. · Inflamm Bowel Dis. · Pubmed #16043985 No free full text.

Abstract: BACKGROUND: RDP58 is a novel anti-inflammatory d-amino acid decapeptide that inhibits synthesis of proinflammatory cytokines by disrupting cell signaling at the pre-MAPK MyD88-IRAK-TRAF6 protein complex. We therefore evaluated its efficacy and safety in parallel multicenter, double-blind, randomized concept studies in ulcerative colitis (UC). METHODS: In the first trial, 34 patients with mild to moderate active UC were randomized (1:2) to placebo (n = 13) or RDP58 100 mg (n = 21). In the second trial, 93 similar patients were randomized (1:1:1) to placebo (n = 30) RDP58 200 mg (n = 31), or RDP 300 mg (n = 32). In both studies, treatment success was defined as a simple clinical colitis activity index score of no more than 3 at 28 days. Sigmoidoscopy and rectal biopsy (at baseline and 28 days) and safety measures (baseline and 28 and 56 days) were other endpoints. RESULTS: Treatment success on RDP 100 mg was 29% versus 46% on placebo (P = 0.46). There were no significant differences in sigmoidoscopy or histology score. In the second study, treatment success on the higher doses of RDP58 (200 and 300 mg) was 71% and 72%, respectively, versus 43% on placebo (P = 0.016). Improvements in sigmoidoscopy scores (41% on 200 mg and 46% on 300 mg versus 32% on placebo) did not reach significance, but histology scores improved significantly (P = 0.002) versus placebo. Overall, adverse events were no different between placebo (3.3 +/- 2.4) and RDP58 (2.7 +/- 1.4, 300-mg group). CONCLUSIONS: RDP58 at a dose of 200 or 300 mg, but not 100 mg, was effective in mild-to-moderate UC. RDP58 was safe and well tolerated, and its novel action makes it an attractive potential therapy.

Bourreille A, Ignjatovic A, Aabakken L, Loftus EV, Eliakim R, Pennazio M, Bouhnik Y, Seidman E, Keuchel M, Albert JG, Ardizzone S, Bar-Meir S, Bisschops R, Despott EJ, Fortun PF, Heuschkel R, Kammermeier J, Leighton JA, Mantzaris GJ, Moussata D, Lo S, Paulsen V, Panés J, Radford-Smith G, Reinisch W, Rondonotti E, Sanders DS, Swoger JM, Yamamoto H, Travis S, Colombel JF, Van Gossum A, Anonymous00249. · Institut des Maladies de l'Appareil Digestif, CHU, Université de Nantes, Nantes, France. · Endoscopy. · Pubmed #19588292 No free full text.

Abstract: Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Goldacre MJ, Duncan M, Cook-Mozaffari P, Griffith M, Travis S. · Unit of Health-Care Epidemiology, Department of Public Health, University of Oxford, John Radcliffe Hospital, Oxford, UK. · Eur J Gastroenterol Hepatol. · Pubmed #18188028 No free full text.

Abstract: BACKGROUND: When gastrointestinal diseases are certified as causes of death, they are often not selected as the underlying cause. Until recently, only one underlying cause of death has been coded and analysed in official national statistics in England and many other countries. AIMS: To report on the total 'burden of mortality' from some common gastrointestinal diseases, and whether it has changed over time, including all certified causes of death as well as underlying causes, (i) in the Oxford region from 1979 to 2003, (ii) in England from 1996 to 2003; and to quantify the under-ascertainment of cause-specific mortality when based on underlying cause alone. METHODS: We searched death certificate data from the Oxford Record Linkage Study database, and from English national data, for specified gastrointestinal diseases certified as underlying or contributory causes of death. RESULTS: For all the conditions studied, underlying-cause-coded mortality missed a substantial percentage of all certified deaths. The extent of underestimation varied according to the periods in which different criteria were used for the selection of the underlying cause. For example, in Oxford, in the latest period 1993-2003, underlying-cause-coded mortality identified only 37% of all death certificates with ulcerative colitis, 47% of Crohn's disease, between 62 and 68% for the different types of peptic ulcer and 66% of diverticular disease. CONCLUSIONS: Studies of mortality for these diseases should take account of all certified causes as well as underlying-cause mortality. This is particularly important for analyses that go across periods of change to the rules for selecting the underlying cause of death.

Travis S. · Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #16327832 No free full text.

This publication has no abstract.

Campbell S, Travis S, Jewell D. · John Radcliffe Hospital, Oxford, UK. · Eur J Gastroenterol Hepatol. · Pubmed #15647646 No free full text.

Abstract: BACKGROUND: Within a lifetime, approximately 15% of ulcerative colitis (UC) patients will have a severe relapse necessitating admission to hospital. Despite intravenous steroid treatment, approximately 25% will require either surgery or ciclosporin (CsA) rescue therapy. Initial response rates to CsA have been encouraging, but remission rates have been disappointing. There is a paucity of long-term data on UC patients who have been brought into remission with CsA. OBJECTIVES: To report our 7 year experience on the use of CsA in acute UC and to highlight long-term follow-up data on these patients. PATIENTS AND METHODS: A retrospective database of 76 UC patients requiring CsA between 1996 and 2003 was constructed. CsA was started on the basis of their C-reactive protein (CRP) and/or stool frequency after 3 days or after 5-7 days of i.v. hydrocortisone. The patients (33 female, 43 male, mean age 44.5 years) were followed up for a median 2.9 years (range 0.2-7.0 years). Fifty-four patients received i.v. CsA (4 mg/kg), while 22 received oral CsA (5 mg/kg). Long-term outcome was evaluated by Kaplan-Meier survival analysis: time to first relapse and time to surgery. RESULTS: Median disease duration was 6.6 years. Median CRP and stool frequency at day 3 was 20 mg/l and 6 per day, respectively. Fifty-six patients (74%) achieved initial remission. CsA was discontinued in only four patients due to side effects. Duration of i.v. steroids or the addition of AZA did not improve time to first relapse or time to surgery. Comparison between i.v. CsA and oral CsA revealed a statistically significant difference in time to first relapse (P < 0.01) and time to surgery (P < 0.05) in favour of oral CsA. CONCLUSIONS: These data describe the long-term outcome of the largest series of patients so far reported that have had treatment with CsA for severe refractory UC. If patients achieved initial remission with CsA, after 1 year, 65% had relapsed and after 3 years 90% had relapsed. After 7 years, 58% had come to colectomy. Minor side effects were frequent, but none were life threatening. There was no increase in post-operative complications in those who came to colectomy.

Travis S. · John Radcliffe Hospital, Oxford, UK. · Eur J Gastroenterol Hepatol. · Pubmed #12610313 No free full text.

Abstract: This review in depth considers the thiopurines azathioprine, 6-mercaptopurine and 6-thioguanine, methotrexate, ciclosporin, infliximab and less well-established immunomodulators (including thalidomide, mycophenolate, tacrolimus and natalizumab among others) in their role of modifying the course of ulcerative colitis and Crohn's disease. The five papers are preceded by an overview on the therapeutic order of precedence, the indications and duration of therapy, as well as future concepts.

Fraser AG, Morton D, McGovern D, Travis S, Jewell DP. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Aliment Pharmacol Ther. · Pubmed #11929386 links to  free full text

Abstract: BACKGROUND: The management of patients with inflammatory bowel disease who are resistant to or intolerant of azathioprine remains a challenge. Low-dose methotrexate has been shown to be effective in inducing remission in Crohn's disease. AIM: This review was conducted because there are limited long-term follow-up data during and after stopping treatment. There are also limited data on the use of methotrexate in ulcerative colitis. METHODS: The study was a retrospective review of clinical notes. Remission was defined as minimal bowel symptoms without the need for oral steroids for 3 months. Relapse was defined as bowel symptoms that required steroid treatment or surgery. RESULTS: Seventy patients were reviewed; 48 had Crohn's disease and 22 had ulcerative colitis. The mean duration of treatment was 17.1 months; the mean maintenance dose was 20 mg weekly. Remission was achieved in 34 of 55 patients who completed more than 3 months of treatment (62%). Life-table analysis showed that the chances of remaining in remission at 12, 24 and 36 months (if treatment was continued) were 90%, 73% and 51%, respectively. The chances of remaining in remission after stopping treatment at 6, 12 and 18 months were 42%, 21% and 16%, respectively. The dose of methotrexate (mg/kg) was associated with the induction of remission (P=0.02). Treatment was equally effective for Crohn's disease and ulcerative colitis. CONCLUSIONS: Maintenance methotrexate treatment gives acceptable remission rates for treatment periods up to 3 years. After stopping treatment, relapse is frequent and occurs early (usually within 1 year).