Maintenance Therapy in Crohn's Disease

Symptoms of active Crohn’s disease may respond to one or more of a number of classes of drug therapies. These include systemic glucocorticoids, budesonide, sulphasalazine, mesalazine (5-aminosalicylates), immunosuppressive agents and antibiotics. More recently, a chimeric mouse-human antibody to tumour necrosis factor (infliximab) has been shown to induce clinical remission and endoscopic improvement in patients with moderately active Crohn’s disease refractory to other therapies. Despite this wide range of existing therapies and the potential of emerging biological therapies, recurrent Crohn’s disease continues to be a major impediment to the fulfilment of a normal lifestyle and optimal quality of life for patients with Crohn’s disease. Many drugs known to be effective for the treatment of active disease have been tried as maintenance therapy to prevent disease relapse or recurrence following medical or surgical therapy. The available evidence suggests that most of these drugs are not as useful in maintaining remission as they are in inducing it. Systemic glucocorticoids, budesonide, mesalazine (5-aminosalicylates), sulphasalazine and antibiotics are all associated with either marginal therapeutic gain in the setting of maintenance therapy or unacceptable long term toxicity. The immunosuppressive agents azathioprine, 6-mercaptopurine and methotrexate have been shown to have a beneficial effect in maintaining remission and may be helpful as steroid-sparing agents. Repeated infusions of antitumour necrosis factor antibody maintain the improvements observed after one or two initial infusions. The relative long term safety, efficacy and cost effectiveness of the various choices of maintenance therapy remain to be determined

Combination Ciprofloxacin and Metronidazole for Active Crohn’s Disease

Recent experimental evidence underscores the contribution of intestinal bacteria to the inflammatory process of Crohn's disease. This open study examined the efficacy and safety of combination ciprofloxacin and metronidazole for patients with active Crohn's disease of the ileum and/or colon. Seventy-two patients with active Crohn's disease of the ileum (n=27), ileocolon (n=22) or colon (n=23) were treated with ciprofloxacin 500 mg bid and metronidazole 250 mg tid for a mean of 10 weeks. Clinical remission was defined as a Harvey-Bradshaw index of three points or less; an index reduction of at least three points indicated a clinical response. Clinical remission was observed in 49 patients (68%), and 55 patients (76%) showed a clinical response. A clinical response was noted in 29 of 43 patients (67%) who were not taking concurrent prednisone treatment and in 26 of 29 patients (90%) receiving prednisone (mean dose of 15 mg/day). A clinical response also occurred in a greater proportion of patients with colonic disease, with or without ileal involvement (84%), compared with patients with ileal disease alone (64%), and in patients without resection (86%) compared with those with previous resection (61%). Five patients discontinued antibiotics because of adverse events. After a mean follow-up of nine months, clinical remission was maintained in 26 patients off treatment and in 12 patients who continued antibiotic therapy. Ciprofloxacin in combination with metronidazole is well tolerated and appears to play a beneficial role in achieving clinical remission for patients with active Crohn's disease, particularly when there is involvement of the colon

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29)

Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work

Clinical Perspectives - Biologics in IBD: What's All the Fuss?

Up until the present time, agents with relatively nonspecific anti-inflammatory or immunomodulatory effects such as 5-acetylsalicylic acid, corticosteroids and azathioprine have been the mainstay of inflammatory bowel disease medical therapy. These drugs have been quite useful in one or more clinical settings, but they have been hampered by modest efficacy, significant toxicity or both. With greater understanding of the specific pathways of the gut mucosal immune response, it is hoped that newer biologic response modifiers will provide better efficacy, with an improved adverse event profile compared with older existing therapies. This article examines the evidence behind the use of biologic therapies such as anti-tumour necrosis factor-alpha, interleukin-10, interleukin-11, anti-integrin antibody and antisense intercellular adhesion molecule-1 oligonucleotide

IBD 2009: Emerging Research Frontiers on the Path to a Cure

The Crohn’s and Colitis Foundation of Canada (CCFC) hosted a research symposium in April 2009. The current article presents short synopses of the presentations given at that symposium. Invitees included CCFC-funded clinician-scientists and researchers, research administrators and international leaders in inflammatory bowel disease research. Research challenges were outlined while acknowledging advances made in several domains relevant to informing the search for cures. Following the scientific presentations, discussions endorsed current activities of the CCFC and supported the creation of a new pediatric inflammatory bowel disease initiative

Antibiotic Therapy for Crohn’s Disease: A Review

Increasing evidence suggests that gut bacteria play a pathogenic role in Crohn’s disease (CD), providing a rationale for the use of antibiotics in the primary treatment of the disease. While there are data to suggest that antibiotics may be effective in treating active luminal, particularly colonic, and/or perianal CD, evidence for their use in these settings is hampered by the lack of well-designed, adequately powered, placebo-controlled trials. Furthermore, although nitroimidazole antibiotics have been shown to reduce postoperative recurrence following ileocolonic resection, their use is limited by side effects. There is a current need for rigorous multicentre studies looking into the role of antibiotics in treating perianal and luminal CD, as well as a need for the large-scale assessment of novel antibiotics, with low systemic absorption, which may improve patient tolerance

Clinical Practice Guidelines for the Medical Management of Nonhospitalized Ulcerative Colitis: The Patient Perspective

A series of clinical practice guidelines were recently developed by the Canadian Association of Gastroenterology (CAG) to provide clinicians with recommendations for the medical management of nonhospitalized ulcerative colitis (UC) patients. These guidelines were developed, reviewed and agreed on by expert clinicians and methodologists. Following the finalization of the guidelines, a group of patients with UC as well as several inflammatory bowel disease clinicians, were brought together for a half-day workshop to provide feedback from the patient perspective. At the workshop, the guideline development process was described and the guidelines were reviewed to ensure comprehension. Patients then had the opportunity to provide their insight to the relevance of the guideline development process and the content of the guidelines as it related to their personal experiences with UC. The patient group believed that, although the new guidelines will be a tremendous resource for the health care provider community, a more ‘lay-friendly’ version would better facilitate dialogue between patients and their health care practitioners. The importance of the patient/physician relationship is paramount when making decisions regarding treatment plans, in which patient preferences play a key role in determining the most appropriate therapy and dosing regimen, which, in turn, impact the likelihood of adherence to the treatment plan. It was also believed that quality of life issues were not fully addressed in the guidelines. Much could be learned from shared experiences and coping strategies that would empower patients to take charge of their health and become equal partners with their care providers