Ulcerative Colitis: Feagan B

Baumgart DC, Macdonald JK, Feagan B. · Department of Medicine, Division of Gastroenterology & Hepatology , Charité Medical Center, Virchow Hospital , Medical School of the Humboldt-University, Augustenburger Platz 1, Berlin, Germany, 13353. · Cochrane Database Syst Rev. · Pubmed #18646177 No free full text.

Abstract: BACKGROUND: There are a limited number of treatment options for patients with refractory ulcerative colitis. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that tacrolimus may be effective treatment for ulcerative colitis. OBJECTIVES: This review aims to evaluate the efficacy of tacrolimus for induction of remission in patients with corticosteroid refractory ulcerative colitis. SEARCH STRATEGY: MEDLINE (PubMed), The Cochrane Central Register of Controlled Trials, the IBD/FBD review group specialized register and the ISI-Research Institute were searched (January 1997 to November 2007) to identify relevant studies all randomized trials. SELECTION CRITERIA: Each author independently reviewed potentially relevant studies to determine eligibility based on the pre-specified criteria. DATA COLLECTION AND ANALYSIS: A data extraction form was developed and used to extract data from included studies. Two authors independently extracted data. Data were analyzed using Review Manager (RevMan 4.2.9). The primary outcomes were induction of remission and clinical improvement, as defined by the studies and expressed as a percentage of the patients randomized (intention to treat analysis). MAIN RESULTS: One randomized controlled trial comparing high target serum concentration and low target serum concentration tacrolimus versus placebo was identified and included in the review. Clinical remission was observed in 19% (4/21) of patients in the high target serum concentration group, in 9% (2/22) in the low target serum concentration group and in 5% (1/20) in the placebo group (OR 2.27; 95% CI 0.35 to 14.75). A statistically significant benefit for clinical improvement at two weeks was observed. Clinical improvement was observed in 62% (13/21) of patients in the high target serum concentration group, in 36% (8/22) in the low target serum concentration group and in 10% (2/20) in the placebo group (OR 8.66; 95% CI 1.79 to 42.00; RD 0.39; 95% CI 0.20 to 0.59; NNT = 3). Patients in the high serum target concentration group were significantly more likely than placebo patients to experience adverse events related to treatment (P = 0.043). Finger tremor (n = 6) was the most common adverse event in the tacrolimus group. Other adverse events included: gastroenteritis, sepsis, sleepiness, hot flush, headache, queasiness and stomach discomfort. AUTHORS' CONCLUSIONS: Tacrolimus may be effective for short-term clinical improvement in patients with refractory ulcerative colitis. However, these results should be interpreted with caution due to the small number of patients enrolled in the trial and other study limitations. Insufficient treatment and follow-up intervals prevent any conclusions with regard to long term safety and efficacy. The use of tacrolimus in the clinical setting requires careful consideration of risks versus benefits as well as close monitoring for adverse events. More data from well designed and controlled studies are needed to determine the long-term efficacy and safety of tacrolimus.

Panaccione R, Rutgeerts P, Sandborn WJ, Feagan B, Schreiber S, Ghosh S. · Department of Medicine, University of Calgary, Calgary, AB, Canada. · Aliment Pharmacol Ther. · Pubmed #18532990 No free full text.

Abstract: BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the intestine, which frequently require surgery for complications or failure of medical therapy. AIM: To seek evidence and provide direction for clinicians on optimal strategies to enable steroid free remission in inflammatory bowel disease. METHODS: Scientific literature was reviewed using MEDLINIE with a specific focus on medical therapies for inducing and maintaining remission of CD and UC. The results were discussed at a roundtable meeting to reach a consensus on key issues. RESULTS: Several therapies have demonstrated efficacy for the treatment of active, moderate-to-severe CD and UC. These include agents, which induce remission [corticosteroids, infliximab and adalimumab (CD only)] or maintain remission and spare corticosteroids [azathioprine, mercaptopurine, methotrexate (CD only), infliximab and adalimumab (CD only)]. Wide variability exists in the use of these agents. CONCLUSION: Treatment strategy algorithms are developed for use of these therapies that maximize remission and minimize corticosteroid dependence in patients with moderate-to-severe CD and UC.

Sands BE, Sandborn WJ, Feagan B, Löfberg R, Hibi T, Wang T, Gustofson LM, Wong CJ, Vandervoort MK, Hanauer S, Anonymous00103. · MGH Crohn's & Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Gastroenterology. · Pubmed #18602921 No free full text.

Abstract: BACKGROUND & AIMS: Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis. Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis. METHODS: We evaluated the efficacy of granulocyte/monocyte apheresis in a randomized, double-blind, sham-controlled trial in patients with active moderate-to-severe ulcerative colitis (Mayo score 6-11) in community-based and tertiary care centers. As intervention, we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System (JIMRO, Ltd, Takasaki, Japan) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study (N = 168) and in a smaller, companion study of identical design conducted in Europe and Japan (N = 47). RESULTS: In the pivotal study, clinical remission rates (Mayo score 0-2, with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination) were 17% and 11% for the granulocyte/monocyte apheresis (n = 112)- and sham-treatment groups, respectively (n = 56; P = .361). Clinical response (Mayo score reduction of >/=3 points from baseline) was observed in 44% and 39% of patients, respectively (P = .620). Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response, and changes in Mayo and quality-of-life scores. The companion study and pooled data from both studies also yielded similar results. CONCLUSIONS: In this study, granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis.