Crohn Disease: Sutherland L

Panaccione R, Fedorak RN, Aumais G, Bernstein CN, Bitton A, Croitoru K, Enns R, Feagan B, Fishman M, Greenberg G, Griffiths A, Marshall JK, Rasul I, Sadowski D, Seidman E, Steinhart H, Sutherland L, Walli E, Wild G, Williams CN, Zachos M, Anonymous00234. · University of Calgary, Calgary, Canada. · Can J Gastroenterol. · Pubmed #15372114 links to  free full text

This publication has no abstract.

Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C. · Division of Gastroenterology, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. · Cochrane Database Syst Rev. · Pubmed #10796557 No free full text.

Abstract: OBJECTIVES: To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease. SEARCH STRATEGY: Studies were selected using the MEDLINE data base (1966 - December 1997), abstracts from major gastrointestinal meetings and references from published articles and reviews. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register was also searched. SELECTION CRITERIA: Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel ('Odds Ratio' in MetaView). MAIN RESULTS: The odds ratio of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.36 (95% CI 1.57-3.53). This corresponded to a number needed to treat of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the odds ratio of response was 2.04 (CI 1.24 - 3.35). Treatment >/= 17 weeks increased the odds ratio of a response to 2.51 (CI 1.63-3. 88). A steroid sparing effect was seen with an odds ratio of 3.86 (CI 2.14 - 6.96), corresponding to a number needed to treat of about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased on therapy with an odds ratio of 3.01 (CI 1.30 - 6.96). The number needed to treat to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14. REVIEWER'S CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The odds ratio of response increases after >/= 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on therapy.

Feagan BG, Fedorak RN, Irvine EJ, Wild G, Sutherland L, Steinhart AH, Greenberg GR, Koval J, Wong CJ, Hopkins M, Hanauer SB, McDonald JW. · London Clinical Trials Research Group, the John P. Robarts Research Institute, London, Ont, Canada. · N Engl J Med. · Pubmed #10833208 links to  free full text

Abstract: BACKGROUND: Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known. METHODS: We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remission in the methotrexate group, as compared with 14 (39 percent) in the placebo group (P=0.04; absolute reduction in the risk of relapse, 26.1 percent; 95 percent confidence interval, 4.4 percent to 47.8 percent). Fewer patients in the methotrexate group than in the placebo group required prednisone for relapse (11 of 40 [28 percent] vs. 21 of 36 [58 percent], P=0.01). None of the patients who received methotrexate had a severe adverse event; one patient in this group withdrew because of nausea. CONCLUSIONS: In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.

Brant R, Sutherland L, Hilsden R. · Department of Community Health Sciences, Health Sciences Centre, University of Calgary, 3330 Hospital Dr., N. W. Calgary, Alberta, Canada T2N 4N1. · Stat Med. · Pubmed #10495458 No free full text.

Abstract: The increasing use of constructed scales and indices in clinical science has preceded in many cases a clear understanding of how to appraise the importance of the differences or changes that are thereby observed. For example, in the design of clinical trials which employ such scales as outcome measures it may be difficult to specify what constitutes a clinically significant shift in means, a key factor in sample size calculations. Determination of the minimum important difference relative to specific outcome measures has historically been based on informal and/or intuitive arguments. In this paper we propose a formal statistical framework for these considerations, based on a previously published validation study design which captures patients' perceptions in comparative self-reported assessments. We begin by adopting a mixed-effect model to represent the comparative assessments as composites of individual self-ratings on an underlying continuous scale. We then present two basic approaches for assessing the relation between the hypothesized latent scale and the outcome scale(s) under consideration, taking the latent scale as a plausible benchmark against which observable changes on the outcome scale can be judged.