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      Evidence-based clinical practice guidelines for Crohn’s disease, integrated with formal consensus of experts in Japan

      review-article
      , , , , , , On Behalf of the Guidelines Project Group of the Research Group of Intractable Inflammatory Bowel Disease subsidized by the Ministry of Health, Labour and Welfare of Japan and the Guidelines Committee of the Japanese Society of Gastroenterology
      Journal of Gastroenterology
      Springer Japan
      Crohn’s disease, Guidelines, Practice guidelines, Evidence, Consensus

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          Abstract

          Crohn’s disease is a disorder of unknown etiology and complicated pathogenesis. A substantial amount of evidence has accumulated recently and has been applied to clinical practice. The present guidelines were developed based on recent evidence and the formal consensus of experts relevant to this disease. Here we provide an overview of these guidelines, as follows.

          • Target disease: Crohn’s disease

          • Users: Clinical practitioners in internal medicine, surgery, gastroenterology, and general practice

          • Purpose: To provide appropriate clinical indicators to practitioners

          • Scope of clinical indicators: Concept of Crohn’s disease, epidemiology, classifications, diagnosis, treatment, follow up, and special situations

          • Intervention: Diagnosis (interview, physical examination, clinical laboratory tests, imaging, and pathology) and treatment (lifestyle guidance, drug therapy, nutritional therapy, surgery, etc.)

          • Outcome assessment: Attenuation of symptoms, induction and maintenance of remission, imaging findings, quality of life (QOL), prevention of complications and harm of therapy

          • Methods for developing these guidelines: Described in the text

          • Basis of recommendations: Integration of evidence level and consensus of experts

          • Cost-benefit analysis: Not implemented

          • Evaluation of effectiveness: Yet to be confirmed

          • Status of guidelines: Updated version of the first Guidelines published in 2010

          • Publication sources: Printed publication available and electronic information in preparation

          • Patient information: Not available

          • Date of publication: October 2011

          These guidelines were intended primarily to be used by practitioners in Japan, and the goal of these guidelines is to improve the outcomes of patients with Crohn’s disease.

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          Most cited references157

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          Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial.

          This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index > or =70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score <150) at weeks 26 and 56. The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.
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            A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.

            Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease. We conducted a 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment. All had scores on the Crohn's Disease Activity Index between 220 and 400 (scores can range from 0 to about 600, with higher scores indicating more severe illness). Patients were randomly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications. At four weeks, 81 percent of the patients given 5 mg of cA2 per kilogram (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilogram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogram (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (p<0.001 for the comparison of the cA2 group as a whole with placebo). Thirty-three percent of the patients given cA2 went into remission (defined as a score below 150 on the Crohn's Disease Activity Index), as compared with 4 percent of the patients given placebo (P=0.005). At 12 weeks, 41 percent of the cA2-treated patients (34 of 83) had had a clinical response, as compared with 12 percent of the patients in the placebo group (3 of 25) (P=0.008). The rates of adverse effects were similar in the groups. A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.
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              Infliximab maintenance therapy for fistulizing Crohn's disease.

              Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks. Copyright 2004 Massachusetts Medical Society
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                Author and article information

                Contributors
                +81-3-33531211 , +81-3-33536247 , thibi@z5.keio.jp
                Journal
                J Gastroenterol
                J. Gastroenterol
                Journal of Gastroenterology
                Springer Japan (Japan )
                0944-1174
                1435-5922
                23 October 2012
                23 October 2012
                January 2013
                : 48
                : 1
                : 31-72
                Affiliations
                [ ]Ofuna Chuo Hospital, Kanagawa, Japan
                [ ]Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
                [ ]Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
                [ ]Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
                [ ]Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
                Article
                673
                10.1007/s00535-012-0673-1
                3541931
                23090001
                98aa9324-bfbd-471d-a232-d128b00eed5a
                © The Author(s) 2012
                History
                : 14 August 2012
                : 16 August 2012
                Categories
                Review
                Custom metadata
                © Springer Japan 2013

                Gastroenterology & Hepatology
                crohn’s disease,guidelines,practice guidelines,evidence,consensus
                Gastroenterology & Hepatology
                crohn’s disease, guidelines, practice guidelines, evidence, consensus

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