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      About Digestion: 3.2 Impact Factor I 6.4 CiteScore I 0.914 Scimago Journal & Country Rank (SJR)

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      Extraintestinal Manifestations of Crohn’s Disease

      case-report

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          Abstract

          In each case of extraintestinal manifestations of Crohn’s disease, active disease, if present, should be treated to induce remission, which may positively influence the course of most concomitant extraintestinal manifestations. For some extraintestinal manifestations, however, a specific treatment should be introduced. This latter part of disease management will be discussed in this chapter, in particular for pyoderma gangrenosum, uveitis, spondylarthropathy – axial arthropathy – and primary sclerosing cholangitis, which have also been described in quiescent Crohn’s disease. Few new drugs for the treatment of extraintestinal manifestations of Crohn’s disease have been developed in the past and only the role of infliximab has increased in Crohn’s disease-related extraintestinal manifestations. Drugs specifically aimed at this treatment, stemming from a few randomized controlled studies or case series, are sulfasalazine, 5-ASA, corticosteroids, azathioprine or 6-mercaptopurine, methotrexate, infliximab, adalimumab, etanercept and cyclosporine or tacrolimus. Unfortunately, because of the paucity of data in this field, the best evidence presented and discussed in this article for the treatment of these extraintestinal manifestations is extrapolated from patients that for the most part did not suffer from Crohn’s disease.

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          Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial.

          Stephen Hanauer, William J Sandborn, Paul Rutgeerts … (2006)
          Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn's disease (CD). Adalimumab is a human immunoglobulin G1 (IgG(1)) monoclonal antibody targeting tumor necrosis factor (TNF). A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD. A total of 299 patients with moderate to severe CD naive to anti-TNF therapy were randomized to receive subcutaneous injections at weeks 0 and 2 with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg or placebo. The primary endpoint was demonstration of a significant difference in the rates of remission at week 4 (defined as a Crohn's Disease Activity Index score <150 points) among the 80 mg/40 mg, 160 mg/80 mg, and placebo groups. The rates of remission at week 4 in the adalimumab 40 mg/20 mg, 80 mg/40 mg, and 160 mg/80 mg groups were 18% (P = .36), 24% (P = .06), and 36% (P = .001), respectively, and 12% in the placebo group. Adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions, which were more common in adalimumab-treated patients. Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn's disease naive to anti-TNF therapy. The optimal induction dosing regimen for adalimumab in this study was 160 mg at week 0 followed by 80 mg at week 2. Adalimumab was well tolerated.
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            Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial.

            Dorothy Forbes, Tiffany Greenwood, J Bowden … (2006)
            Pyoderma gangrenosum (PG) is a chronic ulcerating skin condition that often occurs in association with inflammatory bowel disease. There have been a number of reports of PG responding to infliximab, a monoclonal antibody against tumour necrosis factor alpha. In the first randomised placebo controlled trial of any drug for the treatment of PG, we have studied the role of infliximab in this disorder. Patients 18 years of age or older with a clinical diagnosis of PG were invited to take part. Patients were randomised to receive an infusion of infliximab at 5 mg/kg or placebo at week 0. Patients were then assessed at week 2 and non-responders were offered open labelled infliximab. The primary end point was clinical improvement at week 2, with secondary end points being remission and improvement at week 6. Thirty patients were entered into the study. After randomisation, 13 patients received infliximab and 17 patients received placebo. At week 2, significantly more patients in the infliximab group had improved (46% (6/13)) compared with the placebo group (6% (1/17); p = 0.025). Overall, 29 patients received infliximab with 69% (20/29) demonstrating a beneficial clinical response. Remission rate at week 6 was 21% (6/29). There was no response in 31% (9/29) of patients. This study has demonstrated that infliximab at a dose of 5 mg/kg is superior to placebo in the treatment of PG. Open label treatment with infliximab also produced promising results. Infliximab treatment should be considered in patients with PG.
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              Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha.

              Brandon Sack, D Gorman, Jennifer Davis (2002)
              There are few effective treatments for ankylosing spondylitis, which causes substantial morbidity. Because of the central role of tumor necrosis factor alpha in the spondyloarthritides, we performed a randomized, double-blind, placebo-controlled trial of etanercept, a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein, in patients with ankylosing spondylitis. Forty patients with active, inflammatory ankylosing spondylitis were randomly assigned to receive twice-weekly subcutaneous injections of etanercept (25 mg) or placebo for four months. The primary end point was a composite of improvements in measures of morning stiffness, spinal pain, functioning, the patient's global assessment of disease activity, and joint swelling. Patients were allowed to continue taking nonsteroidal antiinflammatory drugs, oral corticosteriods (< or =10 mg per day), and disease-modifying antirheumatic drugs at stable doses during the trial. Treatment with etanercept resulted in significant and sustained improvement. At four months, 80 percent of the patients in the etanercept group had a treatment response, as compared with 30 percent of those in the placebo group (P=0.004). Improvements over base-line values for various measures of disease activity, including morning stiffness, spinal pain, functioning, quality of life, enthesitis, chest expansion, erythrocyte sedimentation rate, and C-reactive protein, were significantly greater in the etanercept group. Longitudinal analysis showed that the treatment response was rapid and did not diminish over time. Etanercept was well tolerated, with no significant differences in rates of adverse events between the two groups. Treatment with etanercept for four months resulted in rapid, significant, and sustained improvement in patients with ankylosing spondylitis.
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                Author and article information

                Journal
                Journal ID (publisher-id): DIG
                Journal ID (nlm-ta): Digestion
                Journal ID (doi): 10.1159/issn.0012-2823
                Title: Digestion
                Publisher: S. Karger AG
                ISBN: 978-3-8055-8469-2
                ISBN: 978-3-8055-8470-8
                ISSN (Print): 0012-2823
                ISSN (Electronic): 1421-9867
                Publication date Subscription-year: 2007
                Publication date (Print): February 2008
                Publication date (Electronic): 07 February 2008
                Volume: 76
                Issue: 2
                Pages: 141-148
                Affiliations
                aDivision of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, bGastrointestinal Department, University of Basle, Basle, and cHealthcare Evaluation Unit, Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland
                Article
                Publisher ID: 111029 Other ID: Digestion 2007;76:141–148
                DOI: 10.1159/000111029
                PubMed ID: 18239406
                SO-VID: 846e0390-6ee3-433f-8c52-87f6c35065af
                Copyright © © 2008 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                References: 106, Pages: 8
                Categories
                Subject: Paper

                ScienceOpen disciplines: Oncology & Radiotherapy,Gastroenterology & Hepatology,Surgery,Nutrition & Dietetics,Internal medicine
                Keywords: Ankylosing spondylitis,Pyoderma gangrenosum,Crohn’s disease,Extraintestinal manifestations,Inflammatory bowel disease,Primary sclerosing cholangitis,Crohn’s disease, extraintestinal manifestations,Uveitis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Gastroenterology & Hepatology, Surgery, Nutrition & Dietetics, Internal medicine
                Keywords: Ankylosing spondylitis, Pyoderma gangrenosum, Crohn’s disease, Extraintestinal manifestations, Inflammatory bowel disease, Primary sclerosing cholangitis, Crohn’s disease, extraintestinal manifestations, Uveitis

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