Elsevier

The Lancet

Volume 369, Issue 9573, 12–18 May 2007, Pages 1641-1657
The Lancet

Series
Inflammatory bowel disease: clinical aspects and established and evolving therapies

https://doi.org/10.1016/S0140-6736(07)60751-XGet rights and content

Summary

Crohn's disease and ulcerative colitis are two idiopathic inflammatory bowel disorders. In this paper we discuss the current diagnostic approach, their pathology, natural course, and common complications, the assessment of disease activity, extraintestinal manifestations, and medical and surgical management, and provide diagnostic and therapeutic algorithms. We critically review the evidence for established (5-aminosalicylic acid compounds, corticosteroids, immunomodulators, calcineurin inhibitors) and emerging novel therapies—including biological therapies—directed at cytokines (eg, infliximab, adalimumab, certolizumab pegol) and receptors (eg, visilizumab, abatacept) involved in T-cell activation, selective adhesion molecule blockers (eg, natalizumab, MLN-02, alicaforsen), anti-inflammatory cytokines (eg, interleukin 10), modulation of the intestinal flora (eg, antibiotics, prebiotics, probiotics), leucocyte apheresis and many more monoclonal antibodies, small molecules, recombinant growth factors, and MAP kinase inhibitors targeting various inflammatory cells and pathways. Finally, we summarise the practical aspects of standard therapies including dosing, precautions, and side-effects.

Introduction

Following the discussion of the cause and immunobiology in part 1 of this Series,1 we focus here on the clinical aspects of inflammatory bowel disease.

Section snippets

Definition

Ulcerative colitis is a relapsing non-transmural inflammatory disease that is restricted to the colon. Dependent on the anatomic extent of involvement, patients can be classified as having proctitis, left-sided colitis (involving the sigmoid colon with or without involvement of the descending colon), or pancolitis. A few patients also develop ileal inflammation (backwash ileitis), which occasionally complicates differentiation from Crohn's ileocolitis (table 1). Patients typically present with

Definition

Crohn's disease is a relapsing, transmural inflammatory disease of the gastrointestinal mucosa that can affect the entire gastrointestinal tract from the mouth to the anus. Typical presentations include the discontinuous involvement of various portions of the gastrointestinal tract and the development of complications including strictures, abscesses, or fistulas (table 1 and figure 1). The Vienna classification was developed to describe the distinct clinical phenotypes of Crohn's disease with

Extraintestinal manifestations of inflammatory bowel disease

Up to 25% patients with Crohn's disease and ulcerative colitis will develop extraintestinal disease manifestations or complications (figure 5). Extraintestinal manifestations usually respond to treatment of the underlying disease.

Emerging therapies for inflammatory bowel disease

Advances in knowledge of the immunology of inflammatory bowel disease and in bioengineering have led to new therapeutic concepts that target almost every aspect of the inflammatory process.1 Table 5, Table 6 show agents grouped by underlying therapeutic strategy or concept.

Safety and monitoring of medical treatments for inflammatory bowel disease

Many medical therapies inflammatory bowel disease, particularly immunosuppressants and modulators, are associated with important side-effects. Systemic corticosteroid toxicities include moon face, acne, infection (including increase risk of abdominal and pelvic abscess in patients with Crohn's disease), ecchymoses, hypertension, hirsutism, petechial bleeding, striae, diabetes mellitus, osteonecrosis, osteoporosis, myopathy, psychosis, cataracts, and glaucoma.43, 45 Azathioprine and

Neoplastic complications of inflammatory bowel disease

Patients with ulcerative colitis and Crohn's disease have an increased risk of developing malignancies including colon cancer in patients with ulcerative colitis and Crohn's colitis and small-bowel carcinoma in patients with Crohn's enteritis.159 A screening colonoscopy with a minimum of 30 mucosal biopsies should be done in patients with ulcerative colitis to rule out colonic neoplasia, dysplasia, or cancer, 8–10 years after onset of ulcerative colitis symptoms. Patients with extensive colitis

Search strategy and selection criteria

We searched Medline, Web of Science, and abstracts from major meetings in 2005 and 2006. We used the medical subject heading (MeSH) terms “inflammatory bowel disease”, “ulcerative colitis”, and “Crohn's disease”.

References (163)

  • H Sandberg-Gertzen et al.

    Azodisal sodium in the treatment of ulcerative colitis: a study of tolerance and relapse-prevention properties

    Gastroenterology

    (1986)
  • DS Levine et al.

    A randomized, double blind, dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis

    Am J Gastroenterol

    (2002)
  • SB Hanauer et al.

    Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group

    Gastroenterology

    (1998)
  • JE Lennard-Jones et al.

    Prednisone as maintenance treatment for ulcerative colitis in remission

    Lancet

    (1965)
  • SC Truelove et al.

    Intensive intravenous regimen for severe attacks of ulcerative colitis

    Lancet

    (1974)
  • G Van Assche et al.

    Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis

    Gastroenterology

    (2003)
  • G Jarnerot et al.

    Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study

    Gastroenterology

    (2005)
  • GR Lichtenstein et al.

    American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease

    Gastroenterology

    (2006)
  • WJ Faubion et al.

    The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study

    Gastroenterology

    (2001)
  • G D'Haens et al.

    Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis

    Gastroenterology

    (2001)
  • R Oren et al.

    Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial

    Gastroenterology

    (1996)
  • DF Berg et al.

    Acute surgical emergencies in inflammatory bowel disease

    Am J Surg

    (2002)
  • DW Larson et al.

    Current concepts and controversies in surgery for IBD

    Gastroenterology

    (2004)
  • SB Hanauer et al.

    The Practice Parameters Committee of the American College of Gastroenterology: management of Crohn's disease in adults

    Am J Gastroenterol

    (2001)
  • WJ Sandborn et al.

    A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn's disease

    Gastroenterology

    (2002)
  • T Jess et al.

    Mortality and causes of death in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark

    Gastroenterology

    (2002)
  • RW Summers et al.

    National Cooperative Crohn's Disease Study: results of drug treatment

    Gastroenterology

    (1979)
  • H Malchow et al.

    European Cooperative Crohn's Disease Study: results of drug treatment

    Gastroenterology

    (1984)
  • JW Singleton et al.

    Mesalamine capsules for the treatment of active Crohn's disease: results of a 16-week trial. Pentasa Crohn's Disease Study Group

    Gastroenterology

    (1993)
  • SB Hanauer et al.

    Oral Pentasa in the treatment of active Crohn's disease: a meta-analysis of double-blind, placebo-controlled trials

    Clin Gastroenterol Hepatol

    (2004)
  • C Camma et al.

    Mesalamine in the maintenance treatment of Crohn's disease: a meta- analysis adjusted for confounding variables

    Gastroenterology

    (1997)
  • H Lochs et al.

    Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI

    Gastroenterology

    (2000)
  • AH Steinhart et al.

    Combined budesonide and antibiotic therapy for active Crohn's disease: a randomized controlled trial

    Gastroenterology

    (2002)
  • P Rutgeerts et al.

    Controlled trial of metronidazole treatment for prevention of Crohn's recurrence after ileal resection

    Gastroenterology

    (1995)
  • S Ardizzone et al.

    Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease

    Gastroenterology

    (2004)
  • SB Hanauer et al.

    Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial

    Gastroenterology

    (2004)
  • SB Hanauer et al.

    Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial

    Lancet

    (2002)
  • SB Hanauer et al.

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

    Gastroenterology

    (2006)
  • JF Colombel et al.

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

    Gastroenterology

    (2007)
  • EJ Schoon et al.

    Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease

    Clin Gastroenterol Hepatol

    (2005)
  • NM Thielman et al.

    Clinical practice: acute infectious diarrhoea

    N Engl J Med

    (2004)
  • MJ Carter et al.

    Ibd Section BSoG, Guidelines for the management of inflammatory bowel disease in adults

    Gut

    (2004)
  • A Kornbluth et al.

    Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology Practice Parameters Committee

    Am J Gastroenterol

    (2004)
  • E Langholz et al.

    Changes in extent of ulcerative colitis: a study on the course and prognostic factors

    Scand J Gastroenterol

    (1996)
  • WJ Sandborn et al.

    Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis

    Aliment Pharmacol Ther

    (2003)
  • LR Sutherland et al.

    Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis

    Ann Intern Med

    (1993)
  • SB Hanauer et al.

    Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial

    Am J Gastroenterol

    (2005)
  • CN Williams

    Efficacy and tolerance of 5-aminosalicyalic acid suppositories in the treatment of ulcerative procititis: a review of two double-blind, placebo-controlled trials

    Can J Gastroenterol

    (1990)
  • P Marteau et al.

    Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study

    Gut

    (2005)
  • CA Sninsky et al.

    Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis: a multicenter study

    Ann Intern Med

    (1991)
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