Gastroenterology

Gastroenterology

Volume 140, Issue 6, May 2011, Pages 1827-1837.e2
Gastroenterology

Conventional Medical Management of Inflammatory Bowel Disease

https://doi.org/10.1053/j.gastro.2011.02.045Get rights and content

Conventional therapies for ulcerative colitis and Crohn's disease (CD) include aminosalicylates, corticosteroids, thiopurines, methotrexate, and anti–tumor necrosis factor agents. A time-structured approach is required for appropriate management. Traditional step-up therapy has been partly replaced during the last decade by potent drugs and top-down therapies, with an accelerated step-up approach being the most appropriate in the majority of patients. When patients are diagnosed with CD or ulcerative colitis, physicians should consider the probable pattern of disease progression so that effective therapy is not delayed. This can be achieved by setting arbitrary time limits for administration of biological therapies, changing therapy from mesalamine in patients with active ulcerative colitis, or using rescue therapy for acute severe colitis. In this review, we provide algorithms with a time-structured approach for guidance of therapy. Common mistakes in conventional therapy include overprescription of mesalamine for CD; inappropriate use of steroids (for perianal CD, when there is sepsis, or for maintenance); delayed introduction or underdosing with azathioprine, 6-mercaptopurine, or methotrexate; and failure to consider timely surgery. The paradox of anti–tumor necrosis factor therapy is that although it too is used inappropriately (when patients have sepsis or fibrostenotic strictures) or too frequently (for diseases that would respond to less-potent therapy), it is also often introduced too late in disease progression. Conventional drugs are the mainstay of current therapy for inflammatory bowel diseases, but drug type, timing, and context must be optimized to manage individual patients effectively.

Section snippets

Approach to Care

The choice of treatment depends on disease activity and extent, as well as patient acceptability and mode of drug delivery. Disease activity is best confirmed (and infection excluded) before therapy is initiated or when response to therapy is slow. To optimize conventional therapy, it is important to carefully time the steps of treatment and explain the strategy to the patient.

Inducing Remission in Patients With UC

5-Aminosalicylates are the most common treatment for patients with mild (≤4 bloody stools/d) or moderately active disease (>4 bloody stools/d without systemic toxicity).6 Absorption must be prevented to achieve colonic delivery, either by administration of a prodrug (balsalazide, olsalazine, or sulfasalazine), a drug with a gastroresistant, pH-dependent coating (eg, Asacol, Salofalk), or a drug with a slow-release mechanism (eg, Pentasa).7 Nevertheless, the asymmetrical, right-to-left gradient

Inducing Remission of Patients With CD

The therapeutic strategies are broadly similar in CD and UC, although significant differences exist, including a limited or lack of response to mesalamine or cyclosporin, response to nutritional therapy, and greater need for surgery in CD.4, 5 Enthusiasm for biological therapy needs to be tempered with recognition that half will have a benign course; in a Norwegian, 10-year, population-based study, just 53% developed stricturing or penetrating disease.34 At diagnosis, it is possible to identify

Maintaining Remission of Patients With UC

In a population-based study of 1575 patients with UC, 13% had no relapse, 74% had ≥2 relapses, and 13% had active disease every year for 5 years after diagnosis.48 Oral mesalamine is the first-line maintenance therapy reducing the risk of relapse by 50% (odds ratio = 0.47 for failure to maintain clinical or endoscopic remission vs placebo).49 Clinical remission with complete discontinuation of corticosteroid use should be the goal of therapy for UC, but the definition of remission varies,

Maintaining Remission in Patients With CD

Cigarette smoking should be discouraged in patients with CD because it increases the need for steroid therapy and surgery.63 Mesalamine cannot be recommended for patients with CD, as results from meta-analyses are inconsistent. A Cochrane review found no benefit of mesalamine (odds ratio = 1.00 for maintaining medically induced remission over 12 months), but there may be differences among delivery systems.64, 65 Steroids should not be used to maintain remission either. Budesonide (6 mg) daily

Perianal CD

Antibiotics reduce fistula drainage, but in a randomized comparison, only 4 of 10 patients responded to ciprofloxacin, compared to 1 of 8 on metronidazole and 1 of 7 on placebo.77 The study was too small to show significant differences, but 5 of 8 could not tolerate metronidazole for 10 weeks. Azathioprine has only been assessed in retrospective studies; fistulae healed in approximately 33% of patients. Complex fistulizing CD warrants early introduction of anti-TNF agents, combined with

Conclusions

Common mistakes in conventional therapy include overprescription of mesalamine for CD, inappropriate use of steroids (for perianal CD in patients with sepsis or for maintenance), delayed introduction or underdosing with immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate), and failure to consider timely surgery. The paradox of anti-TNF therapy is that although it is used inappropriately (when there is sepsis or a fibrostenotic stricture) or overused (for disease that would respond

Acknowledgments

We are grateful to Tim Orchard and Ailsa Hart for their views on the algorithms.

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    Conflicts of interest This author discloses the following: Dr Travis has acted as an advisor to and is in receipt of unrestricted educational grants or speaker's honoraria from: Abbott, Asahi, Ferring, Genzyme, Merck, Novartis, Procter & Gamble, Schering–Plough, Tillotts, and UCB. The remaining author discloses no conflicts.

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