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Drug Insight: aminosalicylates for the treatment of IBD

Abstract

Sulfasalazine and mesalazine (also known as mesalamine; 5-aminosalicylic acid) preparations have for many years been used for the treatment of IBD (i.e. ulcerative colitis and Crohn's disease), for both active disease and the control of remission. It has also been suggested that mesalazine is a chemoprophylactic agent that protects against the development of colorectal cancer. This Review focuses on the latest clinical evidence for the use of these aminosalicylates for the treatment of IBD, and concludes that sulfasalazine and mesalazine are useful for the treatment of both active and quiescent ulcerative colitis, whereas they have no clinical effect on either active or inactive Crohn's disease. Furthermore, evidence is lacking that mesalazine per se is a chemoprophylactic agent.

Key Points

  • There is robust evidence from randomized, controlled studies in favor of SASP or 5-ASA as a first-line therapy for the management of active mild to moderate ulcerative colitis and for maintaining remission

  • SASP is modestly effective for the treatment of active mild Crohn's disease; by contrast, 5-ASA is devoid of clinical effect on active Crohn's disease and on maintenance of medically and surgically induced remission

  • Given current knowledge, the many expert reviews and gastrointestinal society guidelines that support the role of SASP and 5-ASA in Crohn's disease need to be examined critically, with greatest reliance placed on high-quality individual studies and full acknowledgment of the limitations of meta-analyses

  • Evidence is lacking that 5-ASA per se is a chemoprophylactic agent, and it is therefore debatable whether maintained 5-ASA treatment in patients with IBD but without inflammation has the potential to reduce their risk of cancer development

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Figure 1: The chemical structure of sulfasalazine (with the azo bond) and mesalazine
Figure 2: Inflammatory mediators and other factors in the diseased intestine that are affected by sulfasalazine or mesalazine
Figure 3: The mechanism of action of mesalazine in the colon
Figure 4: Incidence of colorectal cancer in patients with ulcerative colitis from a meta-analysis of published observational studies83 and a subsequent analysis of the risk in Copenhagen County87

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Acknowledgements

The preparation of this paper has been supported by grants from the Danish Research Agency and the Augustinus Foundation. The authors appreciate the skillful assistance of L Ferrero-Miliani in preparing the illustrations.

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Correspondence to Ole H Nielsen.

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Nielsen, O., Munck, L. Drug Insight: aminosalicylates for the treatment of IBD. Nat Rev Gastroenterol Hepatol 4, 160–170 (2007). https://doi.org/10.1038/ncpgasthep0696

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