Skip to main content
SpringerLink
Log in

Conventional Medical Management of Crohn’s Disease: Sulfasalazine

  • Chapter
  • First Online:
Crohn's Disease and Ulcerative Colitis

Abstract

Sulfasalazine (SASP) is a prodrug composed of a molecule of 5-aminosalicylic acid (5-ASA) and sulfapyridine, linked by an azo bond. When taken orally anaerobic intestinal bacteria split the azo bond, releasing the two components 5-ASA and sulfapyridine, the former being the active anti-inflammatory component. It has been reported that SASP and its metabolites therapeutically act in different points in the inflammatory cascade by decreasing eicosanoid synthesis, cytokine expression, and the activation of NF-kB transcription factor. In addition, SASP exhibit antioxidant activity.

SASP has been used in ulcerative colitis where it has been shown to be effective in both inducing remission of active disease and preventing relapse in inactive patients. However, the role of SASP in the treatment of mild or moderate Crohn’s disease is controversial still nowadays. The first solid evaluation of the effect of SASP on Crohn’s disease comes from two ancient large studies: the American National Cooperative Crohn’s Disease Study (NCCDS) and the European Cooperative Crohn’s Disease Study (ECCDS).

Two meta-analyses pooling the available data on the effect of different salicylates in mild-to-moderate active Crohn’s disease showed that SASP was marginally effective in inducing remission compared to placebo, with benefit confined mainly to patients with isolate colonic involvement. Interestingly, however, the performance of SASP was better than that of mesalazine, either at low or high dose. In contrast, mesalazine but not SASP has shown to be effective in the prevention of postoperative recurrence in Crohn’s disease.

On the light of the available evidence, both experts and consensus-based guidelines recommend the use of high-dose (3–6 g/day) SASP in Crohn’s disease only for patients with mild disease confined to the colon. Anyway, SASP should be used in the short term, and active disease beyond 16 weeks of this therapy should be considered a therapeutic failure.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Azad Khan AK, Piris J, Truelove SC. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet. 1977;2:892–5.

    Article  CAS  PubMed  Google Scholar 

  2. Goldman P, Peppercorn MA. Drug therapy: sulfasalazine. N Engl J Med. 1975;293:20–3.

    Article  CAS  PubMed  Google Scholar 

  3. Das KM, Dubin R. Clinical pharmacokinetics of sulphasalazine. Clin Pharmacokinet. 1976;1:406–25.

    Article  CAS  PubMed  Google Scholar 

  4. Rieder F, Karrasch T, Ben-Horin S, Schirbel A, Ehehalt R, Wehkamp J, et al. Results of the 2nd scientific workshop of the ECCO (III): basic mechanisms of intestinal healing. J Crohns Colitis. 2012;6:373–85.

    Article  PubMed  Google Scholar 

  5. Hawkey CJ, Boughton-Smith NK, Whittle BJ. Modulation of human colonic arachidonic acid metabolism by sulfasalazine. Dig Dis Sci. 1985;30:1161–5.

    Article  CAS  PubMed  Google Scholar 

  6. Ahnfelt-Ronne I, Nielsen OH, Bukhave K, Elmgreen J. Sulfasalazine and its anti-inflammatory metabolite, 5-aminosalicylic acid: effect on arachidonic acid metabolism in human neutrophils, and free radical scavenging. Adv Prostaglandin Thromboxane Leukot Res. 1987;17B:918–22.

    CAS  PubMed  Google Scholar 

  7. Tornhamre S, Edenius C, Smedegard G, Sjoquist B, Lindgren JA Effects of sulfasalazine and a sulfasalazine analogue on the formation of lipoxygenase and cyclooxygenase products. Eur J Pharmacol. 1989;169:225–34.

    Article  CAS  PubMed  Google Scholar 

  8. Rachmilewitz D, Karmeli F, Schwartz LW, Simon PL. Effect of aminophenols (5-ASA and 4-ASA) on colonic interleukin-1 generation. Gut. 1992;33:929–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Stevens C, Lipman M, Fabry S, Moscovitch-Lopatin M, Almawi W, Keresztes S, et al. 5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin-2 production in peripheral blood mononuclear cells. J Pharmacol Exp Ther. 1995;272:399–406.

    CAS  PubMed  Google Scholar 

  10. Hasko G, Szabo C, Nemeth ZH, Deitch EA. Sulphasalazine inhibits macrophage activation: inhibitory effects on inducible nitric oxide synthase expression, interleukin-12 production and major histocompatibility complex II expression. Immunology. 2001;103:473–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gan HT, Chen YQ, Ouyang Q. Sulfasalazine inhibits activation of nuclear factor-kappaB in patients with ulcerative colitis. J Gastroenterol Hepatol. 2005;20:1016–24.

    Article  CAS  PubMed  Google Scholar 

  12. Wahl C, Liptay S, Adler G, Schmid RM. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest. 1998;101:1163–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Miles AM, Grisham MB. Antioxidant properties of aminosalicylates. Methods Enzymol. 1994;234:555–72.

    Article  CAS  PubMed  Google Scholar 

  14. Joshi R, Kumar S, Unnikrishnan M, Mukherjee T. Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: mechanistic aspects and antioxidant activity. Free Radic Res. 2005;39:1163–72.

    Article  CAS  PubMed  Google Scholar 

  15. Couto D, Ribeiro D, Freitas M, Gomes A, Lima JL, Fernandes E. Scavenging of reactive oxygen and nitrogen species by the prodrug sulfasalazine and its metabolites 5-aminosalicylic acid and sulfapyridine. Redox Rep. 2010;15:259–67.

    Article  CAS  PubMed  Google Scholar 

  16. Dignass A, van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis. 2010;4:28–62.

    Article  CAS  PubMed  Google Scholar 

  17. Jones JH, Lennard-Jones JE, Lockhart-Mummery HE. Experience in the treatment of Crohn’s disease of the large intestine. Gut. 1966;7:448–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Goldstein F, Murdock MG. Clinical and radiologic improvement of regional enteritis and enterocolitis after treatment with salicylazosulfapyridine. Am J Dig Dis. 1971;16:421–31.

    Article  CAS  PubMed  Google Scholar 

  19. Anthonisen P, Barany F, Folkenborg O, Holtz A, Jarnum S, Kristensen M, et al. The clinical effect of salazosulphapyridine (Salazopyrin r) in Crohn’s disease. A controlled double-blind study. Scand J Gastroenterol. 1974;9:549–54.

    CAS  PubMed  Google Scholar 

  20. Lennard-Jones JE. Sulphasalazine in asymptomatic Crohn’s disease. A multicentre trial. Gut. 1977;18:69–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Singleton JW, Summers RW, Kern Jr F, Becktel JM, Best WR, Hansen RN, et al. A trial of sulfasalazine as adjunctive therapy in Crohn’s disease. Gastroenterology. 1979;77:887–97.

    CAS  PubMed  Google Scholar 

  22. Summers RW, Switz DM, Sessions JT, Becketel JM, Best WR, Kern F, et al. National cooperative Crohn’s disease study: results of drug treatment. Gastroenterology. 1979;77:847–69.

    CAS  PubMed  Google Scholar 

  23. Malchow H, Ewe K, Brandes JW, Goebell H, Ehms H, Sommer H, et al. European Cooperative Crohn’s Disease Study (ECCDS): results of drug treatment. Gastroenterology. 1984;86:249–66.

    CAS  PubMed  Google Scholar 

  24. Rijk MC, Van Hogezand RA, van Lier HJ, van Tongeren JH. Sulphasalazine and prednisone compared with sulphasalazine for treating active Crohn disease. A double-blind, randomized, multicenter trial. Ann Intern Med. 1991;114:445–50.

    Article  CAS  PubMed  Google Scholar 

  25. Van Hees PA, van Lier HJ, Van Elteren PH, Driessen M, Van Hogezand RA, Ten Velde GP, et al. Effect of sulphasalazine in patients with active Crohn’s disease: a controlled double-blind study. Gut. 1981;22:404–9.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lim WC, Hanauer S. Aminosalicylates for induction of remission or response in Crohn’s disease. Cochrane Database Syst Rev. 2010;12:CD008870.

    Google Scholar 

  27. Ford AC, Kane SV, Khan KJ, Achkar JP, Talley NJ, Marshall JK, et al. Efficacy of 5-aminosalicylates in Crohn’s disease: systematic review and meta-analysis. Am J Gastroenterol. 2011;106:617–29.

    Article  CAS  PubMed  Google Scholar 

  28. Bergman L, Krause U. Postoperative treatment with corticosteroids and salazosulphapyridine (Salazopyrin) after radical resection for Crohn’s disease. Scand J Gastroenterol. 1976;11:651–6.

    CAS  PubMed  Google Scholar 

  29. Ewe K, Holtermüller KH, Baas U, Eckhart V, Krieg H, Kutzner J, et al. Rezidivprophylaxe nach darmresektion wegen morbus Crohn durch salazosulfapyridin (Azulfidine): eine doppelblindstudie. Verh Dtsch Ges Inn Med. 1976;82:930–2.

    PubMed  Google Scholar 

  30. Wenckert A, Kristensen M, Eklund AE, Barany F, Jarnum S, Worning H, et al. The long-term prophylactic effect of salazosulphapyridine (Salazopyrin) in primarily resected patients with Crohn’s disease. A controlled double-blind trial. Scand J Gastroenterol. 1978;13:161–7.

    Article  CAS  PubMed  Google Scholar 

  31. Ewe K, Herfarth C, Malchow H, Jesdinsky HJ. Postoperative recurrence of Crohn’s disease in relation to radicality of operation and sulfasalazine prophylaxis: a multicenter trial. Digestion. 1989;42:224–32.

    Article  CAS  PubMed  Google Scholar 

  32. Ford AC, Khan KJ, Talley NJ, Moayyedi P. 5-Aminosalicylates prevent relapse of Crohn’s disease after surgically induced remission: systematic review and meta-analysis. Am J Gastroenterol. 2011;106:413–20.

    Article  CAS  PubMed  Google Scholar 

  33. Sandborn WJ, Feagan BG. Review article: mild to moderate Crohn’s disease—defining the basis for a new treatment algorithm. Aliment Pharmacol Ther. 2003;18:263–77.

    Article  CAS  PubMed  Google Scholar 

  34. Gionchetti P, Calabrese C, Tambasco R, Brugnera R, Straforini G, Liguori G, et al. Role of conventional therapies in the era of biological treatment in Crohn’s disease. World J Gastroenterol. 2011;17:1797–806.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Nielsen OH, Munck LK. Drug insight: aminosalicylates for the treatment of IBD. Nat Clin Pract Gastroenterol Hepatol. 2007;4:160–70.

    Article  CAS  PubMed  Google Scholar 

  36. Chen J, Lin S, Liu C. Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst Rev. 2014;11:CD004800.

    Google Scholar 

  37. Das KM, Eastwood MA, McManus JP, Sircus W. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med. 1973;289:491–5.

    Article  CAS  PubMed  Google Scholar 

  38. Taffet SL, Das KM. Sulfasalazine. Adverse effects and desensitization. Dig Dis Sci. 1983;28:833–42.

    Article  CAS  PubMed  Google Scholar 

  39. Franklin JL, Rosenberg HH. Impaired folic acid absorption in inflammatory bowel disease: effects of salicylazosulfapyridine (Azulfidine). Gastroenterology. 1973;64:517–25.

    CAS  PubMed  Google Scholar 

  40. Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. N Engl J Med. 1981;305:1513–7.

    Article  CAS  PubMed  Google Scholar 

  41. Gisbert JP, Gonzalez-Lama Y, Mate J. 5-Aminosalicylates and renal function in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis. 2007;13:629–38.

    Article  PubMed  Google Scholar 

  42. de Jong DJ, Tielen J, Habraken CM, Wetzels JF, Naber AH. 5-Aminosalicylates and effects on renal function in patients with Crohn’s disease. Inflamm Bowel Dis. 2005;11:972–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Health Science Research Institute, Germans Trias i Pujol Foundation, Badalona, Catalonia, Spain

    Miquel A. Gassull M.D., Ph.D.

  2. Gastroenterology and Hepatology Department, Germans Trias I Pujol University Hospital, Badalona, Catalonia, Spain

    Miquel A. Gassull M.D., Ph.D.

  3. IBD/G-I Unit, Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain

    Eduard Cabré M.D., Ph.D.

  4. CIBERehd, Barcelona, Catalonia, Spain

    Eduard Cabré M.D., Ph.D.

Authors
  1. Miquel A. Gassull M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduard Cabré M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miquel A. Gassull M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Charité Medical School—Humboldt-University of Berlin, Berlin, Germany

    Daniel C. Baumgart

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Gassull, M.A., Cabré, E. (2017). Conventional Medical Management of Crohn’s Disease: Sulfasalazine. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Cham. https://doi.org/10.1007/978-3-319-33703-6_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-33703-6_28

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-33701-2

  • Online ISBN: 978-3-319-33703-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation