Significance of 5-Aminosalicylic Acid Intolerance in the Clinical Management of Ulcerative Colitis

Digestion. 2023;104(1):58-65. doi: 10.1159/000527452. Epub 2022 Nov 10.

Abstract

Background: Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for ulcerative colitis. Recent reports show that optimization of 5-ASA therapy is beneficial for both patient outcomes and healthcare costs. Although 5-ASA and SASP have good efficacy and safety profiles, clinicians occasionally encounter patients who develop 5-ASA intolerance.

Summary: The most common symptoms of acute 5-ASA intolerance syndrome are exacerbation of diarrhea, fever, and abdominal pain. Patients who discontinue 5-ASA therapy because of intolerance have a higher risk of adverse clinical outcomes, such as hospital admission, colectomy, need for advanced therapies, and loss of response to anti-tumor necrosis factor (TNF) biologics. When patients develop symptoms of 5-ASA intolerance, the clinician should consider changing the type of 5-ASA preparation. Recent genome-wide association studies and meta-analyses have shown that 5-ASA allergy is associated with certain single-nucleotide polymorphisms. Although there are no modalities or biomarkers for diagnosing 5-ASA intolerance, the drug-induced lymphocyte stimulation test can be used to assist in the diagnosis of acute 5-ASA intolerance syndrome with high specificity and low sensitivity. This review presents a general overview of 5-ASA and SASP in the treatment of inflammatory bowel disease and discusses the latest insights into 5-ASA intolerance.

Key messages: 5-ASA is used as first-line therapy for ulcerative colitis. Optimization of 5-ASA may be beneficial for patient outcomes and healthcare systems. Acute 5-ASA intolerance syndrome is characterized by diarrhea, fever, and abdominal pain. Periodic renal function monitoring is recommended for patients receiving 5-ASA.

Keywords: 5-Aminosalicylic acid; 5-Aminosalicylic acid intolerance; Inflammatory bowel disease; Mesalazine; Ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Abdominal Pain / drug therapy
  • Administration, Oral
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Colitis, Ulcerative* / drug therapy
  • Fever / drug therapy
  • Genome-Wide Association Study
  • Humans
  • Mesalamine* / adverse effects
  • Remission Induction
  • Sulfasalazine / adverse effects

Substances

  • Mesalamine
  • Anti-Inflammatory Agents, Non-Steroidal
  • Sulfasalazine

Grants and funding

This research was funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI (A) 20H00536 for T.K., (B) 20H03666 for Y.M., and a Grant-in-Aid for Early Career Scientists (22K16005 to H.K.); Advanced Research and Development Programs for Medical Innovation (the Practical Research Project for Rare/Intractable Disease; 21ek0109556h0001 to Y.M.); and the Keio University Medical Fund.