Aminosalicylates for Crohn's Ileitis
Aminosalicylates (5-ASA) are NOT effective for Crohn's ileitis and should not be used. The most recent high-quality guidelines explicitly recommend against their use in this setting.
Primary Recommendation
The American Gastroenterological Association (AGA) strongly recommends against the use of 5-ASA (mesalamine) or sulfasalazine for the induction or maintenance of remission in Crohn's disease, with moderate-quality evidence 1. This recommendation applies to all locations of Crohn's disease, including ileitis.
Evidence Base
Mesalamine (5-ASA) Formulations
Oral mesalamine at any dose is ineffective for Crohn's ileitis 2. The Canadian Association of Gastroenterology guidelines suggest against the use of oral 5-ASA to induce OR maintain complete remission in Crohn's disease of any severity (conditional recommendation, low-quality evidence for induction, moderate-quality evidence for maintenance) 2.
Low-dose mesalamine (1-2 g/day) is not superior to placebo for inducing remission, with only 23% achieving remission compared to 15% with placebo (RR 1.46,95% CI 0.89 to 2.40) 3.
High-dose mesalamine (4 g/day) is also ineffective, showing only a clinically non-significant reduction in CDAI scores (MD -19.8 points, 95% CI -46.2 to 6.7) and was inferior to budesonide 3.
Sulfasalazine
Sulfasalazine shows only modest benefit in Crohn's disease, and this benefit is confined to colonic disease, NOT ileitis 2, 3. The Canadian guidelines suggest sulfasalazine (4-6 g/day) only for patients with mild Crohn's disease limited to the colon (conditional recommendation, very low-quality evidence) 2.
For ileitis specifically, sulfasalazine is ineffective because it requires colonic bacteria to cleave the azo bond and release 5-ASA 2, 4. In isolated ileal disease, this mechanism cannot occur, rendering the drug ineffective 5.
Historical data from 1984 confirms that sulfasalazine "appears to be of greater benefit to patients with colitis and ileocolitis than those with ileitis alone" 5.
Recommended Alternative Therapy
For mild-to-moderate ileal or right colonic Crohn's disease, oral budesonide 9 mg/day is the recommended first-line therapy 2. The Canadian guidelines suggest this as first-line therapy to induce complete remission (conditional recommendation, low-quality evidence) 2.
- Patients should be evaluated for symptomatic response to budesonide between 4 and 8 weeks to determine the need to modify therapy 2.
Special Considerations for Sulfa Allergy and Renal Impairment
Sulfa Allergy
Patients with known sulfa allergy should NOT receive sulfasalazine 6. This is a contraindication as sulfasalazine contains sulfapyridine, which causes most adverse effects 4.
Mesalamine formulations do NOT contain sulfa and can be safely used in patients with sulfa allergy 2. However, as noted above, mesalamine is ineffective for Crohn's ileitis regardless of allergy status.
Renal Impairment
All aminosalicylates carry risk of nephrotoxicity 2, 7. The FDA label for mesalamine requires evaluation of renal function prior to initiation and periodically during treatment 7.
In patients with known renal impairment, the risks and benefits of mesalamine must be carefully evaluated 7. However, since mesalamine is ineffective for ileitis, this consideration is moot—these patients should receive alternative therapy (budesonide) rather than any aminosalicylate 2.
Rare cases of tubulointerstitial nephritis can occur with all 5-ASA preparations 2, 8.
Clinical Algorithm
- Confirm disease location: Ileitis or ileocolonic disease
- Do NOT prescribe aminosalicylates (mesalamine or sulfasalazine) for ileal involvement 2, 1
- Initiate budesonide 9 mg/day for mild-to-moderate disease 2
- Assess response at 4-8 weeks 2
- If inadequate response, escalate to prednisone 40-60 mg/day for moderate disease 2
- Consider early biologic therapy for moderate-to-severe disease or high-risk features 1
Common Pitfall
The most critical pitfall is prescribing aminosalicylates for Crohn's ileitis based on outdated practice patterns or confusion with ulcerative colitis management 1, 3. While 5-ASA agents are highly effective for ulcerative colitis 2, they have no role in Crohn's ileitis. The evidence is clear and consistent across multiple high-quality guidelines from 2019 that aminosalicylates should not be used for any location of Crohn's disease 2, 1.