Why Mesalamine is Not Effective for Crohn's Disease
The AGA strongly recommends against using mesalamine or sulfasalazine for moderate to severe Crohn's disease because multiple randomized controlled trials demonstrate no benefit for maintaining remission, and starting an ineffective drug delays appropriate therapy and worsens disease outcomes. 1
The Evidence Against Mesalamine in Crohn's Disease
Lack of Efficacy for Maintenance of Remission
The most compelling evidence comes from systematic reviews showing mesalamine fails to maintain remission in Crohn's disease:
11 randomized controlled trials with 2,014 patients found mesalamine no more effective than placebo for maintenance of remission (RR 1.02; 95% CI 0.92-1.16), with moderate certainty evidence 1
A Cochrane systematic review confirmed oral 5-ASA has no efficacy in maintaining clinical remission in Crohn's disease, with similar negative findings across multiple meta-analyses 1
Marginal to No Benefit for Induction of Remission
For inducing remission, the data are equally disappointing:
Two RCTs comparing mesalamine to placebo for induction failed to reach the minimal clinically important difference of 10% over placebo (RR 0.90; 95% CI 0.81-1.00) 1
High-dose mesalamine (3-4.5 g/day) was not superior to placebo for inducing remission (RR 2.02; 95% CI 0.75 to 5.45) or response 2
Low-dose mesalamine (1-2 g/day) was not superior to placebo (RR 1.46; 95% CI 0.89-2.40) 2
The British Society of Gastroenterology Position
The BSG explicitly states: "We recommend that mesalazine is not used" for Crohn's disease, based on Cochrane reviews showing no benefit for either induction or maintenance 1
Why This Differs from Ulcerative Colitis
The fundamental difference lies in disease pathophysiology and drug mechanism:
Mesalamine is highly effective for ulcerative colitis, where the AGA strongly recommends standard-dose mesalamine (2-3 grams/day) as first-line therapy for mild-moderate disease 1
In UC, mesalamine works through topical anti-inflammatory action on superficial mucosal inflammation 1
Crohn's disease involves transmural inflammation (through the entire bowel wall), which mesalamine cannot adequately address even with controlled-release formulations designed to deliver drug throughout the small bowel and colon 3
Clinical Implications and Pitfalls
The Danger of Using Ineffective Therapy
The AGA panel emphasized that starting a drug ineffective for induction leads to delays in appropriate therapy and worsening disease 1
This is critical because:
Patients with moderate to severe Crohn's disease require effective therapy to prevent complications (strictures, fistulas, abscesses) 1
Most drugs started for induction should be continued for maintenance, so beginning with an ineffective agent creates a therapeutic dead-end 1
Common Prescribing Error
Despite clear evidence, UK data from 1990-2010 showed over half of Crohn's disease patients were prescribed 5-ASA, often for Crohn's colitis 1
This represents a significant quality gap in care, as even colonic Crohn's disease does not benefit from mesalamine 1
Note on Sulfasalazine
While sulfasalazine showed modest benefit in some older trials (RR 0.78; 95% CI 0.65-0.93 for induction), it:
- Failed to maintain remission (RR 0.98; 95% CI 0.82-1.17) with very low certainty evidence 1
- Is associated with many adverse events compared to mesalamine's robust safety profile 1
- Is inferior to corticosteroids (RR 0.66; 95% CI 0.53 to 0.81) 2
What Should Be Used Instead
For moderate to severe Crohn's disease, evidence-based alternatives include:
- Biologic therapies: Infliximab is strongly recommended for both luminal and fistulizing disease 1
- Immunomodulators: Thiopurines or methotrexate (at least 15 mg weekly, subcutaneous route preferred) 1
- Corticosteroids: For induction only, not maintenance 1
Combination therapy with infliximab plus a thiopurine is more effective than monotherapy for induction and maintenance 1