Which non‑steroidal agents can be prescribed in primary care for Crohn’s disease and ulcerative colitis?

Non-Steroidal Medications for IBD in Primary Care

For mild to moderate Crohn's disease and ulcerative colitis in primary care, aminosalicylates (mesalazine/5-ASA) are the primary non-steroidal first-line agents, with azathioprine/mercaptopurine serving as steroid-sparing maintenance therapy.

Ulcerative Colitis

Active Disease Treatment

Aminosalicylates (5-ASA compounds):

• Mesalazine 2-4 g daily is first-line therapy for mild to moderately active left-sided or extensive UC 1
• Balsalazide 6.75 g daily is equally effective as an alternative 1
• Olsalazine 1.5-3 g daily can be used but has higher incidence of diarrhea in pancolitis; best reserved for left-sided disease 1
• Sulphasalazine 2-4 g daily is effective but has higher side effect rates compared to newer 5-ASA drugs; may benefit selected patients with reactive arthropathy 1

For distal colitis (proctitis/left-sided):

• Topical mesalazine 1 g daily combined with oral mesalazine 2-4 g daily is most effective first-line therapy 1
• Topical formulation should match disease extent: suppositories for disease to recto-sigmoid junction, foam or liquid enemas for more proximal disease 1

Maintenance Therapy

Immunomodulators for steroid-dependent disease:

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day should be used for patients with chronic active steroid-dependent disease to avoid long-term steroid use 1
• Lifelong maintenance therapy with aminosalicylates is generally recommended, especially for left-sided or extensive disease 1

Crohn's Disease

Active Disease Treatment

Aminosalicylates:

• High-dose mesalazine 4 g daily may be sufficient initial therapy for mild ileocolonic CD 1
• Sulphasalazine 4 g daily is effective for active colonic disease but not recommended as first-line due to high side effect incidence 1
• Topical mesalazine may be effective in left-sided colonic CD of mild to moderate activity 1

Important caveat: Most guidelines are critical of 5-ASA use in mild Crohn's disease, with evidence showing limited effectiveness compared to UC 2, 3. However, there is some evidence for sufficiently high-dose treatment, and clear evidence supports postoperative use in mild recurrence 3.

Antibiotics (for specific indications):

• Metronidazole 10-20 mg/kg/day (400 mg three times daily) is first-line for simple perianal fistulae 1
• Ciprofloxacin 500 mg twice daily can be used alone or combined with metronidazole for perianal disease 1
• Metronidazole has a role in selected patients with colonic or treatment-resistant disease, though not recommended as first-line due to side effects 1

Maintenance and Steroid-Sparing Therapy

Immunomodulators:

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day serve as adjunctive therapy and steroid-sparing agents 1
• Critical limitation: Slow onset of action precludes use as sole therapy for active disease 1
• Effective for simple perianal fistulae or enterocutaneous fistulae where obstruction and abscess have been excluded 1

Common Pitfalls and Caveats

NSAID Use Warning

Avoid NSAIDs in IBD patients: Regular NSAID use (≥5 times/month) is associated with increased risk of disease exacerbation, particularly in Crohn's disease 4, 5. Non-selective NSAIDs cause 17-28% relapse rate within 9 days in quiescent IBD 5. The mechanism appears related to dual COX-1 and COX-2 inhibition 5. Emergency hospital admissions for IBD colitis are associated with NSAID use 6.

Practical Implementation in Primary Care

When to refer versus treat:

• Primary care can initiate aminosalicylates for mild disease 1
• Moderate to severe disease requires gastroenterology consultation 1
• Severe UC (meeting Truelove and Witts' criteria) requires hospital admission and joint medical-surgical management 1

Monitoring considerations:

• Azathioprine/mercaptopurine require monitoring for bone marrow suppression and hepatotoxicity (not detailed in guidelines but standard practice)
• Disease activity should be confirmed by sigmoidoscopy before treatment 1
• Infection should be excluded, though treatment need not wait for microbiological results 1

Newer agents beyond primary care scope:

• Biologics (infliximab, vedolizumab, ustekinumab, risankizumab) and small molecules (upadacitinib) are effective but typically initiated by specialists 7, 2
• These agents are reserved for moderate to severe disease, steroid-refractory cases, or after failure of conventional therapy 7, 2