What to add to the treatment regimen for a patient with Crohn's disease on steroids with patchy colitis not responding to treatment?

Treatment Recommendation for Steroid-Refractory Crohn's Disease with Patchy Colitis

Add azathioprine or mercaptopurine as first-line immunomodulation for this steroid-refractory Crohn's disease, with infliximab reserved if immunomodulators fail or are not tolerated.

Rationale for Immunomodulator First-Line Therapy

This patient has steroid-refractory Crohn's disease, defined as active disease despite adequate prednisolone dosing (>20 mg/day for >2 weeks), which mandates escalation beyond steroids 1.

Azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.25 mg/kg/day) are the first-line agents of choice for steroid-dependent or steroid-refractory disease (Grade A evidence). 1

Why Not 5-ASA (Mesalazine)?

• Mesalazine is ineffective for patients who have needed steroids to induce remission (Grade A evidence). 1
• Mesalazine has limited benefit in Crohn's disease maintenance and is particularly ineffective at doses <2 g/day 1
• While high-dose mesalazine (4 g/daily) may be sufficient for mild ileocolonic disease, this patient has already failed steroids, indicating moderate-to-severe disease 1

Why Not Ileal-Releasing Steroids (Budesonide)?

• Corticosteroids, including budesonide, are not effective for maintenance therapy (Grade A evidence). 1
• Budesonide is appropriate for initial treatment of isolated ileo-caecal disease with moderate activity, but is marginally less effective than prednisolone 1
• This patient has already failed conventional steroids, making additional steroid formulations inappropriate 1
• Long-term steroid treatment is undesirable and does not address the underlying need for disease-modifying therapy 1

When to Escalate to Infliximab

Infliximab (5 mg/kg) should be reserved for patients with moderate-to-severe Crohn's disease who are refractory to or intolerant of steroids, mesalazine, azathioprine/mercaptopurine, and methotrexate, and where surgery is considered inappropriate (Grade A evidence). 1

Infliximab Positioning in Treatment Algorithm:

• Infliximab is effective for steroid-refractory disease (Grade A) but represents second-line therapy after immunomodulators 1
• The standard induction regimen is 5 mg/kg at weeks 0,2, and 6, followed by maintenance every 8 weeks 2, 3, 4
• Combination therapy with azathioprine or mercaptopurine is strongly recommended when initiating infliximab to prevent antibody formation and improve outcomes (Grade A evidence for azathioprine). 3, 5

Alternative: Methotrexate

If azathioprine/mercaptopurine are not tolerated or contraindicated:

• Methotrexate IM 25 mg weekly for up to 16 weeks followed by 15 mg weekly is effective for chronic active disease (Grade A evidence). 1
• Oral dosing is effective for many patients (Grade B) 1
• Folic acid 5 mg once weekly, taken 3 days after methotrexate, may reduce side effects 1

Monitoring Requirements for Azathioprine/Mercaptopurine

• Check FBC within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia 1
• Profound neutropenia and sepsis can develop rapidly despite monitoring 1
• Routine TPMT measurement before treatment is debated but not yet recommended as standard practice 1

Common Pitfalls to Avoid

• Do not continue steroids long-term—they are ineffective for maintenance and carry significant toxicity 1
• Do not add 5-ASA to failed steroid therapy—it lacks efficacy in this setting 1
• Do not use infliximab as first-line therapy—guidelines mandate trial of immunomodulators first unless there are specific contraindications 1
• Do not delay immunomodulation—patients who relapse as steroids are withdrawn require disease-modifying therapy 1

Clinical Decision Algorithm

1. Confirm steroid-refractory status: Active disease despite prednisolone >20 mg/day for >2 weeks 1
2. Initiate azathioprine 1.5-2.5 mg/kg/day (or mercaptopurine 0.75-1.25 mg/kg/day) 1
3. Continue current steroid dose initially while azathioprine takes effect (slow onset of action precludes use as sole therapy) 1
4. Taper steroids gradually once azathioprine effect established (typically 8-12 weeks) 1
5. If azathioprine fails or is not tolerated: Consider methotrexate 1
6. If both immunomodulators fail: Escalate to infliximab with concomitant immunomodulator therapy 1, 3, 5
7. Consider surgery if medical therapy fails and anatomically appropriate 1