What alternative treatment options are available for patients with moderate to severe Inflammatory Bowel Disease (IBD) who cannot tolerate corticosteroids (steroids)?

Alternative Treatments for IBD Patients Who Cannot Tolerate Steroids

For patients with moderate to severe IBD who cannot tolerate corticosteroids, first-line therapy should be azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.5 mg/kg/day), with biologic agents (infliximab, vedolizumab, or ustekinumab) reserved for those who fail or are intolerant of immunomodulators. 1, 2

Treatment Algorithm by Disease Severity

For Mild to Moderate Disease

Ulcerative Colitis:

• Start with high-dose 5-aminosalicylates (mesalazine 4g/day orally) combined with topical mesalazine for distal disease, as this combination is more effective than either alone 3, 4
• For left-sided or extensive disease, oral beclomethasone (topically acting steroid with minimal systemic absorption) can be used as an alternative that avoids systemic steroid side effects 5

Crohn's Disease:

• High-dose mesalazine (4g/daily) may be sufficient for mild ileocolonic disease, though it has limited efficacy compared to its role in UC 1, 4
• Budesonide 9mg daily is appropriate for isolated ileo-cecal disease as it provides topical anti-inflammatory effects with reduced systemic absorption compared to conventional steroids 1
• Elemental or polymeric diets can induce remission in selected patients who have contraindications to steroids or prefer to avoid them 1

For Moderate to Severe Disease or Steroid-Intolerant Patients

First-Line Immunomodulators:

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day are the first-line agents of choice for both steroid-dependent and steroid-intolerant disease 1, 2, 6, 7
• Monitor complete blood count within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia, as profound neutropenia can develop rapidly 1, 2
• These agents have a slow onset of action (typically 8-12 weeks), so they cannot be used as sole therapy for acute flares 1, 8

Second-Line Immunomodulator:

• Methotrexate IM 25mg weekly for up to 16 weeks, then 15mg weekly, is effective for Crohn's disease in patients intolerant of or who have failed azathioprine/mercaptopurine 1, 2
• Add folic acid 5mg once weekly (taken 3 days after methotrexate) to reduce side effects 1, 2
• Important caveat: Methotrexate is NOT effective for ulcerative colitis and should not be used in UC patients 3, 6, 7

Biologic Therapy

When to Use Biologics:

• Reserve biologics for patients with moderate to severe disease who are refractory to or intolerant of steroids, mesalazine, and immunomodulators (azathioprine/mercaptopurine and methotrexate), and where surgery is inappropriate 1, 2, 9

Biologic Options:

• Infliximab 5mg/kg at weeks 0,2, and 6, then every 8 weeks is effective for both UC and CD, including fistulizing Crohn's disease 1, 9, 6
• Vedolizumab (gut-selective integrin antagonist) is effective for moderate to severe UC and CD in patients who have failed conventional therapy 3, 10
• Ustekinumab (IL-12/23 inhibitor) is an alternative biologic option for both UC and CD 3
• For biologic-naive patients, infliximab or vedolizumab are preferred over adalimumab for induction of remission 3

Combination Therapy Considerations:

• Consider combining biologics with azathioprine or mercaptopurine rather than biologic monotherapy for moderate-severe disease, as combination therapy prevents antibody formation and improves outcomes 3, 9
• The American Gastroenterological Association suggests against using thiopurine monotherapy for induction of remission, but supports combination with biologics 3

Critical Pitfalls to Avoid

Monitoring Requirements:

• Do not delay checking complete blood count when starting azathioprine/mercaptopurine—check within 4 weeks and regularly thereafter 1, 2
• Screen for latent tuberculosis before starting infliximab, as serious infections including TB are a major risk 9

Drug-Specific Warnings:

• Never use infliximab doses >5mg/kg in patients with moderate to severe heart failure 9
• Be aware of hepatosplenic T-cell lymphoma risk with TNF blockers, especially in young males with Crohn's disease or UC receiving concomitant azathioprine or 6-mercaptopurine 9
• Methotrexate is ineffective in UC—do not use it for ulcerative colitis patients 3, 6, 7

Surgical Consultation:

• Consider early surgical consultation for patients not responding to medical therapy, as surgery may be more appropriate than escalating to multiple immunosuppressive agents 1
• For UC, surgery should be advised for disease not responding to intensive medical therapy 1
• For CD, surgery should only be undertaken for symptomatic disease and resections should be conservative 1

Special Populations

Fistulizing Crohn's Disease:

• Metronidazole 400mg three times daily and/or ciprofloxacin 500mg twice daily are appropriate first-line treatments for simple perianal fistulae 1
• Infliximab (three infusions of 5mg/kg at weeks 0,2, and 6) should be reserved for refractory fistulae and used as part of a strategy including immunomodulation and surgery 1, 4

Nutritional Support:

• Total parenteral nutrition is appropriate adjunctive therapy in complex, fistulating disease 1
• Elemental or polymeric diets have a role in supporting nutrition while treating active disease 1