What are the treatment options for inflammatory bowel disease (IBD)?

Treatment Options for Inflammatory Bowel Disease

The treatment of IBD follows a stepwise approach starting with aminosalicylates for mild-to-moderate ulcerative colitis, corticosteroids for moderate-to-severe disease or Crohn's disease, followed by immunomodulators (azathioprine/mercaptopurine) for steroid-dependent disease, and biologics (infliximab) reserved for refractory cases or when surgery is inappropriate. 1, 2

Initial Assessment and Disease Stratification

Before initiating therapy, rule out ongoing inflammatory activity using fecal calprotectin measurement, endoscopy with biopsy, and cross-sectional imaging in patients with persistent GI symptoms. 1, 3 Consider anatomic abnormalities or structural complications in patients presenting with obstructive symptoms including abdominal distention, pain, nausea, vomiting, or constipation. 1, 3

First-Line Therapies

For Ulcerative Colitis

• Aminosalicylates (mesalazine 4g daily) are effective for inducing and maintaining remission in mild-to-moderate ulcerative colitis, with topical formulations providing additional benefit for distal disease. 1, 2
• Topical mesalazine or corticosteroids should be used for distal disease to give prompt symptom relief. 1
• Lifelong maintenance therapy is generally recommended for all patients, especially those with left-sided or extensive disease. 1

For Crohn's Disease

• High-dose mesalazine (4g daily) may be sufficient for mild ileocolonic Crohn's disease, though it is less effective than in ulcerative colitis. 1, 2
• Prednisolone 40mg daily is appropriate for moderate-to-severe disease or mild-to-moderate ileocolonic disease that failed mesalazine, tapered gradually over 8 weeks to avoid early relapse. 1, 2
• Budesonide 9mg daily is appropriate for isolated ileo-caecal disease with moderate activity, though marginally less effective than prednisolone. 1

Second-Line Therapies: Immunomodulators

Azathioprine or mercaptopurine should be initiated for chronic active steroid-dependent disease when steroids cannot be withdrawn without deterioration. 1, 2 Monitor full blood count within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia. 1, 4 The FDA label warns that myelosuppression is the most consistent dose-related adverse reaction, and patients with TPMT or NUDT15 deficiency may require dose reduction. 4

Methotrexate IM 25mg weekly for up to 16 weeks followed by 15mg weekly is effective for chronic active Crohn's disease, with oral dosing effective for many patients. 1

Third-Line Therapies: Biologics

Infliximab (5mg/kg) should be reserved for patients with moderate-to-severe Crohn's disease or ulcerative colitis who are refractory to or intolerant of steroids, mesalazine, azathioprine/mercaptopurine, and methotrexate, and where surgery is considered inappropriate. 1, 2, 5 The FDA label indicates infliximab is approved for reducing signs and symptoms, inducing and maintaining clinical remission in adult patients with moderately to severely active disease who have had inadequate response to conventional therapy. 5

Other biologics including ustekinumab, vedolizumab, and JAK inhibitors like tofacitinib are also effective for Crohn's disease treatment. 2

Severe Disease Management

Severe Ulcerative Colitis

Patients who fail maximal oral treatment or present with severe disease by Truelove and Witts' criteria require hospital admission for intensive intravenous therapy with joint medical and surgical management. 1 Monitor pulse rate, stool frequency, C-reactive protein, and plain abdominal radiograph to identify those needing colectomy. 1 Provide:

• Intravenous fluid and electrolyte replacement with blood transfusion to maintain hemoglobin >10 g/dl. 1
• Subcutaneous heparin to reduce thromboembolism risk. 1
• Nutritional support if malnourished. 1
• Patients should be informed of a 25-30% chance of needing colectomy. 1

Symptom-Specific Management

For Diarrhea

• Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. 1, 2

For Constipation

• Osmotic and stimulant laxatives should be offered to IBD patients with chronic constipation. 1, 3

For Pain

• Antispasmodics, neuropathic-directed agents, and antidepressants should be used for functional pain in IBD, while opiates should be avoided. 1, 3

Adjunctive Therapies

• A low FODMAP diet may be offered for functional GI symptoms with careful attention to nutritional adequacy. 1, 2
• Psychological therapies (cognitive behavioral therapy, hypnotherapy, mindfulness therapy) should be considered for IBD patients with functional symptoms. 1, 2
• Probiotics may be considered for functional symptoms, though further research is needed. 1, 2
• Physical exercise should be encouraged in all IBD patients. 1, 3
• Pelvic floor therapy should be offered to patients with evidence of defecatory disorder. 1

Surgical Considerations

For Ulcerative Colitis

Surgery should be advised for disease not responding to intensive medical therapy, with decisions made jointly by gastroenterologist and colorectal surgeon in consultation with the patient. 1, 2, 3 Patients requiring elective surgery should be counseled regarding all surgical options, including ileo-anal pouch where appropriate. 1

For Crohn's Disease

Surgery should only be undertaken for symptomatic rather than asymptomatic disease, as it is potentially panenteric and usually recurs following surgery. 1, 2, 3 Resections should be conservative and limited to macroscopic disease. 1, 2

Critical Pitfalls to Avoid

• Do not overtreat intestinal inflammation for symptoms due to functional pathophysiology, as this increases risk of adverse effects without symptomatic benefit. 1
• Do not use opiates for chronic pain management in IBD due to risks of dependence and complications. 1
• Do not delay introduction of immunomodulators in steroid-dependent disease. 6
• Do not use fecal microbiota transplant for functional GI symptoms in IBD until further evidence is available. 1
• Do not routinely offer complementary and alternative therapies for functional symptoms until further evidence is available. 1
• The FDA warns that hepatosplenic T-cell lymphoma has been reported in patients treated with mercaptopurine for IBD, though this is an unapproved use. 4