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

Treatment Options for Inflammatory Bowel Disease

For ulcerative colitis, start with aminosalicylates (mesalazine 4g daily) for mild-to-moderate disease, escalating to corticosteroids (prednisolone 40mg daily) for moderate-to-severe disease or inadequate response, with immunomodulators (azathioprine/mercaptopurine) for steroid-dependent disease and biologics (infliximab) reserved for refractory cases; for Crohn's disease, use corticosteroids or budesonide 9mg daily for moderate disease, with early immunomodulator or biologic therapy for patients with poor prognostic factors. 1, 2, 3

Ulcerative Colitis Treatment Algorithm

Mild-to-Moderate Disease

• Aminosalicylates are first-line therapy for inducing and maintaining remission in ulcerative colitis 1, 2, 3
• Topical mesalazine or corticosteroids provide prompt symptom relief for distal disease 1
• High-dose oral mesalazine (4g daily) is appropriate for more extensive disease 1

Moderate-to-Severe Disease

• Oral prednisolone 40mg daily should be initiated for patients failing aminosalicylates or presenting with moderate-to-severe symptoms 1, 3
• Taper prednisolone gradually over 8 weeks to prevent early relapse; more rapid reduction increases relapse risk 1, 3
• Avoid using corticosteroids for maintenance therapy as they are ineffective and carry significant adverse effects 1

Severe/Fulminant Disease

• Admit for intensive intravenous therapy patients meeting Truelove and Witts' criteria or failing maximal oral treatment 1
• Monitor pulse rate, stool frequency, C-reactive protein, and plain abdominal radiography daily to identify patients requiring colectomy 1
• Provide intravenous fluid/electrolyte replacement, blood transfusion to maintain hemoglobin >10 g/dl, and subcutaneous heparin for thromboembolism prophylaxis 1
• Joint medical-surgical management is essential with close liaison between gastroenterologist and colorectal surgeon 1, 2

Maintenance Therapy

• Lifelong maintenance therapy with aminosalicylates is recommended for all patients, especially those with left-sided or extensive disease 1, 2
• Discontinuation may be reasonable only for distal disease patients in remission for 2 years who are averse to medication 1

Crohn's Disease Treatment Algorithm

Mild-to-Moderate Disease

• High-dose mesalazine (4g daily) may be sufficient for mild ileocolonic Crohn's disease, though less effective than in ulcerative colitis 1, 2, 3
• Budesonide 9mg daily is appropriate for isolated ileo-caecal disease with moderate activity, though marginally less effective than prednisolone 1, 3
• Prednisolone 40mg daily for moderate-to-severe disease or mild-to-moderate disease unresponsive to mesalazine, tapered over 8 weeks 1, 3

Steroid-Dependent or Refractory Disease

• Immunomodulators (azathioprine 2-2.5mg/kg or mercaptopurine 1-1.5mg/kg) should be initiated for chronic active steroid-dependent disease 1, 2
• Monitor full blood count within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia 1, 4
• Methotrexate 25mg IM weekly for 16 weeks, then 15mg weekly is effective for chronic active disease; oral dosing works for many patients 1

Moderate-to-Severe Refractory Disease

• Infliximab 5mg/kg should be reserved for patients refractory to or intolerant of steroids, mesalazine, azathioprine/mercaptopurine, and methotrexate, where surgery is inappropriate 1, 5
• Infliximab is indicated for reducing signs/symptoms, inducing/maintaining clinical remission, and reducing draining fistulas in fistulizing disease 5

Management of Persistent Symptoms in Quiescent IBD

Diagnostic Approach

• Follow a stepwise approach to rule out ongoing inflammation using fecal calprotectin measurement, endoscopy with biopsy, and cross-sectional imaging 1, 2
• Consider anatomic abnormalities or structural complications in patients with obstructive symptoms (distention, pain, nausea, vomiting, constipation) 1, 2
• Evaluate alternative mechanisms including small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, and chronic pancreatitis based on symptom patterns 1, 2

Symptom-Specific Management

For chronic diarrhea:

• Hypomotility agents or bile-acid sequestrants may be used in quiescent IBD 1, 2, 3

For chronic constipation:

• Osmotic and stimulant laxatives should be offered 1, 2, 3

For functional pain:

• Use antispasmodics, neuropathic-directed agents, and antidepressants while avoiding opiates 1, 2, 3
• Opiates should be avoided due to risk of worsening underlying disease and dependence 1

Adjunctive Therapies

Dietary Interventions

• A low FODMAP diet may be offered for functional GI symptoms with careful attention to nutritional adequacy 1, 2, 3

Psychological Therapies

• Cognitive behavioral therapy, hypnotherapy, and mindfulness therapy should be considered for IBD patients with functional symptoms 1, 2, 3

Other Supportive Measures

• Probiotics may be considered for functional symptoms, though evidence is limited 1, 2, 3
• Physical exercise should be encouraged in all IBD patients with functional symptoms 1, 2, 3
• Pelvic floor therapy should be offered to patients with defecatory disorders 1
• Fecal microbiota transplant should not be offered for functional symptoms until further evidence is available 1

Surgical Considerations

Ulcerative Colitis

• Surgery is indicated for disease not responding to intensive medical therapy, dysplasia/carcinoma, or poorly controlled disease 1, 2, 3
• Decisions should be made jointly by gastroenterologist and colorectal surgeon in consultation with the patient 1, 2
• Patients should be informed of a 25-30% chance of needing colectomy 1

Crohn's Disease

• Surgery should only be undertaken for symptomatic disease, not asymptomatic radiologically-identified disease, as it is potentially panenteric and usually recurs 1, 2, 3
• Resections should be conservative and limited to macroscopic disease 1, 3

Critical Pitfalls to Avoid

• Do not overprescribe mesalamine for Crohn's disease where it has limited efficacy compared to ulcerative colitis 6
• Avoid inappropriate steroid use for perianal disease, in presence of sepsis, or for maintenance therapy 6
• Do not delay introduction or underdose immunomodulators (azathioprine/mercaptopurine/methotrexate) in steroid-dependent patients 6
• Avoid introducing anti-TNF therapy too late in disease progression, but also avoid using it inappropriately when sepsis or fibrostenotic strictures are present 6
• Do not overtreat inflammation for symptoms due to functional pathophysiology, as this increases adverse effects without symptomatic benefit 1
• Monitor for hepatotoxicity with immunomodulators through regular liver function tests, especially when combined with other hepatotoxic drugs 1, 4
• Be aware of malignancy risk, particularly hepatosplenic T-cell lymphoma with mercaptopurine in IBD (though this is an unapproved use) 4