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

Treatment Options for Inflammatory Bowel Disease

For mild to moderate ulcerative colitis, start with topical and oral aminosalicylates (mesalazine 4g daily), escalating to corticosteroids (prednisolone 40mg daily tapered over 8 weeks) if inadequate response, while for Crohn's disease, proceed directly to corticosteroids for moderate-severe disease or consider high-dose mesalazine only for mild ileocolonic disease. 1, 2, 3, 4

Algorithmic Approach to IBD Treatment

Step 1: Disease Assessment and Severity Stratification

Before initiating therapy, determine disease type (ulcerative colitis vs. Crohn's disease), location (ileal, ileocolonic, colonic), pattern (inflammatory, stricturing, fistulating), and activity level. 1 A critical pitfall is treating symptoms without first ruling out active inflammation—use fecal calprotectin, endoscopy with biopsy, and cross-sectional imaging to confirm inflammatory activity versus functional symptoms. 1, 2

Step 2: First-Line Therapy Selection

For Ulcerative Colitis:

• Distal/mild disease: Topical mesalazine combined with oral mesalazine (4g daily) provides optimal first-line therapy. 4 Add topical corticosteroids if mesalazine alone is insufficient. 1, 4

• Moderate-severe disease: Oral prednisolone 40mg daily, tapered gradually over 8 weeks (rapid tapering causes early relapse). 1, 3, 4

• Severe disease (Truelove-Witts criteria): Immediate hospitalization for intravenous corticosteroids with joint gastroenterology-surgical management. 1, 4 Monitor pulse, stool frequency, C-reactive protein, and abdominal radiographs daily. 1 If no response by day 3, initiate rescue therapy with infliximab or ciclosporin. 4

For Crohn's Disease:

• Mild ileocolonic disease: High-dose mesalazine (4g daily) may suffice, though evidence is weaker than for ulcerative colitis. 1, 2, 3

• Moderate-severe disease: Prednisolone 40mg daily tapered over 8 weeks is the appropriate initial therapy. 1, 3 For isolated ileocecal disease, budesonide 9mg daily is marginally less effective but has fewer systemic side effects. 1

Step 3: Maintenance and Steroid-Sparing Strategies

Lifelong maintenance therapy is recommended for all ulcerative colitis patients, especially those with left-sided or extensive disease, as it reduces relapse risk and colorectal cancer incidence. 1, 4

Immunomodulators for steroid-dependent disease:

• Azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.25 mg/kg/day) should be initiated for patients requiring repeated steroid courses. 2, 4, 5 Critical monitoring requirement: Check full blood count regularly to detect neutropenia, and consider TPMT/NUDT15 genotyping before initiation to identify patients requiring dose reduction. 5

• Methotrexate 25mg IM weekly for 16 weeks, then 15mg weekly is effective for chronic active Crohn's disease. 4

Step 4: Biologic Therapy

Infliximab is FDA-approved for moderate to severe Crohn's disease and ulcerative colitis with inadequate response to conventional therapy, and for fistulizing Crohn's disease. 6 Reserve biologics for patients refractory to or intolerant of steroids, mesalazine, and immunomodulators when surgery is inappropriate. 3, 4 Other options include adalimumab, ustekinumab, vedolizumab, and JAK inhibitors like tofacitinib. 3

Step 5: Surgical Intervention

Surgery should be considered when medical therapy fails or complications develop (strictures, fistulas, abscesses). 4

• Ulcerative colitis: Subtotal colectomy is the procedure of choice for acute fulminant disease not responding to intensive medical therapy. 1, 4 Patients have a 25-30% chance of requiring colectomy. 1

• Crohn's disease: Surgery should only be considered when symptomatic, as disease typically recurs. 2, 3 Resections must be conservative and limited to macroscopic disease. 3, 4

Management of Functional Symptoms in Quiescent IBD

A common pitfall is escalating immunosuppression for symptoms caused by functional pathophysiology rather than active inflammation—this increases adverse effects without symptomatic benefit. 1

For persistent symptoms with confirmed quiescent disease:

• Chronic diarrhea: Loperamide, bile acid sequestrants, or hypomotility agents. 1, 2, 3

• Chronic constipation: Osmotic laxatives (polyethylene glycol) and stimulant laxatives. 1, 2, 3

• Functional pain: Antispasmodics, tricyclic antidepressants, or neuropathic agents—avoid opiates. 1, 2, 3

• Dietary intervention: Low FODMAP diet with careful nutritional monitoring. 1, 2, 3

• Psychological therapies: Cognitive behavioral therapy, hypnotherapy, or mindfulness therapy. 1, 2, 3

• Probiotics: May be considered with low risk of harm. 1, 2, 3

• Physical exercise: Should be encouraged as it decreases risk of active disease in remission. 2, 3

Critical Drug Interactions and Precautions

When coadministering allopurinol with azathioprine or mercaptopurine, reduce the thiopurine dose by 50-75% to prevent severe myelosuppression. 5 Aminosalicylates also potentiate myelosuppression. 5

Mercaptopurine carries significant hepatotoxicity risk—monitor serum transaminases, alkaline phosphatase, and bilirubin weekly initially, then monthly. 5 Hepatosplenic T-cell lymphoma has been reported with mercaptopurine use in IBD (though this is an unapproved indication). 5

Venous thromboembolism prophylaxis with low molecular weight heparin is essential for all hospitalized IBD patients due to elevated thrombotic risk. 4

Emerging Treatment Paradigms

Recent evidence supports a shift from traditional step-up therapy to accelerated step-up or top-down approaches in selected patients with poor prognostic factors. 7 The therapeutic target has evolved from clinical remission to objective parameters like endoscopic healing, as symptoms poorly correlate with inflammatory activity and intestinal damage. 7 Tight monitoring with non-invasive biomarkers (C-reactive protein, fecal calprotectin) and therapeutic drug monitoring improves clinical and endoscopic outcomes. 7