What are the treatment options for Inflammatory Bowel Diseases (IBDs)?

Treatment Options for Inflammatory Bowel Disease

For ulcerative colitis, start with combination topical mesalazine 1g daily plus oral mesalazine 2-4g daily, and for Crohn's disease, use high-dose mesalazine 4g daily for mild ileocolonic disease or budesonide 9mg daily for ileocecal disease, escalating to immunomodulators (azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.25mg/kg/day) for steroid-dependent patients, and reserving anti-TNF biologics (infliximab 5mg/kg or adalimumab) for moderate-severe disease refractory to conventional therapy. 1, 2, 3

Ulcerative Colitis Treatment Algorithm

Mild to Moderate Distal UC

• First-line: Combine topical mesalazine 1g daily with oral mesalazine 2-4g daily—this combination is superior to either agent alone 1, 2, 3
• Second-line: Add topical corticosteroids if inadequate response within 2-4 weeks for patients intolerant of topical mesalazine 1, 3
• Topical therapy delivers medication directly to inflamed mucosa, maximizing local effect while minimizing systemic exposure 4, 5

Moderate UC (Failed Combination Mesalazine)

• Oral prednisolone 40mg daily, tapering by 5mg weekly over 8 weeks based on response 1, 3
• Continue oral mesalazine during steroid taper and afterward for maintenance 1
• Critical pitfall: Never use corticosteroids for maintenance therapy—they are ineffective and cause steroid dependency 1, 3

Severe UC (Requires Hospitalization)

• Admit immediately for IV corticosteroids—do not delay for stool cultures 1
• Joint management by gastroenterologist and colorectal surgeon from admission 1, 2
• Monitor vital signs four times daily, daily stool charts, and labs (FBC, CRP, electrolytes, albumin) every 24-48 hours 1
• Daily abdominal radiographs if colonic dilatation >5.5cm detected 1
• IV fluid/electrolyte replacement, transfuse to maintain hemoglobin >10g/dL 1
• Subcutaneous heparin for thromboembolism prophylaxis 1, 2
• Assess response by day 3: Consider rescue therapy with infliximab or ciclosporin for non-responders 1, 2
• Inform patients of 25-30% colectomy risk 1

Maintenance Therapy for UC

• Lifelong aminosalicylate maintenance with mesalazine ≥2g daily for all patients, especially those with left-sided or extensive disease 1, 2
• Maintenance therapy reduces colorectal cancer risk by up to 75% (OR 0.25, CI 0.13 to 0.48) 4
• For steroid-dependent patients: Azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.5mg/kg/day 1, 2

Crohn's Disease Treatment Algorithm

Mild Ileocolonic CD

• High-dose mesalazine 4g daily may suffice as initial therapy 1, 3
• Consider nutritional therapy, antibiotics, or corticosteroids based on disease characteristics 1
• Important limitation: Mesalazine has limited benefit in CD, ineffective at <2g/day or after steroid-induced remission 1

Mild to Moderate Ileocecal CD

• Budesonide 9mg once daily for 8 weeks—as effective as prednisolone with significantly fewer systemic side effects 3, 6
• Budesonide undergoes rapid first-pass hepatic metabolism, reducing systemic exposure while maintaining local efficacy 6

Moderate to Severe CD

• Corticosteroids for induction of remission 1, 2
• Prednisolone 40mg daily tapering by 5mg weekly for colonic disease 3
• Never use corticosteroids for maintenance—they cause steroid dependency and serious adverse events including opportunistic infections, diabetes, hypertension, cataracts, and increased fracture risk 1, 6

Steroid-Dependent or Refractory CD

• Second-line immunomodulation: Azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.25mg/kg/day 4, 1, 2
• Monitor FBC within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia 4
• Alternative: Methotrexate 25mg IM weekly for 16 weeks, then 15mg weekly for chronic active disease or azathioprine intolerance 4, 1, 2
• Add folic acid 5mg weekly (3 days after methotrexate) to reduce side effects 1
• Critical warning: Azathioprine/mercaptopurine carry risk of myelosuppression, hepatotoxicity, and hepatosplenic T-cell lymphoma (particularly in IBD patients, though this is an unapproved use) 7

Moderate-Severe CD Refractory to Conventional Therapy

• Infliximab 5mg/kg at weeks 0,2, and 6 reserved for patients refractory to steroids, mesalazine, and immunomodulators where surgery is inappropriate 4, 1, 2
• Maintenance dosing: 5-10mg/kg every 8 weeks for responders 1
• Use as part of comprehensive strategy including immunomodulation and surgical consultation 1
• Alternative biologic: Adalimumab is FDA-approved for moderately to severely active CD in adults and pediatric patients ≥6 years 8

Perianal/Fistulating CD

• First-line: Metronidazole 400mg TDS and/or ciprofloxacin 500mg BD for simple perianal fistulae 1
• MRI and examination under anesthesia to define anatomy 1
• Azathioprine/mercaptopurine for simple fistulae after excluding distal obstruction and abscess 1
• Infliximab (three infusions at 0,2,6 weeks) for refractory fistulae combined with immunomodulation and surgical drainage 1
• Seton drainage, fistulectomy, or advancement flaps for persistent/complex fistulae 1

Maintenance Therapy for CD

• All smokers must stop—most important factor in maintaining remission 1
• Azathioprine/mercaptopurine effective but reserved as second-line due to toxicity 1
• Methotrexate 15-25mg IM weekly for patients who responded to IM methotrexate induction 1
• Mesalazine >2g/day reduces relapse after surgery (NNT=8), especially after small bowel resection (40% reduction at 18 months) 4

Surgical Management

Indications for Surgery in UC

• Disease not responding to intensive medical therapy 1, 2
• Dysplasia or carcinoma 1, 2
• Poorly controlled disease or recurrent acute-on-chronic episodes 4

Surgical Approach for UC

• Subtotal colectomy with long rectal stump is procedure of choice for acute fulminant disease 1, 2
• Counsel regarding ileo-anal pouch for elective surgery 1, 2

Surgical Principles for CD

• Operate only for symptomatic disease, not asymptomatic radiologic findings 1, 2
• Resections limited to macroscopic disease only—be conservative 4, 1, 2
• Avoid primary anastomosis in presence of sepsis and malnutrition 4, 1
• Consider stricture dilatation or strictureplasty for diffuse small bowel disease 1
• Patients requiring surgery best managed under joint care of surgeon and gastroenterologist with IBD interest 4, 2

Key Monitoring and Safety Considerations

Aminosalicylate Safety

• 5-ASA safety profile comparable to placebo and superior to sulfasalazine 6
• Rare nephrotoxicity (interstitial nephritis) reported—assess renal function before and during treatment 6
• Mesalazine tolerated by 80% of those unable to tolerate sulfasalazine 4

Immunomodulator Monitoring

• FBC monitoring for azathioprine/mercaptopurine: within 4 weeks of starting, then every 6-12 weeks 4
• Liver function tests weekly when starting, then monthly 7
• Consider TPMT or NUDT15 testing for patients with severe myelosuppression 7
• Reduce azathioprine dose by 75% when coadministered with allopurinol 7

Biologic Therapy Considerations

• Anti-TNF agents increase risk of opportunistic infections and malignancies 8, 7
• Screen for tuberculosis before initiating anti-TNF therapy 8
• Effectiveness not established in patients who lost response to or were intolerant of TNF blockers 8