What are the treatment options for Inflammatory Bowel Disease (IBD)?

Treatment Options for Inflammatory Bowel Disease

For ulcerative colitis, start with combination topical mesalazine 1g daily plus oral mesalazine 2-4g daily as first-line therapy; for Crohn's disease, initiate high-dose mesalazine 4g daily for mild disease or corticosteroids for moderate-severe disease, escalating to immunomodulators (azathioprine/mercaptopurine) for steroid-dependent patients and reserving infliximab for refractory cases. 1, 2

Ulcerative Colitis Treatment Algorithm

Mild to Moderate Distal Disease

• Combination therapy is superior to monotherapy: topical mesalazine 1g daily PLUS oral mesalazine 2-4g daily provides optimal efficacy 1, 2, 3
• Topical corticosteroids serve as second-line for patients who cannot tolerate topical mesalazine 1
• The combination approach outperforms either agent alone in achieving remission 1

Moderate Extensive Disease

• Oral prednisolone 40mg daily when combination mesalazine fails 1, 3
• Taper gradually over 8 weeks based on clinical response 1
• Critical pitfall: Never use corticosteroids for maintenance—they are ineffective and cause steroid dependency 4

Severe Disease (Medical Emergency)

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

Maintenance Therapy

• Lifelong aminosalicylate maintenance with mesalazine ≥2g daily for all patients, especially those with left-sided or extensive disease 1, 2, 3
• This reduces colorectal cancer risk by up to 75% 4
• Azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.5mg/kg/day for steroid-dependent patients 1, 2, 3
• Monitor FBC within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia 4

Crohn's Disease Treatment Algorithm

Mild Ileocolonic Disease

• High-dose mesalazine 4g daily may suffice as initial therapy 1, 2
• 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

Moderate to Severe Disease

• Corticosteroids for induction of remission 1, 2
• Budesonide for ileal/right-sided colonic disease with lower systemic effects 1
• Never use corticosteroids for maintenance—they cause steroid dependency without preventing relapse 1

Steroid-Dependent or Refractory Disease

• Azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.25mg/kg/day as second-line immunomodulation 4, 1, 2
• 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
• Infliximab 5mg/kg at weeks 0,2, and 6 reserved for moderate-severe CD refractory to steroids, mesalazine, and immunomodulators where surgery is inappropriate 4, 1, 2
• Maintenance dosing: 5-10mg/kg every 8 weeks for responders 1
• Adalimumab is FDA-approved for moderately to severely active Crohn's disease 5

Perianal/Fistulating Disease

• 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

• All smokers must stop—most important factor in maintaining remission in CD 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 4

Surgical Management

Ulcerative Colitis

• Surgery indicated for disease not responding to intensive medical therapy, dysplasia, or carcinoma 4, 1, 2, 3
• Subtotal colectomy with long rectal stump is procedure of choice for acute fulminant disease 4, 1, 2, 3
• Counsel regarding ileo-anal pouch for elective surgery 4, 1

Crohn's Disease

• Operate only for symptomatic disease, not asymptomatic radiologic findings—CD is potentially panenteric and usually recurs 4, 1
• Resections limited to macroscopic disease only—be conservative 4, 1, 2, 3
• Avoid primary anastomosis in presence of sepsis and malnutrition 4, 1
• Consider stricture dilatation or strictureplasty for diffuse small bowel disease 1

Critical Safety Considerations

Monitoring Requirements

• Azathioprine/mercaptopurine: FBC within 4 weeks, then every 6-12 weeks to detect neutropenia 4
• Consider TPMT or NUDT15 testing for patients with severe myelosuppression 6
• Monitor liver tests weekly initially, then monthly for hepatotoxicity 6
• Reduce azathioprine dose by 75% when coadministered with allopurinol 6

Serious Adverse Events

• Hepatosplenic T-cell lymphoma reported with mercaptopurine in IBD patients (though IBD is an unapproved use) 6
• Corticosteroids cause opportunistic infections, diabetes, hypertension, glaucoma, cataracts, psychiatric complications, and increased fracture risk, particularly with high doses and prolonged treatment 7
• Mesalazine nephrotoxicity (interstitial nephritis) is rare but requires renal function assessment before and during treatment 7
• All hospitalized IBD patients require LMWH for thromboembolism prophylaxis due to exceptionally high thrombotic risk 1, 3

Pregnancy Considerations

• Mercaptopurine can cause fetal harm with increased miscarriage risk in first trimester 6
• Females of reproductive potential should use effective contraception during treatment and for 6 months after last dose 6
• Males with female partners should use contraception during treatment and for 3 months after last dose 6
• Mesalazine is considered safe in pregnancy, excluding formulations with dibutyl phthalate 8

Organizational Structure for Optimal Care

• Establish multidisciplinary team including gastroenterologists, colorectal surgeons, dieticians, and psychological support 3
• Provide rapid access to clinic appointments for new symptoms and disease relapses 3
• Direct telephone access to care team for urgent concerns 3
• Continuity of care with same clinician whenever possible 3