What are the initial and subsequent treatment options for inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease?

High-Yield Notes on IBD Treatment (Harrison's Chapter 326)

Initial Treatment of Ulcerative Colitis

Mild to Moderate Active Disease

For mild to moderate ulcerative colitis, start with high-dose oral aminosalicylates at 4-4.8 g daily of the active 5-ASA moiety, rather than starting low and escalating. 1, 2

Left-Sided or Extensive Disease

• Combination therapy with oral mesalazine 2-4 g daily PLUS topical mesalazine 1 g daily is superior to either agent alone 1
• Oral options include: mesalazine 2-4 g daily, olsalazine 1.5-3 g daily, or balsalazide 6.75 g daily 1
• Topical formulation selection depends on disease extent: suppositories for disease to recto-sigmoid junction, foam or liquid enemas for more proximal disease 1
• Topical corticosteroids are less effective than topical mesalazine and should be reserved as second-line therapy 1

Distal Colitis (Proctitis)

• First-line: topical mesalazine 1 g daily combined with oral mesalazine 2-4 g daily 1
• Combination therapy is more effective than either topical or oral mesalazine alone 1
• Address proximal constipation with stool bulking agents or laxatives to improve drug retention 1

Moderate to Severe Active Disease

When aminosalicylates fail or prompt response is required, initiate prednisolone 40 mg daily 1, 3

• Taper prednisolone gradually over 8 weeks according to severity and patient response—more rapid reduction is associated with early relapse 1, 4
• Long-term corticosteroid use is undesirable and should be avoided 1
• For isolated ileo-caecal disease with moderate activity, budesonide 9 mg daily is an alternative, though marginally less effective than prednisolone 1, 3

Severe/Fulminant Ulcerative Colitis

Patients meeting Truelove and Witts' criteria for severe disease require hospital admission for intensive intravenous therapy 1

• Intravenous steroids: hydrocortisone 400 mg/day or methylprednisolone 60 mg/day 3
• Monitor pulse rate, stool frequency, C-reactive protein, and plain abdominal radiograph to identify patients needing colectomy 1
• For corticosteroid-refractory severe UC, ciclosporin may be effective as rescue therapy 1
• JAK inhibitors in acute severe UC should be restricted to corticosteroid-refractory patients in whom conventional rescue therapy is contraindicated or has historically failed, pending further RCT evidence 1

Initial Treatment of Crohn's Disease

Mild to Moderate Ileocolonic Disease

High-dose mesalazine 4 g daily is appropriate first-line therapy for mild ileal or ileocolonic Crohn's disease 3, 4

• For less severe symptoms with ileocaecal location, ileal-release budesonide may be tried initially 1
• If budesonide is ineffective, prednisolone is required 1

Moderate to Severe Disease

Systemic corticosteroids remain effective initial therapy for moderate to severely active Crohn's disease, regardless of location 1

• Prednisolone 40 mg daily for patients requiring prompt response or those failing mesalazine 1, 3
• Taper over 8 weeks to prevent early relapse 1, 4
• For teenagers with incomplete growth or patients with diabetes/steroid intolerance, consider alternatives including exclusive enteral nutrition (EEN) 1

High-Risk or Aggressive Disease

In patients with aggressive disease course or poor prognostic factors, consider early introduction of biologics 1

High-risk features include: 1

• Complex (stricturing or penetrating) disease at presentation
• Perianal fistulizing disease
• Age under 40 years at diagnosis
• Need for steroids to control index flare

Anti-TNF therapy, vedolizumab, and ustekinumab can all be considered as first-line biologics 1

Localized Ileocaecal Disease

Laparoscopic ileocaecal resection should be considered as an alternative to medical therapy in patients failing or relapsing after initial treatment, or those preferring surgery 1

• The LIR!C study demonstrated equivalence between laparoscopic resection and infliximab across multiple comparators 1
• Approximately 39% of infliximab patients required surgery during median 4-year follow-up, while 26% of surgery patients required infliximab 1

Maintenance Therapy

Ulcerative Colitis Maintenance

For chronic active steroid-dependent UC, use azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day as steroid-sparing agents 1, 3

• Topical agents (steroids or mesalazine) may be added as adjunctive therapy for troublesome rectal symptoms 1
• Corticosteroids are NOT effective for maintaining remission and should not be used long-term 1

Crohn's Disease Maintenance

Corticosteroids are not effective in maintaining remission in Crohn's disease 1

• Budesonide does not reduce relapse rates over 12 months and causes more adverse events than placebo 1
• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day for steroid-dependent disease 1, 3

Special Situations

Pouchitis (Post-IPAA Surgery)

First-line therapy: metronidazole 400 mg three times daily or ciprofloxacin 250 mg twice daily for 2 weeks 1

• Up to 45% of patients undergoing ileal pouch surgery for UC develop pouchitis 1
• If antibiotics are ineffective, mesalazine or corticosteroids may be used 1
• For chronic pouchitis: long-term low-dose metronidazole or ciprofloxacin 1
• VSL3 probiotic therapy may be used for chronic pouchitis 1

Nutritional Support in Crohn's Disease

Nutrition should be considered an integral component of management for all Crohn's disease patients 1

• Nutritional support is disease-modifying therapy for growth failure in children/adolescents with active small bowel disease 1
• May be used in preference to steroids, immunomodulators, or surgery after detailed discussion 1
• Appropriate for malnourished patients, those with intestinal partial obstruction awaiting surgery, or severe perianal disease 1
• Monitor vitamin B12 status, especially after ileal resection 1

Pregnancy Management

Maintaining adequate disease control during pregnancy is essential for both maternal and fetal health 1

• Approximately 25% of female IBD patients conceive after diagnosis 1
• Disease activity control takes priority over theoretical medication risks 1

Preoperative Medication Management

Prior to elective surgery for UC, corticosteroids should be stopped or dose minimized to reduce postoperative complications 1

• Anti-TNF therapy can be continued in the preoperative period 1
• Anti-integrin therapy (vedolizumab) can be continued preoperatively 1
• 5-ASAs and purine analogues are not associated with increased postoperative complications 1

Surveillance for Colorectal Cancer

Colonoscopy after 8-10 years to re-evaluate disease extent is advisable 1

For extensive colitis opting for surveillance: 1

• Every 3 years in second decade of disease
• Every 2 years in third decade
• Annually in fourth decade

Patients with primary sclerosing cholangitis require more frequent (perhaps annual) colonoscopy due to higher cancer risk 1

• Four random biopsies every 10 cm from entire colon plus additional samples of suspicious areas 1
• If dysplasia (any grade) is confirmed by second GI pathologist, colectomy is usually advisable 1

Common Pitfalls and Caveats

Aminosalicylate Dosing

• Do not start at low doses and escalate—begin with 4-4.8 g daily for optimal efficacy 1, 2
• Sulfasalazine has higher incidence of side effects compared to newer 5-ASA drugs; reserve for selected patients (e.g., reactive arthropathy) 1

Corticosteroid Management

• Avoid rapid tapering—associated with early relapse 1, 4
• Never use corticosteroids for long-term maintenance therapy 1
• Patients should not undergo pouch surgery while taking corticosteroids 1

Biologic Therapy Considerations

• Ustekinumab pharmacokinetics are similar between Crohn's disease and ulcerative colitis patients 5
• Approximately 2.9-4.6% of patients develop antibodies to ustekinumab during one year of treatment 5
• Concomitant immunomodulators (6-MP, AZA, MTX) or corticosteroids do not appear to influence ustekinumab safety or efficacy 5

Disease-Specific Considerations

• In Crohn's disease, always consider alternative explanations for symptoms beyond active inflammation: bacterial overgrowth, bile salt malabsorption, fibrotic strictures 4
• Metronidazole 10-20 mg/kg/day can be effective in Crohn's disease but is not usually recommended as first-line due to side effects 4