What is the treatment approach for inflammatory bowel disease (IBD)?

Treatment Approach for Inflammatory Bowel Disease (IBD)

The treatment of inflammatory bowel disease follows a step-up approach, beginning with mesalamine for mild to moderate disease, progressing to corticosteroids for inadequate response, and advancing to immunomodulators and biologics for refractory cases, with surgery reserved for specific complications or treatment failures. 1

Diagnosis and Assessment

• IBD encompasses primarily ulcerative colitis (UC) and Crohn's disease (CD)
• UC shows mucosal inflammation starting in the rectum with proximal progression
• CD involves transmural inflammation that can affect any part of the GI tract, commonly the terminal ileum and colon 2
• Diagnostic workup should include:
  • Complete blood count
  • Inflammatory markers (CRP or ESR)
  • Electrolytes and liver function tests
  • Stool samples for culture and C. difficile toxin assay 1
• Fecal calprotectin >150 mg/g indicates active inflammation 1

Treatment Algorithm

First-Line Therapy

• For mild to moderate UC:

  • Standard dose oral mesalamine (2-3 g/day) for extensive or left-sided disease 1
  • Mesalamine enemas or suppositories for proctosigmoiditis or proctitis 1
  • Optimization strategies:
    • Combine oral and rectal mesalamine for better response
    • Consider once-daily dosing for improved adherence
    • Increase to high-dose mesalamine (>3 g/day) for suboptimal response 1

• For mild to moderate CD:

  • Conventional immunosuppressive therapies including:
    • Azathioprine
    • 6-mercaptopurine
    • Methotrexate 2

Treatment Escalation

• For inadequate response to first-line therapy:

  • Add oral prednisone or budesonide MMX to optimized 5-ASA therapy 1
  • Corticosteroids (40-60 mg daily) for severe disease 1
  • Monitor for adverse effects:
    • Short-term: acne, edema, sleep disturbances, mood changes
    • Long-term: osteoporosis, adrenal suppression, increased infection risk 1

• For steroid-dependent or steroid-refractory disease:

  • Azathioprine or mercaptopurine as steroid-sparing agents 1
  • Biologics:
    • Anti-TNF agents (infliximab, adalimumab, golimumab) - typically first biologic due to effectiveness/safety profile and lower costs with biosimilars 2
    • Infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks 1, 3
    • Vedolizumab (anti-integrin) for preventing leukocyte homing to the gut 2, 1
    • Ustekinumab for CD (blocks IL-12/23 pathway) 2
  • Small molecules:
    • Tofacitinib (JAK inhibitor) for UC 2

Surgical Management

• Indications for surgery:

  • Disease not responding to intensive medical therapy
  • Complications (free perforation, massive hemorrhage, toxic megacolon)
  • Dysplasia or carcinoma
  • Clinical deterioration despite appropriate medical management 1

• Surgical principles:

  • Subtotal colectomy with ileostomy for severe UC
  • Preservation of maximum intestinal length
  • Limit resection to macroscopically affected segments
  • Avoid primary anastomosis in presence of sepsis or malnutrition 1

Disease-Specific Considerations

Ulcerative Colitis

• Treatment based on disease extent and severity:
  • Proctitis: Mesalamine suppositories; rectal corticosteroids for those intolerant or refractory 1
  • Left-sided or extensive disease: Oral mesalamine with rectal therapy 1
  • Severe disease: Corticosteroids, consider early rescue therapy (infliximab, cyclosporine) if no improvement within 3-5 days 1

Crohn's Disease

• Treatment based on disease phenotype and location:
  • Inflammatory phenotype: Immunosuppressives and biologics
  • Stricturing disease: Consider surgery for symptomatic strictures
  • Fistulizing disease: Anti-TNF therapy (particularly infliximab) shows efficacy 3
  • In clinical trials, infliximab demonstrated:
    • 68% response rate for fistulizing CD at 5 mg/kg
    • 52% complete fistula closure vs. 13% with placebo 3

Supportive Care

• Joint management by gastroenterologist and colorectal surgeon for hospitalized patients 1
• Daily monitoring of vital signs, abdominal examination, and stool frequency/character 1
• Intravenous fluid resuscitation and electrolyte replacement 1
• Venous thromboembolism prophylaxis (essential due to high thrombotic risk) 1
• NPO status if severe symptoms or risk of perforation 1

Monitoring Treatment Response

• Assess clinical response within 3-7 days of initiating therapy 1
• Monitor stool frequency, bleeding, abdominal pain, and vital signs 1
• Check laboratory markers (WBC, CRP, albumin) 1
• Perform endoscopic assessment after 4-8 weeks to confirm mucosal healing 1

Common Pitfalls and Caveats

• Failure to test for C. difficile infection before starting immunosuppressive therapy can lead to inappropriate treatment 1
• Inadequate initial resuscitation can lead to complications; ensure proper fluid and electrolyte replacement 1
• Overlooking VTE prophylaxis increases thrombotic risk in colitis patients 1
• Delayed escalation of therapy in non-responders can lead to disease progression and complications
• Poor medication adherence, particularly with mesalamine, is common and can lead to suboptimal outcomes 4

The management of IBD has improved significantly in recent decades, with surgery rates decreasing from 44% to 21% after 10 years of disease for CD and 5-year colectomy rates of 4.1% for UC 2. This improvement is attributed to the introduction of biologics and improved multidisciplinary IBD management.