What is the treatment approach for Crohn's Disease, including management of disease flares and scoring tools to define severity?

Treatment of Crohn's Disease and Severity Scoring

Severity Assessment

The Crohn's Disease Activity Index (CDAI) score of 220 or higher defines moderate to severe disease, which guides treatment decisions based on structural damage, inflammatory burden, and quality of life impact 1.

Treatment Approach by Disease Severity

Mild Disease (CDAI < 220)

For mild ileocecal Crohn's disease, start with oral budesonide 9 mg/day as first-line therapy to induce remission 1.

• Evaluate symptomatic response to budesonide between 4-8 weeks to determine if therapy modification is needed 1.
• For mild disease limited to the colon, sulfasalazine can be considered, with response evaluation at 2-4 months 1, 2.
• Avoid 5-aminosalicylate (5-ASA) agents for induction or maintenance of remission—they are ineffective 1.
• Budesonide should not be used for maintenance therapy due to lack of efficacy 1.

Moderate Disease

If budesonide fails in moderate disease, escalate to prednisone 40-60 mg/day to induce remission 1.

• Evaluate symptomatic response to prednisone between 2-4 weeks 1.
• Corticosteroids are effective for induction but must never be used for maintenance therapy due to toxicity and lack of efficacy 1.

Moderate to Severe Disease (CDAI ≥ 220)

For moderate to severe Crohn's disease, use anti-TNF biologics (infliximab, adalimumab, certolizumab pegol) as first-line therapy, particularly in patients with poor prognostic factors 1, 3.

Poor Prognostic Factors Requiring Early Biologic Therapy:

• Complex disease (stricturing or penetrating) at presentation 1
• Perianal fistulizing disease 1
• Age under 40 years at diagnosis 1
• Need for steroids to control the index flare 1
• Extensive disease 1

First-Line Biologic Options:

Anti-TNF agents (strong recommendation, moderate certainty):

• Infliximab 1, 3
• Adalimumab 1, 4
• Certolizumab pegol 1

Alternative biologics:

• Ustekinumab (strong recommendation, moderate certainty) 1
• Vedolizumab (conditional recommendation, low certainty for induction, moderate for maintenance) 1
• Avoid natalizumab (conditional recommendation against) 1

The key paradigm shift is to use biologic agents early rather than delaying until after failure of 5-ASA and corticosteroids 1.

Severe Disease Requiring Hospitalization

For severe active Crohn's disease requiring hospitalization, use intravenous methylprednisolone 40-60 mg/day to induce symptomatic remission 1.

• Evaluate symptomatic response within 1 week to determine need for therapy modification 1.
• Transition to biologic therapy for maintenance once acute flare is controlled 1.

Maintenance Therapy

After Achieving Remission:

Corticosteroids must be discontinued—they are ineffective and toxic for maintenance 1.

Maintenance options based on induction therapy:

For Patients Who Achieved Remission with Corticosteroids:

• Thiopurines (azathioprine or mercaptopurine) can be used for maintenance in selected low-risk patients 1.
• Parenteral (subcutaneous or intramuscular) methotrexate for maintenance in corticosteroid-dependent patients 1.
• Avoid oral methotrexate—it is ineffective 1.
• Evaluate response within 12-16 weeks; modify therapy if corticosteroid-free remission not achieved 1.

For Patients on Biologic Therapy:

• Continue the same biologic agent that induced remission for maintenance 1.
• Anti-TNF agents, ustekinumab, and vedolizumab are all effective for maintenance 1.

Treatment of Specific Disease Manifestations

Perianal Fistulizing Disease

Infliximab is the recommended biologic for induction and maintenance of fistula remission (strong recommendation, moderate certainty) 1, 3.

• Combine biologic agents with antibiotics for induction of fistula remission (strong recommendation) 1.
• Avoid antibiotics alone—they are ineffective 1.
• Ensure no perianal abscess is present before initiating therapy 1.

Ileocecal Disease with Localized Involvement

Laparoscopic resection should be considered for localized ileocecal disease in patients failing or relapsing after initial medical therapy, or those preferring surgery to continued drug therapy 1.

Pediatric Dosing

Crohn's Disease (Age ≥6 years):

• 17-40 kg: Day 1: 80 mg, Day 15: 40 mg, then 20 mg every other week 4
• ≥40 kg: Day 1: 160 mg, Day 15: 80 mg, then 40 mg every other week 4

Ulcerative Colitis (Age ≥5 years):

• 20-40 kg: Day 1: 80 mg, Day 8: 40 mg, Day 15: 40 mg, then 40 mg every other week or 20 mg weekly 4
• ≥40 kg: Day 1: 160 mg, Day 8: 80 mg, Day 15: 80 mg, then 80 mg every other week or 40 mg weekly 4

Critical Pitfalls to Avoid

• Never use 5-ASA for Crohn's disease—it is ineffective for both induction and maintenance 1.
• Never use corticosteroids for maintenance—they cause toxicity without benefit 1.
• Never use thiopurine monotherapy for induction—it is too slow 1.
• Do not delay biologic therapy in moderate-to-severe disease with poor prognostic factors 1.
• Screen for latent tuberculosis before starting anti-TNF therapy 4.
• Discontinue therapy if serious infection develops 4.
• Monitor for lymphoma risk, particularly hepatosplenic T-cell lymphoma in young males on combination therapy 4.

Treatment Algorithm Summary

1. Assess severity using CDAI score and prognostic factors 1
2. Mild disease: Budesonide 9 mg/day → evaluate at 4-8 weeks 1
3. Moderate disease: Prednisone 40-60 mg/day if budesonide fails → evaluate at 2-4 weeks 1
4. Moderate-to-severe disease with poor prognosis: Anti-TNF biologic (infliximab, adalimumab) as first-line 1, 3
5. Maintenance: Continue effective biologic OR use thiopurines/parenteral methotrexate in selected patients 1
6. Never use corticosteroids or 5-ASA for maintenance 1