What is the recommended treatment approach for moderate Crohn's disease?

Treatment of Moderate Crohn's Disease

For patients with moderate Crohn's disease, anti-TNF therapy (infliximab, adalimumab) is recommended as first-line therapy, particularly for those with risk factors for poor prognosis. 1

First-Line Treatment Options

Anti-TNF Biologics

• Anti-TNF agents (infliximab, adalimumab) are recommended as first-line therapy for moderate-to-severe Crohn's disease with risk factors of poor prognosis 1
• Infliximab is administered intravenously at 5 mg/kg at weeks 0,2, and 6 for induction, followed by maintenance every 8 weeks 1, 2
• Adalimumab is given subcutaneously with an induction dose of 160 mg, then 80 mg two weeks later, followed by 40 mg every two weeks for maintenance 1, 3
• Patients should be evaluated for response to anti-TNF induction therapy between 8-12 weeks to determine if therapy modification is needed 1

Combination Therapy

• When starting infliximab, combination therapy with a thiopurine is recommended to improve efficacy and reduce immunogenicity 1
• For adalimumab, combination with methotrexate may be more effective than monotherapy, though evidence is less robust 1
• Combination therapy has shown better outcomes for remission induction compared to monotherapy 1

Alternative First-Line Options

Ustekinumab

• Ustekinumab is recommended for induction of remission in patients with moderate-to-severe Crohn's disease 1
• Particularly useful in patients who have inadequate response to conventional therapy or anti-TNF therapy 1

Vedolizumab

• Vedolizumab is suggested as an alternative to certolizumab pegol for induction of remission 1
• May be considered in patients who prioritize a potentially better safety profile over speed of action 1

Second-Line Treatments

For Primary Non-Responders to Anti-TNF

• Ustekinumab is strongly recommended for patients who never responded to anti-TNF therapy 1
• Vedolizumab is suggested as an alternative for induction of remission in primary non-responders 1

For Secondary Non-Responders to Anti-TNF

• For patients who initially responded but later lost response to infliximab, adalimumab or ustekinumab are recommended 1
• If adalimumab was the first-line drug with subsequent loss of response, infliximab may be considered as a second-line agent 1
• Dose optimization guided by therapeutic drug monitoring is suggested for patients who lose response to anti-TNF maintenance therapy 1

Corticosteroids

• In patients with moderate Crohn's disease who have failed budesonide, prednisone 40-60 mg/day is suggested to induce remission 1
• Patients should be evaluated for response to prednisone between 2-4 weeks 1
• Corticosteroids are NOT recommended for maintenance of remission due to significant side effects 1, 4
• Side effects include bone loss, metabolic complications, increased intraocular pressure, and increased risk of infections 4

Immunomodulators

Thiopurines (Azathioprine, 6-Mercaptopurine)

• Not recommended as monotherapy for induction of remission 1
• May be used for maintenance of remission in selected patients who achieved remission on corticosteroids 1
• Patients should be monitored for response, with therapy modification if corticosteroid-free remission is not achieved within 12-16 weeks 1

Methotrexate

• Parenteral (subcutaneous or intramuscular) methotrexate is suggested for induction and maintenance of remission 1
• Particularly useful in corticosteroid-dependent/resistant moderate-to-severe Crohn's disease 1
• Oral methotrexate is not recommended due to limited efficacy 1

Treatments NOT Recommended

• 5-ASA or sulfasalazine are not recommended for moderate Crohn's disease 1
• Natalizumab is not recommended due to risk of progressive multifocal leukoencephalopathy (PML) 1
• Oral methotrexate is not recommended due to limited efficacy 1
• Thiopurine monotherapy is not recommended for induction of remission 1

Treatment Algorithm

1. First-line therapy: Anti-TNF (infliximab or adalimumab), preferably in combination with thiopurine or methotrexate 1
2. Alternative first-line: Ustekinumab or vedolizumab, especially in patients with contraindications to anti-TNF therapy 1
3. For primary non-response to anti-TNF: Switch to ustekinumab or vedolizumab 1
4. For secondary non-response to anti-TNF:
   • If on infliximab, switch to adalimumab or ustekinumab
   • If on adalimumab, consider infliximab or ustekinumab 1
5. Dose optimization for partial responders to anti-TNF, guided by therapeutic drug monitoring 1

Monitoring

• Evaluate response to anti-TNF induction therapy between 8-12 weeks 1
• Assess response to prednisone between 2-4 weeks 1
• Monitor for immunosuppression-related complications including infections and malignancy 2, 3
• Test for tuberculosis before starting anti-TNF therapy 2, 3

Important Considerations

• Early introduction of biologics (with or without immunomodulators) is suggested rather than delaying until after failure of mesalamine and/or corticosteroids 1
• Combination therapy with anti-TNF and immunomodulators may increase efficacy but also increases risk of adverse events, including infections and certain malignancies 2, 3
• The risk-benefit profile should be carefully considered, especially in young males (risk of hepatosplenic T-cell lymphoma with combination therapy) 2, 3