Treatment Options for Crohn's Disease
Advanced therapies are now recommended as first-line treatment for moderate to severe Crohn's disease due to their ability to modify disease course and achieve better long-term outcomes. 1
Initial Treatment Approach
- For mild to moderate Crohn's disease, systemic corticosteroids remain an effective initial therapy, regardless of disease location 1
- For less severe symptoms in ileocecal disease, ileal-release budesonide may be tried first, but prednisolone may be required if ineffective 1
- In teenagers where growth has not completed, or patients with diabetes or steroid intolerance, alternatives like exclusive enteral nutrition (EEN) should be considered 1
- 5-ASA compounds are not recommended for induction or maintenance of remission in Crohn's disease due to lack of efficacy 1
Treatment for Moderate to Severe Disease
- TNF inhibitors (infliximab, adalimumab, certolizumab pegol) are recommended for induction of remission in patients with moderate-to-severe Crohn's disease who haven't responded to conventional therapy 1
- Combination therapy with a thiopurine when starting infliximab is recommended for patients with moderate-to-severe Crohn's disease with inadequate response to conventional therapy 1
- Ustekinumab is recommended for induction of remission in patients with moderate-to-severe Crohn's disease with inadequate response to conventional therapy and/or anti-TNF therapy 1, 2
- For patients with primary non-response to TNF inhibitors, upadacitinib can be considered as an alternative option, along with ustekinumab and vedolizumab 3
Maintenance Therapy
- Systemic or locally acting corticosteroids should be avoided as maintenance therapy due to toxicity and lack of efficacy 1
- Azathioprine or mercaptopurine can be used as monotherapy for maintenance of remission 1
- Continuing azathioprine is superior to withdrawal for avoiding clinical relapse in patients already in remission on this therapy 1
- Immunomodulators (azathioprine, mercaptopurine, methotrexate) are effective for maintenance of remission and have corticosteroid-sparing effects 1, 4
Treatment Strategy Considerations
Early introduction of biologics may be considered in patients with aggressive disease course or "high-risk" poor prognostic factors, including: 1
- Complex (stricturing or penetrating) disease at presentation
- Perianal fistulising disease
- Age under 40 years at diagnosis
- Need for steroids to control the index flare
The REACT trial showed early use of monoclonal antibodies combined with immunosuppressants in high-risk patients was associated with significantly lower rates of complications, hospitalizations, and surgeries compared to conventional stepwise management 1
For localized ileocecal Crohn's disease, surgical resection should be considered for those failing or relapsing after initial medical therapy, or in those preferring surgery to continued drug therapy 1
Safety Considerations
- Combination therapy with anti-TNF agents and immunomodulators may be associated with higher risk for lymphoma and serious infections compared to anti-TNF monotherapy 1
- Infliximab crosses the placenta and infants exposed in utero should not receive live vaccines for at least 6 months after birth 5
- Common adverse reactions with ustekinumab in Crohn's disease include vomiting, nasopharyngitis, injection site erythema, and infections 2
- Thiopurine methyltransferase activity should be assessed before starting azathioprine or mercaptopurine to reduce risk of toxicity 6
Evolution of Treatment Paradigms
- Treatment approaches have evolved from traditional "step-up" (starting with corticosteroids and escalating to immunomodulators and biologics) to "top-down" (early use of biologics and immunomodulators) 7
- The "accelerated step-up" approach attempts to balance risks and benefits by quickly escalating to more effective therapies when needed, rather than prolonged trials of less effective medications 8
- Early effective treatment in moderate/severe Crohn's disease can lead to sustained, corticosteroid-free remission, with lower risk for hospitalizations and surgery 1
The optimal treatment strategy should be based on disease severity, location, behavior, and risk factors for poor outcomes, with the goal of achieving mucosal healing and preventing disease progression rather than just symptom control 7, 1.