What is the preferred treatment between infliximab (chimeric monoclonal antibody) and ustekinumab (human monoclonal antibody) for Crohn's disease?

Infliximab vs Ustekinumab for Crohn's Disease

Both infliximab and ustekinumab are strongly recommended for moderate-to-severe Crohn's disease, with recent evidence showing comparable effectiveness for endoscopic and transmural remission in biologic-naïve patients. 1

Efficacy Comparison

• Both infliximab and ustekinumab are recommended by ECCO guidelines for the treatment of moderate-to-severe Crohn's disease with strong recommendations and moderate-quality evidence 2
• Recent prospective real-world cohort study (2025) demonstrated no significant differences between infliximab and ustekinumab in achieving endoscopic remission, endoscopic response, transmural remission, or clinical remission at weeks 14-26 and 44-56 1
• Post-hoc analysis of clinical trials showed comparable clinical remission rates at week 6 between infliximab (44.9%) and ustekinumab (37.9%) in biologic-naïve patients 3
• Treatment discontinuation rates by week 56 were similar between infliximab (24.4%) and ustekinumab (20.5%) groups 1

Advantages of Infliximab

• Infliximab has more extensive long-term safety and efficacy data as it has been in use longer 2, 4
• Infliximab showed higher C-reactive protein (CRP) remission rates at weeks 14-26 compared to ustekinumab, suggesting potentially faster inflammatory response 1
• Infliximab has established efficacy for fistulizing Crohn's disease with strong recommendation and moderate certainty of evidence 2
• Combination therapy with infliximab and thiopurines is strongly recommended for at least 6-12 months to improve efficacy and reduce immunogenicity 2

Advantages of Ustekinumab

• Ustekinumab is a fully human monoclonal antibody (vs chimeric for infliximab), which may result in lower immunogenicity 3
• Ustekinumab is recommended for patients who have previously failed anti-TNF therapy 2
• Ustekinumab does not require routine combination therapy with immunomodulators as immunogenicity rates are lower 2
• Ustekinumab has a favorable safety profile with no increased risk of serious infections or malignancies compared to placebo 2

Important Considerations

• Infliximab requires intravenous administration at 0,2, and 6 weeks for induction and every 8 weeks thereafter 2, 4
• Ustekinumab is administered with an initial intravenous dose followed by subcutaneous maintenance injections, which may be preferred by some patients 2
• Infliximab has higher immunogenicity rates (26-28%) which can be reduced with concomitant immunomodulator therapy 2
• Infliximab combination therapy with thiopurines increases efficacy but may be associated with higher risk for lymphoma and serious infections compared to monotherapy 2

Treatment Algorithm

1. For biologic-naïve patients with moderate-to-severe Crohn's disease:

   • Either infliximab or ustekinumab can be used as first-line biologic therapy with similar effectiveness 1
   • Consider infliximab with thiopurine combination if:
     • Perianal fistulizing disease is present 2
     • Rapid control of inflammation is needed (slightly faster CRP normalization) 1
     • Patient has no contraindications to immunomodulators 2
   • Consider ustekinumab if:
     • Patient prefers subcutaneous maintenance dosing 2
     • Concerns about immunogenicity exist 2
     • Contraindications to immunomodulators exist 2

2. For patients who have failed anti-TNF therapy:

   • Ustekinumab is strongly recommended 2

3. For patients with perianal fistulizing disease:

   • Infliximab is recommended with strong evidence 2

4. For patients with extraintestinal manifestations:

   • Infliximab may be preferred due to more extensive data in treating extraintestinal manifestations 5

Based on the most recent evidence, both medications demonstrate comparable effectiveness for the primary outcomes of endoscopic and clinical remission in Crohn's disease, with treatment choice depending on individual factors such as disease phenotype, comorbidities, and patient preferences 1.