What are the differences in biologic treatments for Crohn's disease (CD) and ulcerative colitis (UC)?

Biologic Therapies for Crohn's Disease vs Ulcerative Colitis

The key difference is that infliximab and risankizumab are superior first-line options for Crohn's disease, while infliximab alone stands out as the most effective first-line biologic for ulcerative colitis, with vedolizumab as an alternative. 1

Shared Biologics Across Both Conditions

TNF-α Antagonists

• Infliximab, adalimumab, and golimumab are FDA-approved for both CD and UC 2
• Infliximab demonstrates superior efficacy compared to adalimumab in both conditions, though the mechanism for this difference remains unclear despite their similar mechanism of action 1
• Standard adalimumab dosing is identical: 160 mg at week 0,80 mg at week 2, then 40 mg every other week for both CD and UC 3, 2

Integrin Antagonists

• Vedolizumab (anti-α4β7 integrin) is approved for both moderate-to-severe CD and UC 4, 5
• The gut-selective mechanism offers a favorable safety profile compared to systemic immunosuppression 5

IL-12/23 Inhibitors

• Ustekinumab is effective for both CD and UC, particularly in TNF-antagonist-exposed patients 1

Critical Differences in Efficacy by Disease

First-Line Therapy in Biologic-Naïve Patients

For Crohn's Disease:

• Infliximab and risankizumab are favored over ustekinumab, adalimumab, vedolizumab, and certolizumab 1
• No demonstrated superiority exists between infliximab and risankizumab 1
• Adalimumab shows strong efficacy with relative risk of 3.58 (95% CI: 2.42-5.29) for clinical remission within 4 weeks 3

For Ulcerative Colitis:

• Infliximab, golimumab, ozanimod, risankizumab, and guselkumab demonstrate superiority over adalimumab 1
• Infliximab is superior to vedolizumab, adalimumab, ustekinumab, and ozanimod 1
• Adalimumab is classified as "LOWER efficacy" compared to other options, with remission rates of only 19-21% at week 8 3, 6
• The AGA suggests using infliximab or vedolizumab rather than adalimumab for UC induction 1, 6

Second-Line Therapy After TNF-Antagonist Failure

For Crohn's Disease:

• In TNF-antagonist primary non-responders, ustekinumab is recommended and vedolizumab is suggested 1
• In secondary TNF-antagonist non-responders, ustekinumab remains preferred 1

For Ulcerative Colitis:

• Upadacitinib (JAK inhibitor) is superior to tofacitinib, ustekinumab, vedolizumab, adalimumab, and ozanimod in TNF-antagonist-exposed patients 1
• Ustekinumab is superior to vedolizumab or tofacitinib in this population 1
• In infliximab-exposed patients specifically, the AGA suggests ustekinumab or tofacitinib over vedolizumab or adalimumab 1
• Vedolizumab shows significantly better outcomes than adalimumab in IFX secondary failures (22.4% vs 48.0% failure rate, P=0.035) 7

UC-Specific Considerations

Dramatic Loss of Efficacy in Biologic-Exposed Patients

• Ozanimod demonstrates a striking pattern: highly effective in biologic-naïve patients (23% remission) but completely loses efficacy in patients exposed to 2 prior biologics (4% vs 3% placebo) 1
• This phenomenon is more pronounced in UC than CD and critically impacts therapy selection 1

JAK Inhibitors

• Tofacitinib and upadacitinib are approved only for UC, not CD 1
• FDA restricts JAK inhibitors from first-line use in the United States due to cardiovascular and malignancy concerns from the ORAL Surveillance trial, though these risks may not apply equally to IBD populations 1

CD-Specific Considerations

IL-23 Inhibitors

• Risankizumab shows comparable efficacy to infliximab in biologic-naïve CD patients 1
• Mirikizumab is available but risankizumab demonstrates superior efficacy within the same class 1

Combination Therapy

• Combining vedolizumab with thiopurines may reduce treatment failure in CD but not UC, based on observational data mirroring the SONIC trial design 1

Common Pitfalls

• Do not assume class equivalence: Infliximab outperforms adalimumab despite both being TNF-antagonists; upadacitinib outperforms tofacitinib despite both being JAK inhibitors 1
• Prior biologic exposure is not interchangeable: Recommendations for infliximab-exposed patients do not necessarily apply to adalimumab- or golimumab-exposed patients 1
• Avoid adalimumab for acute severe UC: Insufficient data support its use in this setting 3
• Consider drug concentrations: Trial efficacy may not reflect optimized dosing; adalimumab may perform better when therapeutic drug monitoring achieves adequate levels 1, 6