Can a Patient Use Risankizumab with a Contraindication to Infliximab?
Yes, risankizumab is an appropriate alternative for patients with contraindications to infliximab, as it has a distinct mechanism of action (IL-23 inhibition vs TNF antagonism) and does not share the same contraindications. 1
Guideline Support for Risankizumab as Alternative Therapy
The American Gastroenterological Association (AGA) 2024 guidelines explicitly recommend risankizumab as an advanced immunosuppressive therapy for inflammatory bowel disease, positioning it alongside but distinct from TNF antagonists like infliximab. 1
For patients with contraindications to TNF antagonists, the AGA conditionally recommends using IL-23 inhibitors (such as risankizumab) or other non-TNF biologics over conventional immunosuppressants. 1
Key Differences in Safety Profile
Infliximab-Specific Contraindications Not Shared by Risankizumab:
Heart failure: Infliximab is specifically contraindicated at high doses (>5 mg/kg) in patients with moderate-to-severe heart failure and has been associated with worsening cardiac function. 1 Risankizumab does not carry this contraindication. 2
Demyelinating disease: TNF antagonists including infliximab are contraindicated in patients with demyelinating disorders. 1 IL-23 inhibitors like risankizumab have not been shown to worsen these conditions. 1
Hepatotoxicity risk profile: While both agents require monitoring, infliximab is specifically contraindicated for immune-related hepatitis. 1 Risankizumab has a different hepatotoxicity profile requiring baseline and induction monitoring but is not contraindicated in the same contexts. 2
Risankizumab's Only Contraindication
The sole contraindication to risankizumab is a history of serious hypersensitivity reaction to risankizumab-rzaa or any of its excipients. 2 This is a drug-specific hypersensitivity and does not overlap with infliximab contraindications.
Clinical Efficacy Supporting Use as Alternative
Risankizumab demonstrated superior efficacy compared to ustekinumab in head-to-head trials, with 31.8% achieving endoscopic remission at week 48 versus 16.2% with ustekinumab (adjusted difference 15.6 percentage points, P<0.001). 3
In biologic-experienced patients (including those who failed TNF antagonists), risankizumab achieved clinical remission rates of 42-45% at week 12 in the ADVANCE and MOTIVATE trials. 4
The AGA guidelines note risankizumab may have a lower rate of infectious complications compared to TNF antagonists, which may benefit patients at higher infection risk. 5, 6
Specific Clinical Scenarios
If the contraindication to infliximab is:
Congestive heart failure or demyelinating disease: Risankizumab is preferred as it does not worsen these conditions. 1
Tuberculosis or recurrent infections: While risankizumab still requires TB screening before initiation 2, it may have a more favorable infection profile than TNF antagonists. 6 However, sulfasalazine would be preferred if active infection risk is extremely high. 1
Immune-related hepatitis: Risankizumab can be used with appropriate hepatic monitoring, whereas infliximab is specifically contraindicated. 1, 2
Monitoring Requirements for Risankizumab
Obtain liver enzymes and bilirubin levels prior to initiating treatment and during induction up to at least 12 weeks. 2
Evaluate for tuberculosis infection prior to initiating treatment. 2
Complete all age-appropriate vaccinations before starting therapy; avoid live vaccines during treatment. 2
Do not initiate in patients with clinically important active infection. 2
Common Pitfall to Avoid
Do not assume that a contraindication to one biologic class (TNF antagonists) applies to all biologics. Risankizumab's IL-23 inhibition mechanism is fundamentally different from TNF antagonism, resulting in a distinct safety profile and different contraindications. 1, 2