Clinical Scorecard: Key Factors in Selecting IL-23p19 Inhibitors for Treating Inflammatory Bowel Disease: Importance and Implications

At a Glance

Key Highlights

• Three anti-IL23p19 monoclonal antibodies (Risankizumab, Mirikizumab, Guselkumab) are approved for moderate-to-severe Crohn’s disease and ulcerative colitis.
• Guselkumab uniquely offers subcutaneous induction dosing, improving patient adherence and reducing infusion-related risks.
• Selection of anti-IL23p19 therapy should consider patient preference, IBD phenotype, extra-intestinal manifestations, concomitant immune diseases, and prior advanced therapy exposure.

Guideline-Based Recommendations

Diagnosis

• Confirm moderate-to-severe Crohn’s disease or ulcerative colitis diagnosis before initiating anti-IL23p19 therapy.

Management

• Initiate treatment with induction dosing (typically three IV doses at weeks 0, 4, and 8) followed by maintenance SC injections every 4–8 weeks depending on the agent and indication.
• Consider Guselkumab for patients preferring subcutaneous induction to improve adherence and reduce infusion burden.
• Personalize agent selection based on IBD phenotype, extra-intestinal manifestations, concomitant immune-mediated diseases, and prior therapy exposure.

Monitoring & Follow-up

• Monitor clinical remission and endoscopic response at week 12 to assess treatment efficacy.
• Observe for infusion-related reactions if IV induction is used.

Risks

• Selective IL-23p19 inhibition may reduce susceptibility to some infections compared to IL-12/23 p40 blockade.
• Long-term safety data and real-world effectiveness in complex phenotypes such as perianal fistulizing Crohn’s disease require further study.

Patient & Prescribing Data

Adults with moderate-to-severe Crohn’s disease or ulcerative colitis, including those with IL-23 driven comorbidities like psoriasis.

Anti-IL23p19 agents demonstrate favorable efficacy and safety profiles; choice of agent and dosing regimen should be individualized to optimize adherence and outcomes.

Clinical Best Practices

• Use shared decision-making to incorporate patient preferences regarding mode of administration (IV vs SC).
• Tailor therapy choice to disease phenotype and presence of extra-intestinal or concomitant immune-mediated conditions.
• Consider Guselkumab’s unique SC induction as a strategy to reduce infusion center burden and improve patient convenience.
• Stay informed on emerging data regarding combination advanced therapies and their potential to improve long-term outcomes.
• Encourage participation in real-world studies to better define effectiveness in complex IBD phenotypes.

References

• European Medicines Agency and US FDA approvals for IL-23p19 inhibitors
• Phase 3 clinical trials demonstrating efficacy and safety of anti-IL23p19 agents
• IL-23 signaling pathway and immunopathogenesis in IBD