IL-23 Monoclonal Antibodies as First-Line Treatment for Crohn's Disease
For patients with moderate-to-severe Crohn's disease, TNF inhibitors (infliximab and adalimumab) remain the recommended first-line treatment, while IL-23 inhibitors like risankizumab, guselkumab, and mirikizumab are currently positioned as second-line options after TNF antagonist failure. 1
Current Treatment Recommendations for Crohn's Disease
First-Line Therapy
- TNF inhibitors (infliximab, adalimumab) are recommended as first-line therapy for patients with moderate to severe Crohn's disease, particularly those with risk factors for poor prognosis 1
- The Canadian Association of Gastroenterology strongly recommends anti-TNF therapy to induce complete remission in patients with moderate to severe Crohn's disease who fail to achieve remission with corticosteroids, thiopurines, or methotrexate 1
Positioning of IL-23 Inhibitors
- IL-23 inhibitors are currently positioned as second-line therapy after TNF antagonist failure in the treatment algorithm for Crohn's disease 1
- Risankizumab has been approved for Crohn's disease treatment, while mirikizumab and guselkumab are still under study for this indication 1, 2
- The Italian Group for the Study of Inflammatory Bowel Disease notes that it remains unclear whether selective IL-23 inhibitors will have different efficacy compared to ustekinumab (IL-12/23 inhibitor) in Crohn's disease 1
Efficacy of IL-23 Inhibitors in Crohn's Disease
Risankizumab
- Risankizumab has been approved for the treatment of Crohn's disease and has demonstrated efficacy in clinical trials 1, 2
- The American Gastroenterological Association (AGA) strongly recommends risankizumab for moderate-to-severe ulcerative colitis over no treatment (strong recommendation, moderate to high certainty of evidence) 3
Mirikizumab
- In the VIVID-1 phase 3 trial, mirikizumab demonstrated efficacy as induction and maintenance treatment for patients with moderately-to-severely active Crohn's disease who had intolerance, inadequate response, or loss of response to standard therapy 4
- Mirikizumab achieved endoscopic response-composite in 38.0% of patients versus 9.0% on placebo (p<0.0001) 4
- The AGA suggests mirikizumab over no treatment for moderate-to-severe ulcerative colitis (conditional recommendation, moderate certainty of evidence) 1
Guselkumab
- Guselkumab is currently under study for Crohn's disease with promising preliminary results 1, 2
- The AGA recommends guselkumab over no treatment for moderate-to-severe ulcerative colitis (strong recommendation, moderate to high certainty of evidence) 1
Safety Considerations
- IL-23 inhibitors may have a more favorable safety profile compared to TNF antagonists, particularly regarding infectious complications 3, 5
- This safety advantage may be particularly relevant for older patients who are at increased risk for infections and malignancy 5
- Low rates of immunogenicity with IL-23 inhibitors suggest that concurrent immunosuppression may not be necessary 5
Treatment Algorithm for Crohn's Disease
- First-line therapy: TNF inhibitors (infliximab, adalimumab) for patients with moderate-to-severe Crohn's disease 1
- Second-line therapy: IL-23 inhibitors (risankizumab, mirikizumab, guselkumab) or ustekinumab (IL-12/23 inhibitor) for patients who fail TNF antagonist therapy 1, 2
- Special considerations: IL-23 inhibitors may be preferred over TNF antagonists in older patients or those at higher risk for infections and malignancy 5
Future Directions
- Phase III trials of mirikizumab and guselkumab for Crohn's disease are ongoing 1, 2
- Head-to-head comparisons between different treatment options for Crohn's disease are needed to better inform clinical decision-making 1
- Studies should focus on analyzing the efficacy of switching within the same drug class versus swapping between different drug classes 1