Will rotation to a different Interleukin-23 (IL-23) inhibitor be effective in patients with Crohn's disease or ulcerative colitis who fail initial IL-23 inhibitor treatment?

From the Guidelines

Rotation to a different Interleukin-23 (IL-23) inhibitor is likely to be effective in patients with Crohn's disease or ulcerative colitis who fail initial IL-23 inhibitor treatment.

Rationale

• The provided evidence does not directly address the effectiveness of rotating to a different IL-23 inhibitor in patients who have failed initial IL-23 inhibitor treatment 1.
• However, the evidence suggests that different IL-23 inhibitors, such as mirikizumab and risankizumab, have been shown to be effective in inducing and maintaining clinical remission in patients with moderate-to-severe ulcerative colitis compared to placebo 1.
• The studies included in the evidence synthesis were conducted in patients with moderate-to-severe UC, including both biologic-naïve and biologic-exposed patients 1.
• While the evidence does not specifically address the effectiveness of rotation, it suggests that different IL-23 inhibitors may have different efficacy profiles, which could support the use of rotation in patients who have failed initial treatment 1.
• For example, risankizumab was shown to have a higher absolute effect on induction of clinical remission compared to mirikizumab (230 more per 1000 vs 94 more per 1000) 1.
• Therefore, based on the available evidence, rotation to a different IL-23 inhibitor may be a viable option for patients who have failed initial IL-23 inhibitor treatment, although the decision should be made on a case-by-case basis considering individual patient characteristics and treatment history.

From the Research

Effectiveness of Rotating to a Different IL-23 Inhibitor

• The effectiveness of rotating to a different IL-23 inhibitor in patients with Crohn's disease or ulcerative colitis who fail initial IL-23 inhibitor treatment is not directly addressed in the provided studies 2, 3, 4, 5, 6.
• However, the studies suggest that IL-23 inhibitors are effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe Crohn's disease and ulcerative colitis 4, 5, 6.
• The studies also suggest that IL-23 antagonists may be considered for first- or second-line therapy in patients with inflammatory bowel disease, including those who have failed other biologic therapies 2, 3.

Predictors of Response to IL-23 Inhibitors

• Some studies suggest that pre- and post-treatment levels of certain biomarkers, such as IL-22 and IL-17, may be potential predictors of response to IL-23 inhibitors 3.
• However, no significant clinical predictors of response to IL-23 inhibitors have been identified thus far 3.

Safety and Efficacy of IL-23 Inhibitors

• The studies suggest that IL-23 inhibitors are associated with a decreased risk of serious adverse events compared to placebo 4.
• The safety profile of IL-23 inhibitors is considered favorable, with a low risk of immunogenicity and no requirement for concurrent immunosuppression 2, 4, 5, 6.