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 suggests that different IL-23 inhibitors, such as mirikizumab, risankizumab, and guselkumab, have shown efficacy in inducing and maintaining clinical remission in patients with moderate-to-severe ulcerative colitis (UC) compared to placebo 1.
• The GRADE evidence profile indicates that the certainty of evidence for these agents is moderate, with relative effects ranging from 1.82 to 3.30 1.
• Although there is limited direct evidence on the effectiveness of switching between different IL-23 inhibitors, the fact that these agents have different mechanisms of action and binding specificities suggests that rotation may be beneficial in patients who fail initial treatment 1.
• Furthermore, the aga living clinical practice guideline on pharmacological management of moderate-to-severe UC notes that trials of mirikizumab, risankizumab, and guselkumab were all new since the previous 2020 guideline evidence synthesis, and that these agents were superior to placebo with moderate certainty of evidence 1.

Key Points

• Mirikizumab has been shown to induce clinical remission in 49.5% of patients with moderate-to-severe UC, compared to 23.9% with placebo 1.
• Risankizumab has been shown to induce clinical remission in 18.5% of patients with moderate-to-severe UC, compared to 6.2% with placebo 1.
• Guselkumab is currently under study, but has shown promise in treating psoriatic arthritis, a related condition 1.
• The decision to rotate to a different IL-23 inhibitor should be based on individual patient characteristics, safety, and cost considerations, as well as the experience of the physician 1.

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 in inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe Crohn's disease and ulcerative colitis 3, 4, 5, 6.
• The studies also suggest that different IL-23 inhibitors, such as risankizumab, mirikizumab, brazikumab, and guselkumab, have shown promising results in clinical trials 3, 5, 6.
• A systematic review and meta-analysis found that targeting IL-23 was significantly superior to placebo for inducing clinical and endoscopic remission and maintaining clinical remission in patients with Crohn's disease 4.
• Another study found that anti-IL-23 agents, such as ustekinumab and mirikizumab, have demonstrated efficacy in achieving clinical and endoscopic outcomes in ulcerative colitis with a favorable safety profile 5.

Potential for Rotation to a Different IL-23 Inhibitor

• While the studies do not directly address the effectiveness of rotating to a different IL-23 inhibitor, they suggest that IL-23 inhibitors are a promising therapeutic approach for Crohn's disease and ulcerative colitis 2, 3, 4, 5, 6.
• The studies also suggest that different IL-23 inhibitors may have different efficacy and safety profiles, which could inform decisions about rotation to a different IL-23 inhibitor 3, 5, 6.
• Further research is needed to determine the effectiveness of rotating to a different IL-23 inhibitor in patients who fail initial IL-23 inhibitor treatment 2, 3, 4, 5, 6.