Mirikizumab Highly Effective in Treating Ulcerative Colitis and safely Maintaining Remission: NEJM

Explaining the study background, they said current therapies for ulcerative colitis are limited by increased infection risk and cancer, non-responsiveness to primary therapy and loss of clinical benefit over time.

Mirikizumab is a humanized IgG4-variant monoclonal antibody. It binds to subunit p19 of interleukin-2. In a phase 2 trial, it is efficacious in managing ulcerative colitis.

This was further investigated in the present study in two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with a history of moderately to severely active ulcerative colitis. The patients were randomly assigned (3:1 ) to receive 300 mg mirikizumab or placebo intravenously every four weeks for 12 weeks.

In the maintenance trial, patients responding to mirikizumab induction therapy were randomly assigned (2:1) to receive 200 mg mirikizumab or placebo, administered subcutaneously every four weeks for 40 weeks.

The primary endpoint studies were the clinical remission at week 12 in the induction trial and at week 40 in the maintenance trial.

Major secondary endpoints included Clinical response, endoscopic remission, and improvement in bowel-movement urgency were the major secondary endpoints studied.

The key results of the study are:

• 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial.
• There was a higher percentage of patients in the mirikizumab group than in the placebo group having clinical remission at week 12 of the induction trial (24.2% vs 13.3%) and at week 40 of the maintenance trial (49.9% vs 25.1%).
• Patients with mirikizumab had more adverse events of nasopharyngitis and arthralgia than those with a placebo.
• Patients treated with mirikizumab had an opportunistic infection (herpes zoster infection), and 8 had cancer (3 with colorectal cancer).
• Among Patients on placebo, 1 had herpes zoster infection, and none of the patients were reported to have cancer.

They said that in adults with moderately to severely active ulcerative colitis, we found a higher percentage of clinical remissions in patients on induction and maintenance therapy with mirikizumab. However, some patients treated with mirikizumab reported opportunistic infection or cancer.

The remaining questions are whether colorectal cancer detected was present at trial entry or not. This is not only a question but also a limitation.

More investigations are warranted to assess Mirikizumab’s efficacy and safety for treating ulcerative colitis.

Further reading:

https://www.nejm.org/doi/full/10.1056/NEJMoa2207940