Ulcerative colitis is a chronic disease characterized by inflammation of the colon and rectum, leading to symptoms such as rectal bleeding, increased stool frequency, bowel movement urgency, and abdominal pain. Current treatment options are limited, often associated with risks of infection, cancer, or loss of effectiveness over time.
According to the New England Journal of Medicine, a key factor in the inflammatory process of ulcerative colitis is interleukin-23 (IL-23). IL-23 has two subunits: p40, shared with interleukin-12, and p19, which is unique to IL-23. Several monoclonal antibodies have been developed to target IL-23 and have shown promising results in treating inflammatory bowel diseases like ulcerative colitis and Crohn’s disease.
One such monoclonal antibody is mirikizumab, a humanized IgG4-variant that specifically binds to the p19 subunit of IL-23. In a phase 2 trial involving patients with ulcerative colitis, mirikizumab demonstrated efficacy. Building on these findings, phase 3 trials, namely LUCENT-1 and LUCENT-2, were conducted to evaluate the efficacy and safety of mirikizumab in patients with moderately to severely active ulcerative colitis.
The results of these trials showed that mirikizumab significantly increased the percentage of patients achieving remission compared to placebo. The trials also included more rigorous goals, such as histologic–endoscopic mucosal remission, which requires the absence of mucosal neutrophils, indicating a resolution of acute inflammation. After one year of mirikizumab treatment, over 40% of patients achieved this remission.
Furthermore, mirikizumab demonstrated positive effects on bowel urgency, which is a crucial aspect for many patients with ulcerative colitis. Reductions in bowel urgency were reported by patients during the induction trial and were sustained throughout the maintenance trial.
While mirikizumab showed promise in treating ulcerative colitis, there were some adverse events observed. The incidence of herpes zoster infection was slightly higher in patients receiving mirikizumab compared to the placebo group. Gastric cancer and colorectal cancer cases were also detected, with some patients having been treated with mirikizumab. However, the severity of mucosal inflammation in these cases may have hindered their visualization during endoscopy at trial entry.
Elevations in liver enzyme levels were more frequent in the mirikizumab groups, and there were instances of depression, nasopharyngitis, and arthralgias reported. These side effects have been observed with other IL-23 inhibitors and therapies for ulcerative colitis. In conclusion, the phase 3 trials demonstrated that mirikizumab therapy had efficacy in both the induction and maintenance phases of ulcerative colitis treatment.
It showed positive results across various clinical, symptomatic, endoscopic, and histologic measures of the disease. Although there were some adverse events, the overall efficacy and safety profile of mirikizumab appear promising. Additional and longer trials are underway to further evaluate its effectiveness and safety in treating ulcerative colitis patients who have not responded well to conventional therapies.
