Mirikizumab for the Management of Ulcerative Colitis

Haens GD, Dubinsky M, Kobayashi T, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2023;388:2444–2455. Current treatments for ulcerative colitis (UC) come with limitations, including an increased risk of infections, non-response to primary therapy, and loss of clinical benefit over time. Mirikizumab, an investigational p19-directed monoclonal antibody against interleukin-23, showed efficacy in a phase 2 trial for the treatment of moderate to severe UC. The LUCENT trial was a phase 3, randomized, double-blinded, placebo-controlled, multi-center international study evaluating the efficacy and safety of mirikizumab in adult patients with moderate to severe UC. After the 12-week induction phase (n = 1162), a significantly higher proportion of patients receiving mirikizumab achieved the primary end point of clinical remission compared with those receiving placebo (24% vs 13%). Major secondary end points, including clinical response, endoscopic remission, remission of symptoms at weeks 4 and 12, clinical response in patients with previous treatment failure with a biologic agent or tofacitinib, and bowel urgency, were all improved in the mirikizumab group (P < .001 for all comparisons). Only patients who responded in the induction phase (n = 544) were included in the 40-week maintenance phase, which found significantly higher rates of clinical remission with mirikizumab compared with placebo (50% vs 25%). Among mirikizumab-treated patients who were in clinical remission at week 40, 98% were not taking glucocorticoids in the previous 3 months. Other outcomes, including maintenance of clinical, endoscopic, histologic-endoscopic mucosal, and bowel urgency remission, were all significantly higher in the mirikizumab group. Although the investigators reported a small and statistically insignificant number of adverse events, there were 15 opportunistic infections reported in the mirikizumab group (6 cases of herpes zoster, 4 cases of candidiasis and cytomegalovirus, and 1 case of intestinal tuberculosis) compared with 1 case of herpes zoster in the placebo group. Similarly, 8 cancers were reported in the mirikizumab group (5 gastrointestinal and 3 skin cancers) and none in the placebo group. Depression, elevated liver enzymes, nasopharyngitis, and arthralgia were also reported more frequently in the mirikizumab group. The study also observed frequent injection site reactions in the mirikizumab group compared with the placebo group. There were no anaphylactic reactions. Further randomized trials of longer duration are assessing the safety and efficacy of mirikizumab in UC (NCT03519945) and Crohn's disease (NCT03926130) which, followed by real-world outcomes data, might help position the drug within the inflammatory bowel disease landscape. In the meantime, the search for a lucent moon in the night sky goes on for patients with moderate to severe UC.