Long-term use of mirikizumab does not raise new safety signals

A recent study has demonstrated the long-term safety of mirikizumab in patients with moderate to severe active ulcerative colitis (UC), with no new significant safety concerns.

“The safety profiles for cohorts who had received 12-week and 24-week inductions were consistent with previously reported safety profiles and were unaffected by older age or use of corticosteroids and/or immunomodulators,” according to the researchers.

The research team assessed patients who underwent induction (LUCENT-1) and maintenance (LUCENT-2) and entered long-term maintenance (LUCENT-3) in two cohorts: induction responders (n=333) and extended-induction responders (n=149). Participants in both cohorts received continuous treatment with mirikizumab for up to 104 weeks.

Finally, the researchers evaluated adverse events (AEs) in the two cohorts and within subsets of patients aged ≥60 years and those using corticosteroids, immunomodulators, or both at baseline.

The safety profile of patients was consistent across cohorts and subsets. The most common AEs were nasopharyngitis, arthralgia, COVID-19, headache, and UC (worsening/reoccurrence of symptoms). Moreover, less than one in 10 of patients in both cohorts reported serious AEs. [Am J Gastroenterol 2025;120:2857-2866]

Infections (mostly mild), cerebrocardiovascular (CCV) events, and malignancies occurred in 47.4 percent, 49.7 percent, and 0.9 percent of induction responders, respectively. The respective AEs also occurred in 1.3 percent, 0 percent, and 3.4 percent of extended-induction responders.

Injection-site reactions occurred in 10.2 percent of induction responders and 8.1 percent of extended-induction responders. These reactions decreased over time.

Similar safety profiles were observed in patient subsets and in the whole population, except for hypertension, which occurred more frequently in patients aged ≥60 years.

“These data support up to 2 years of administration of mirikizumab to patients with moderate to severely active UC, [with] a favourable benefit-risk profile, regardless of the treatment regimen used,” the researchers said.

AEs of special interest

The most common AEs seen in this study were similar to those previously reported for mirikizumab and those documented for ustekinumab, another biologic used in the treatment of moderate to severe UC targeting interleukin (IL)-12/IL-23. [N Engl J Med 2023;3882444-2455; Inflamm Bowel Dis 2024;30:2245-2258; Am J Gastroenterol 2024;119:910-921; Aliment Pharmacol Ther 2020;52:1658-1675]

Notably, herpes zoster was the most common opportunistic infection among AEs. Four out of seven cases occurred in Asians, who appeared to be more vulnerable to this infection. [BMC Infect Dis 2017;17:213; J Am Acad Dermatol 2017;77:302-309]

Among other AEs of special interest, CCV events occurred in around 1 percent of patients, while injection-site reactions, depression, and hepatic-related events occurred in <11 percent. Injection-site reactions declined over time and after the first dose.

In LUCENT-3, five malignancies were reported among extended-induction responders and were not previously reported due to differences in study population. Three of these malignancies were skin cancer, which are common in patients with inflammatory bowel disease. [Gastroenterology 2012;143:390-399.e1; N Engl J Med 2023;388:2444-2455; Inflamm Bowel Dis 2024;30:2245-2258]

“Continuous administration of mirikizumab up to 2 years does not lead to new safety concerns,” the researchers said. “The safety profile of mirikizumab is unaffected by treatment regimen, older age, or use of corticosteroids and/or immunomodulators at baseline.”