Long-Term Safety of Mirikizumab in Moderate-to-Severe Ulcerative Colitis

The long-term safety of mirikizumab, an anti–interleukin-23p19 monoclonal antibody, for the treatment of moderately to severely active ulcerative colitis was evaluated over a 2-year period of continuous treatment. This analysis pooled data from three phase 3 clinical trials—LUCENT-1 (induction phase), LUCENT-2 (maintenance phase), and LUCENT-3 (long-term extension phase)—and included 482 patients who were categorized as induction responders and extended-induction responders.

Key Findings:

1. Safety Profile Consistency:

• The safety profile of mirikizumab was consistent across both responder cohorts and aligned with previously reported findings from earlier studies.
• No new safety signals emerged during the 2-year treatment period, indicating a stable long-term safety profile.

2. Adverse Events (AEs):

• Most adverse events were mild to moderate in severity.
• The most frequently reported adverse events included:
• Nasopharyngitis
• COVID-19
• Arthralgia (joint pain)
• Ulcerative colitis symptom worsening
• Headache
• Serious adverse events (SAEs) occurred in fewer than 10% of patients, and treatment discontinuation due to adverse events was uncommon.

3. Infections:

• Infections were reported in approximately half of the patients, but the majority were mild.
• Rates of serious and opportunistic infections were low.

4. Injection-Site Reactions:

• Injection-site reactions were infrequent and decreased over time, particularly after the initial subcutaneous doses.

5. Subgroup Analysis:

• Rates of malignancy, major adverse cardiovascular events, depression, and hepatic abnormalities were low and comparable across clinically relevant subgroups.
• Older patients (aged 60 years or older) had a higher incidence of hypertension but did not show a disproportionate increase in serious infections or malignancies.
• Patients using corticosteroids and/or immunomodulators at baseline did not exhibit any significant safety concerns.

Overall Conclusion:

The findings from this integrated safety analysis support a favorable and stable long-term safety profile for mirikizumab in the treatment of moderately to severely active ulcerative colitis. The safety outcomes were consistent across various subgroups, including older patients and those receiving concomitant immunosuppressive therapy. These results provide reassurance for its use in clinical practice over extended treatment durations.