Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment: Interim Results From the LUCENT-3 Open-Label Extension Study (Ulcerative Colitis)

Mirikizumab is a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23. The efficacy and safety of mirikizumab in patients with moderately to severely active UC were evaluated in the LUCENT-1 induction trial and LUCENT-2 52-week maintenance trial.¹ Patients with a response to mirikizumab induction therapy were permitted to enroll in LUCENT-2, then were permitted to continue in the open-label, long-term extension study LUCENT-3. Sands and colleagues reported interim results from LUCENT-3 from 266 patients who had completed a total of 104 weeks of continuous treatment with mirikizumab, administered at 200 mg every 4 weeks as maintenance therapy.² The investigators noted that discontinuations or missing data were handled using nonresponder imputation (NRI), modified NRI, and observed case (OC) approaches. NRI is biased to show low remission rates, OC is biased to show high remission rates, and modified NRI uses multiple imputation to balance the bias of NRI and OC. The NRI strategy was primarily used and reported with this current dataset.

Figure 6.

Response and remission rates from the LUCENT-3 trial of patients with ulcerative colitis at week 104 of continuous mirikizumab treatment in the LUCENT-2 responders and remitters, NRI, mNRI, and OC.

^aClinical response: ≥2-point and ≥30% decrease in MMS from baseline; RB=0 or 1 or, RB ≥1-point decrease from baseline.

^bCorticosteroid-free remission: clinical remission at LUCENT-3 week 52 with no corticosteroid use for ≥12 weeks. cClinical remission: SF=0 or 1 with ≥1-point decrease in MMS from baseline; RB=0; and ES=0 or 1 (excluding friability). dEndoscopic remission: ES=1 or 1 (excluding friability); score ranges from 0 to 4; a lower score indicates less mucosal damage.

ES, endoscopic subscore; MMS, modified Mayo score; mNRI, modified NRI; NRI, nonresponder imputation; OC, observed case; RB, rectal bleeding; SF, stool frequency. Adapted from Sands et al. Abstract 70. Presented at: ACG 2023; October 20-25, 2023; Vancouver, Canada.²

Among patients who had a clinical response at week 52, the rate of clinical response at week 104 was 74.5%, and was similar among patients without (77.1%) or with (68.5%) prior biologic failure (Figure 6). Among patients with a clinical remission at week 52, the rate of clinical response at week 104 was 76.6%, and was 75.7% and 78.7% among patients without and with prior biologic failure, respectively.

In patients who had a clinical response at week 52, the rate of clinical remission at week 104 was 54.0%, and was similar among patients without (56.0%) or with (49.3%) prior biologic failure. Among patients with a clinical remission at week 52, the rate of clinical remission at week 104 was 65.6%, and was 67.3% and 61.7% among patients without and with prior biologic failure, respectively.

Similar trends were noted in the outcomes of week 104 symptomatic remission (67.8% in week 52 responders and 74.0% in week 52 remitters) as well as week 104 corticosteroid-free remission (52.7% in week 52 responders and 64.3% in week 52 remitters). Outcomes of week 104 endoscopic remission (65.3% in week 52 responders and 77.3% in week 52 remitters), week 104 HEMI (53.1% in week 52 responders and 66.2% in week 52 remitters), and week 104 HEMR (47.7% in week 52 responders and 59.1% in week 52 remitters) were also reported.

At week 104, similar proportions of patients reported a clinically meaningful improvement in bowel urgency (67.0% of week 52 responders and 67.3% of week 52 remitters) as well as bowel urgency remission (50.2% of week 52 responders and 51.3% of week 52 remitters).

A mixed models for repeated measures analysis was performed to determine the mean change in certain outcomes from baseline. There was little change observed from the beginning of the LUCENT-3 open-label extension study (week 52 of mirikizumab treatment) to week 104 in stool frequency (-1.68 at week 52 to -1.79 at week 104), rectal bleeding (-1.45 to -1.45), abdominal pain (-3.74 to -3.91), and urgency (-4.03 to -4.44).

No new safety signals were reported, and there was a low rate of mirikizumab discontinuation owing to adverse events. The most frequently reported adverse events included COVID-19 infection (12.1%), UC (7.6%), arthralgia (6.2%), headache (6.2%), and nasopharyngitis (5.9%).