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Mirikizumab
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.
How effective is mirikizumab for the long-term control of symptoms of ulcerative colitis?
Patients had sustained stool frequency remission, rectal bleeding remission, bowel urgency remission, and improvement in abdominal pain after 52 weeks of continuous mirikizumab therapy (p<.001 vs placebo for all).
LUCENT-2 Study Design
LUCENT-2 is a 40-week, phase 3, multicenter, randomized, double-blind, parallel-arm, placebo-controlled, maintenance study that evaluated the safety and efficacy of mirikizumab, a p19-directed anti-interleukin (IL)-23 antibody, conducted in adult patients with moderately to severely active ulcerative colitis who completed the LUCENT-1 study.1
A total of 544 patients who received mirikizumab in LUCENT-1 and achieved a clinical response were rerandomized in a 2:1 ratio to receive subcutaneous mirikizumab 200 mg or placebo every 4 weeks for 40 weeks. Randomization was stratified by
- biologic failure status
- induction remission status
- baseline corticosteroid use, and
- geographic region (North America/Europe/other).1
Appendix shows definitions for the symptom endpoints, as mentioned in the following sections.
Stool Frequency Remission
At week 40 of LUCENT-2, 75.1% of patients who received mirikizumab had achieved stool frequency remission compared with 44.7% of patients who received placebo (p<.001) (Stool Frequency Remission at Week 40 of LUCENT-2).2
Figure 1 description: At week 40 of LUCENT-2, 75.1% of patients who received mirikizumab and 44.7% of patients who received placebo had stool frequency remission. The common risk difference (95% CI) for mirikizumab compared with placebo was 29.6 (21.2, 38.0) (p<.001).
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
a Common risk difference for MIRI vs PBO (95% CI).
The proportion of patients with stool frequency remission was significantly higher in the mirikizumab group than in the placebo group at each time point from weeks 8 through 40 of LUCENT-2 (p<.05) (Stool Frequency Remission Through Week 40 of LUCENT-2).2
Figure 2 description: At each time point from weeks 8 to 40 of LUCENT-2, a significantly greater proportion of patients who received mirikizumab than placebo had stool frequency remission (p<.05). The common risk difference (95% CI) for mirikizumab compared with placebo was 29.6 (21.2, 38.0) (p<.001) at week 40 of LUCENT-2.
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
* p<.05.
*** p<.001.
Rectal Bleeding Remission
At week 40 of LUCENT-2, 79.7% of patients who received mirikizumab had achieved rectal bleeding remission compared with 49.7% of patients who received placebo (p<.001) (Rectal Bleeding Remission at Week 40 of LUCENT-2).2
Figure 3 description: At week 40 of LUCENT-2, 79.7% of patients who received mirikizumab and 49.7% of patients who received placebo had rectal bleeding remission. The common risk difference (95% CI) for mirikizumab compared with placebo was 29.1 (20.8, 37.1) (p<.001).
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
a Common risk difference for MIRI vs PBO (95% CI).
The proportion of patients with rectal bleeding remission was significantly higher in the mirikizumab group than in the placebo group at each time point from weeks 8 through 40 of LUCENT-2 (p<.01) (Rectal Bleeding Remission Through Week 40 of LUCENT-2).3
Figure 4 description: At each time point from weeks 8 to 40 of LUCENT-2, a significantly greater proportion of patients who received mirikizumab than placebo had rectal bleeding remission (p<.01). The common risk difference (95% CI) for mirikizumab compared with placebo was 29.1 (20.8, 37.4) (p<.001) at week 40 of LUCENT-2.
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
** p<.01.
*** p<.001.
Symptomatic Remission
At week 40 of LUCENT-2, 71.0% of patients who received mirikizumab had achieved symptomatic remission compared with 39.7% of patients who received placebo (p<.001) (Symptomatic Remission at Week 40 of LUCENT-2).3
Figure 5 description: At week 40 of LUCENT-2, 71.0% of patients who received mirikizumab and 39.7% of patients who received placebo had symptomatic remission. The common risk difference (95% CI) for mirikizumab compared with placebo was 30.2 (21.9, 38.6) (p<.001).
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
a Common risk difference for MIRI vs PBO (95% CI).
At week 40 of LUCENT-2, 69.7% of patients who received mirikizumab had stable maintenance of symptomatic remission compared with 38.4% of patients who received placebo (p<.001) (Stable Maintenance of Symptomatic Remission at Week 40 of LUCENT-2).2
Figure 6 description: At week 40 of LUCENT-2, 69.7% of patients who received mirikizumab and 38.4% of patients who received placebo had symptomatic remission. The common risk difference (95% CI) for mirikizumab compared with placebo was 31.0 (20.7, 41.2) (p<.001).
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
a Common risk difference for MIRI vs PBO (95% CI).
The proportion of patients with symptomatic remission was significantly higher in the mirikizumab group than in the placebo group at each time point from weeks 8 through 40 of LUCENT-2 (p<.05) (Symptomatic Remission Through Week 40 of LUCENT-2).2
Figure 7 description: At each time point from weeks 8 to 40 of LUCENT-2, a significantly greater proportion of patients who received mirikizumab than placebo had symptomatic remission (p<.001). The common risk difference (95% CI) for mirikizumab compared with placebo was 30.2 (21.9, 38.6) (p<.001) at week 40 of LUCENT-2.
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
* p<.05.
** p<.01.
*** p<.001.
Bowel Urgency Improvement and Remission
The least-squares mean improvement from baseline in the Urgency Numeric Rating Scale (NRS) was significantly greater in the mirikizumab group than in the placebo group at each time point from weeks 12 through 40 of LUCENT-2 (p<.05) (Bowel Urgency Numeric Rating Scale Through Week 40 of LUCENT-2).2
Figure 8 description: At each time point from weeks 12 to 40 of LUCENT-2, the least-squares mean change from baseline in the Urgency Numeric Rating Scale was significantly greater for the mirikizumab group than the placebo group (p<.05). At week 40 of LUCENT-2, the least-squares mean change from baseline was -3.80 for mirikizumab and -2.74 for placebo (least-squares mean difference [95% CI], -1.06 [-1.51, -0.61]).
Abbreviations: LSM = least-squares mean; MIRI = mirikizumab; MMRM = mixed model for repeated measures; PBO = placebo; SC = subcutaneous.
* p<.05.
*** p<.001.
Of the patients with an Urgency NRS of at least 3 at induction baseline, the proportion of patients with bowel urgency remission was significantly higher in the mirikizumab group than in the placebo group at each time point from weeks 8 through 40 of LUCENT-2 (p<.05) (Bowel Urgency Remission Through Week 40 of LUCENT-2).2
Figure 9 description: At each time point from weeks 8 to 40 of LUCENT-2, a significantly greater proportion of patients who received mirikizumab than placebo had bowel urgency remission (p<.05).
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
* p<.05.
** p<.01.
*** p<.001.
Note: The analysis includes patients with Urgency Numeric Rating Scale ≥3 at induction baseline.
Abdominal Pain Improvement
The proportion of patients with abdominal pain improvement was significantly higher in the mirikizumab group than in the placebo group at each time point from weeks 16 through 40 of LUCENT-2 (p<.05) (Improvement in Abdominal Pain Through Week 40 of LUCENT-2 ).2
Figure 10 description: At each time point from weeks 16 to 40, a significantly greater proportion of patients who received mirikizumab than placebo had improvement in abdominal pain (p<.05). The common risk difference (95% CI) for mirikizumab compared with placebo was 27.4 (18.32, 36.4) (p<.001) at week 40 of LUCENT-2.
Abbreviations: MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo; SC = subcutaneous.
* p<.05.
*** p<.001.
Note: The analysis includes patients with abdominal pain NRS ≥3 at induction baseline.
Additional Information
Additional safety and efficacy data from the mirikizumab ulcerative colitis registration studies are available in the following document:
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Dubinsky MC, Irving PM, Li X, et al. Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study. Abstract presented at: Digestive Disease Week; May 24, 2022; San Diego, California.
2Dignass A, Danese S, Matsuoka K, et al. Sustained symptom control with mirikizumab in patients with moderately to severely active ulcerative colitis in the LUCENT-2 maintenance trial. Abstract presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
3Dignass A, Danese S, Matsuoka K, et al. Sustained symptom control with mirikizumab in patients with moderately to severely active ulcerative colitis in the LUCENT-2 maintenance trial. Poster presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
4Danese S, Dignass A, Matsuoka K, et al. Early symptom control with mirikizumab in patients with moderately to severely active ulcerative colitis in the LUCENT-1 induction trial. Abstract presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
5Dubinsky MC, Irving PM, Panaccione R, et al. Incorporating patient experience into drug development for ulcerative colitis: development of the Urgency Numeric Rating Scale, a patient-reported outcome measure to assess bowel urgency in adults. J Patient Rep Outcomes. 2022;6(1):31. https://dx.doi.org/10.1186/s41687-022-00439-w
6Dubinsky MC, Delbecque L, Lewis JD, et al. Psychometric validation and interpretation of a patient-reported outcomes instrument to assess bowel urgency among adults with moderate to severe ulcerative colitis. Abstract presented at: 17th Congress of the European Crohn’s and Colitis Organisation (ECCO Virtual); February 16-19, 2022. Accessed June 15, 2022. https://www.ecco-ibd.eu/publications/congress-abstracts/item/p138-psychometric-validation-and-interpretation-of-a-patient-reported-outcomes-instrument-to-assess-bowel-urgency-among-adults-with-moderate-to-severe-ulcerative-colitis.html
Appendix
Outcome |
Definition |
Stool frequency remission |
Stool frequency subscore of 0, or stool frequency subscore of 1 with ≥1-point decrease from baseline. |
Rectal bleeding remission |
Rectal bleeding subscore of 0. |
Symptomatic remission |
Stool frequency subscore of 0, or stool frequency subscore of 1 with ≥1-point decrease from baseline, and rectal bleeding subscore of 0. |
Stable maintenance of symptomatic remission |
Symptomatic remission for at least 7 of 9 visits from weeks 4 to 36 and also at week 40, among patients in symptomatic remission and clinical response at the end of LUCENT-1. |
Bowel urgency NRS |
The bowel urgency NRS is an 11-point scale ranging from
|
Bowel urgency remission |
Defined as Urgency NRS=0 or 1 among patients induced into clinical response with mirikizumab in LUCENT-1 and had Urgency NRS ≥3 at induction baseline. |
Improvement in abdominal pain |
Improvement ≥30% from induction baseline in patients with a baseline abdominal pain NRS ≥3. |
Abbreviation: NRS = Numeric Rating Scale.
Date of Last Review: October 11, 2022