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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 soon does mirikizumab start working for the symptoms of ulcerative colitis?
As early as week 2, mirikizumab was associated with significantly greater improvements in stool frequency, rectal bleeding, bowel urgency, and fatigue as well as higher stool frequency remission rates than placebo.
LUCENT-1 Study Design
LUCENT-1 is a 12-week, phase 3, multicenter, randomized, double-blind, parallel, placebo-controlled study of mirikizumab, a p19-directed anti-interleukin(IL)-23 antibody. The study was conducted to evaluate efficacy and safety in adult patients with moderately-to-severely active ulcerative colitis, with a Modified Mayo score of 4 to 9 points and centrally read Mayo endoscopic subscore ≥2, who had an inadequate response, loss of response, or an intolerance to corticosteroids, immunosuppressants, biologic therapies, or tofacitinib.1
A total of 1281 patients were randomized in a 3:1 ratio to receive intravenous mirikizumab 300 mg or placebo every 4 weeks. Randomization was stratified by
- biologic failure status
- baseline corticosteroid use
- baseline disease activity as measured by the Modified Mayo score, and
- world region.1
Ulcerative Colitis Symptom Control During the 12-Week LUCENT-1 Induction Study
Appendix shows definitions for the symptom endpoints and outcomes, as mentioned in the following sections.
Improvement in Stool Frequency
As early as week 2, patients who received mirikizumab had significantly greater reductions from baseline in stool frequency compared with placebo (p<.05) (Change in Stool Frequency in LUCENT-1).2,3
Figure 1 description: The least-squares mean change from baseline in stool frequency was significantly greater in the mirikizumab group than in the placebo group at weeks 2 (p<.05), 4 (p<.001), 8 (p<.001), and 12 (p<.001). At week 12, the least-squares mean reduction from baseline in stool frequency was 1.06 for mirikizumab and 0.71 for placebo.
Abbreviations: IV = intravenous; LSM = least-squares mean; MIRI = mirikizumab; MMRM = mixed measures repeated model; PBO = placebo.
* p<.05.
*** p<.001.
Improvement in Rectal Bleeding
As early as week 2, patients who received mirikizumab had significantly greater reductions from baseline in rectal bleeding compared with placebo (p<.01) (Change in Rectal Bleeding in LUCENT-1).2,3
Figure 2 description: The least-squares mean change from baseline in rectal bleeding was significantly greater in the mirikizumab group than in the placebo group at weeks 2 (p<.01), 4 (p<.001), 8 (p<.001), and 12 (p<.001). At week 12, the least-squares mean reduction from baseline in rectal bleeding was 1.01 for mirikizumab and 0.75 for placebo.
Abbreviations: IV = intravenous; LSM = least-squares mean; MIRI = mirikizumab; MMRM = mixed measures repeated model; PBO = placebo.
** p<.01.
*** p<.001.
Improvement in Bowel Urgency
As early as week 2, patients who received mirikizumab had significantly greater reductions from baseline in bowel urgency compared with placebo (p<.01) (Change in Bowel Urgency in LUCENT-1).2,3
Figure 3 description: The least-squares mean change from baseline in bowel urgency was significantly greater in the mirikizumab group than in the placebo group at weeks 2 (p<.01), 4 (p<.001), 8 (p<.001), and 12 (p<.001). At week 12, the least-squares mean reduction from baseline in bowel urgency was 2.59 for mirikizumab and 1.63 for placebo.
Abbreviations: IV = intravenous; LSM = least-squares mean; MIRI = mirikizumab; MMRM = mixed measures repeated model; PBO = placebo.
** p<.01.
*** p<.001.
Stool Frequency Remission
As early as week 2, a significantly greater proportion of patients who received mirikizumab achieved stool frequency remission than did patients who received placebo (p<.05) (Stool Frequency Remission Rates in LUCENT-1).2,3
Figure 4 description: The proportion of patients who achieved stool frequency remission was significantly higher in the mirikizumab group than in the placebo group at weeks 2 (p<.05), 4 (p<.001), 8 (p<.001), and 12 (p<.001). At week 12, 57.0% of patients in the mirikizumab group and 39.8% of patients in the placebo group had achieved stool frequency remission.
Abbreviations: IV = intravenous; MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo.
* p<.05.
*** p<.001.
Note: Stool frequency remission is defined as a stool frequency subscore of 0, or stool frequency subscore of 1 with ≥1-point decrease from baseline.
Rectal Bleeding Remission
As early as week 4, a significantly greater proportion of patients who received mirikizumab achieved rectal bleeding remission than did patients who received placebo (p<.05) (Rectal Bleeding Remission Rates in LUCENT-1).2,3
Figure 5 description: The proportion of patients who achieved rectal bleeding remission was significantly higher in the mirikizumab group than in the placebo group at weeks 4 (p<.05), 8 (p<.001), and 12 (p<.001). At week 12, 63.9% of patients in the mirikizumab group and 43.9% of patients in the placebo group had achieved rectal bleeding remission.
Abbreviations: IV = intravenous; MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo.
* p<.05.
*** p<.001.
Note: Rectal bleeding remission is defined as a rectal bleeding subscore of 0.
Symptomatic Response
As early as week 2, a significantly greater proportion of patients who received mirikizumab achieved symptomatic response than did patients who received placebo (p<.01) (Symptomatic Response Rates in LUCENT-1).2,3
Figure 6 description: The proportion of patients who achieved symptomatic response was significantly higher in the mirikizumab group than in the placebo group at weeks 2 (p<.01), 4 (p<.001), 8 (p<.001), and 12 (p<.001). At week 12, 72.0% of patients in the mirikizumab group and 52.4% of patients in the placebo group had achieved symptomatic response.
Abbreviations: IV = intravenous; MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo.
** p<.01.
*** p<.001.
Note: Symptomatic response is defined as a reduction ≥30% from baseline in the sum of stool frequency and rectal bleeding subscores.
Symptomatic Remission
As early as week 4, a significantly greater proportion of patients who received mirikizumab achieved symptomatic remission than did patients who received placebo (p<.001) (Symptomatic Remission Rates in LUCENT-1).2,3
Figure 7 description: The proportion of patients who achieved symptomatic remission was significantly higher in the mirikizumab group than in the placebo group at weeks 4 (p<.001), 8 (p<.001), and 12 (p<.001). At week 12, 45.5% of patients in the mirikizumab group and 27.9% of patients in the placebo group had achieved symtpomatic remission.
Abbreviations: IV = intravenous; MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo.
*** p<.001.
Note: Symptomatic remission is defined as (1) a stool frequency subscore of 0, or stool frequency subscore of 1 with ≥1-point decrease from baseline, and (2) rectal bleeding subscore of 0.
Bowel Urgency Clinically Meaningful Improvement
As early as week 4, a significantly greater proportion of patients who received mirikizumab achieved a clinically meaningful improvement in bowel urgency than did patients who received placebo (p<.05) (Bowel Urgency Clinically Meaningful Improvement in LUCENT-1).2,3
Figure 8 description: The proportion of patients who achieved a clinically meaningful improvement in bowel urgency was significantly higher in the mirikizumab group than in the placebo group at weeks 4 (p<.05), 8 (p<.001), and 12 (p<.001). At week 12, 48.7% of patients in the mirikizumab group and 32.2% of patients in the placebo group had achieved a clinically meaningful improvement in bowel urgency.
Abbreviations: IV = intravenous; MIRI = mirikizumab; NRI = nonresponder imputation; NRS = Numeric Rating Scale; PBO = placebo.
* p<.05.
*** p<.001.
Note: Clinically meaningful is defined as an improvement ≥3 points in the Urgency NRS in patients with a baseline Urgency NRS ≥3.
Bowel Urgency Remission
At week 8, a significantly greater proportion of patients who received mirikizumab achieved bowel urgency remission than did patients who received placebo (p<.01) (Bowel Urgency Remission Rates in LUCENT-1).2,3
Figure 9 description: The proportion of patients who achieved bowel urgency remission was significantly higher in the mirikizumab group than in the placebo group at weeks 8 (p<.01) and 12 (p<.001). At week 12, 22.1% of patients in the mirikizumab group and 12.3% of patients in the placebo group had achieved bowel urgency remission.
Abbreviations: IV = intravenous; MIRI = mirikizumab; NRI = nonresponder imputation; NRS = Numeric Rating Scale; PBO = placebo.
** p<.01.
*** p<.001.
Note: Bowel urgency remission is 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.
Fatigue Numeric Rating Scale
As early as week 2, patients who received mirikizumab had significantly greater reductions from baseline in the fatigue Numeric Rating Scale compared with placebo (p<.05) (Change in Fatigue Numeric Rating Scale in LUCENT-1).2,3
Figure 10 description: The least-squares mean change from baseline in fatigue Numeric Rating Scale was significantly greater in the mirikizumab group than in the placebo group at weeks 2 (p<.05), 4 (p<.001), 8 (p<.001), and 12 (p<.001). At week 12, the least-squares mean reduction from baseline in fatigue Numeric Rating Scale was 1.96 for mirikizumab and 1.29 for placebo.
Abbreviations: IV = intravenous; LSM = least-squares mean; MIRI = mirikizumab; MMRM = mixed model for repeated measures; PBO = placebo.
* p<.05.
*** p<.001.
Abdominal Pain Improvement
As early as week 4, a significantly greater proportion of patients who received mirikizumab achieved abdominal pain improvement than did patients who received placebo (p<.01) (Abdominal Pain Improvement in LUCENT-1).2,3
Figure 11 description: The proportion of patients who achieved abdominal pain improvement was significantly higher in the mirikizumab group than in the placebo group at weeks 4 (p<.01), 8 (p<.001) and 12 (p<.001). At week 12, 66.4% of patients in the mirikizumab group and 49.2% of patients in the placebo group had achieved abdominal pain improvement.
Abbreviations: IV = intravenous; MIRI = mirikizumab; NRI = nonresponder imputation; PBO = placebo.
** p<.01.
*** p<.001.
Note: Improvement in abdominal pain is defined as an improvement ≥30% from induction baseline in patients with a baseline abdominal pain Numeric Rating Scale ≥3.
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).
1D'Haens G, Kobayashi T, Morris N, et al. Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-1 study. J Crohns Colitis. 2022;16(suppl 1):i028-i029. European Crohn's and Colitis Organisation abstract OP26. https://doi.org/10.1093/ecco-jcc/jjab232.025
2Danese 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.
3Danese 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. Poster presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
4Dignass 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.
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
Symptom Control Endpoint Definitions
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 response |
Reduction ≥30% from baseline in the sum of stool frequency and rectal bleeding subscores. |
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. |
Bowel urgency CMI |
Improvement ≥3 points in the Urgency NRS in patients with a baseline Urgency NRS ≥3. |
Improvement in abdominal pain |
Improvement ≥30% from induction baseline in patients with a baseline abdominal pain NRS ≥3. |
Abbreviation: CMI = Clinically Meaningful Improvement; NRS = Numeric Rating Scale.
Patient-Reported Outcomes Scales
Patient-reported outcomes assessed in the daily patient eDiary included the... |
which ranges in scores from... |
to... |
stool frequency Mayo subscore |
0 (normal number of stools/day for the patient) |
4 (≥5 stools/day more than normal for the patient). |
rectal bleeding Mayo subscore |
0 (no blood) |
3 (blood alone passed). |
bowel urgency severity NRS |
0 (no urgency) |
10 (worst possible urgency). |
abdominal pain NRS |
0 (none) |
10 (worst possible pain). |
fatigue NRS |
0 (none) |
10 (worst possible fatigue). |
Abbreviation: NRS = Numeric Rating Scale.
Note: Patient-reported outcomes were recorded daily in the patient eDiary then averaged by week. For stool frequency and rectal bleeding, weekly assessments were calculated by averaging the 3 most recent available diary days in a 7-day period. For bowel urgency, abdominal pain, and fatigue, all available diary days in a 7-day period were averaged.
Date of Last Review: October 11, 2022