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Mirikizumab
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How does mirikizumab affect quality of life and work productivity in patients with ulcerative colitis?
Patients who received mirikizumab had significantly greater improvements in work productivity and activity impairment and in IBDQ scores than did patients who received placebo.
LUCENT-1 and LUCENT-2 Study Designs
LUCENT-1
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
LUCENT-2
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-IL-23 antibody, conducted in adult patients with moderately-to-severely active ulcerative colitis who completed the LUCENT-1 study.2
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).2
Work Productivity and Activity Impairment Questionnaire
Work Productivity and Activity Impairment Questionnaire Ulcerative Colitis (WPAI:UC) scores ranging from 0% to 100%, with higher scores indicating higher levels of impairment, were calculated from patient-reported measurements. The overall activity impairment domain included all respondents, and the absenteeism, presenteeism, and work productivity domains included respondents who reported employment at the time of the analyses. At baseline, of 1162 patients, 705 (60.67%) reported employment.3
At week 12 of LUCENT-1, patients who received mirikizumab had significantly greater improvements from baseline in activity impairment (p<.001), absenteeism (p<.05), presenteeism (p<.01), and work productivity (p<.01) than did patients who received placebo (Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis Scores at Week 12 of LUCENT-1 and at Week 40 of LUCENT-2).3
Of the patients who received mirikizumab in LUCENT-1 and achieved a clinical response, those who continued treatment with mirikizumab had significantly greater improvements from induction baseline at week 40 of LUCENT-2 in activity impairment (p<.001), presenteeism (p<.001), and work productivity (p<.001) than did patients who received placebo (Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis Scores at Week 12 of LUCENT-1 and at Week 40 of LUCENT-2).3
Outcome |
LUCENT-1 |
LUCENT-2 (MIRI Induction Responders) |
||
MIRI 300 mg IV Q4W |
PBO IV Q4W |
MIRI 200 mg SC Q4W |
PBO SC Q4W |
|
Week 12 |
Week 40a |
|||
Activity impairment of all participants, LSM change from BL (SE) |
-20.90 (0.87) |
-12.90 (1.41) |
-32.46 (1.35) |
-22.91 (1.77) |
LSM differenceb (SE) |
-8.01 (1.57)c |
-9.55 (1.98)c |
||
Absenteeism from work of employed participants,d LSM change from BL (SE) |
-7.88 (1.03) |
-3.45 (1.75) |
-12.85 (1.28) |
-10.78 (1.68) |
LSM differenceb (SE) |
-4.43 (1.95)e |
-2.07 (1.93) |
||
Presenteeism at work of employed participants,d LSM change from BL (SE) |
-19.25 (1.03) |
-13.94 (1.75) |
-29.42 (1.51) |
-19.82 (1.98) |
LSM differenceb (SE) |
-5.31 (1.95)f |
-9.60 (2.28)c |
||
Overall work impairment of employed participants,d LSM change from BL (SE) |
-20.65 (1.16) |
-14.91 (1.99) |
-31.72 (1.73) |
-22.59 (2.26) |
LSM differenceb (SE) |
-5.74 (2.20)f |
-9.13 (2.61)c |
||
Abbreviations: BL = baseline; IV = intravenous; LSM = least-squares mean; MIRI = mirikizumab; PBO = placebo; Q4W = every 4 weeks; SC = subcutaneous; UC = ulcerative colitis; WPAI = Work Productivity and Activity Impairment Questionnaire.
Note: The changes from baseline at week 12 of LUCENT-1 and at week 40 of LUCENT-2 were evaluated by analysis of covariance, and stratification factors and baseline scores were used as covariates. Stratification for LUCENT-1 included baseline disease activity, and stratification for LUCENT-2 included the LUCENT-1 clinical remission status.
aOutcomes are change from induction baseline to week 40 of LUCENT-2, for a total of 52 weeks of continuous therapy.
bThe LSM difference is the LSM change from baseline in WPAI:UC scores of participants receiving mirikizumab minus the LSM change from baseline in WPAI:UC scores of participants receiving placebo.
cp<.001.
dAt baseline, 705 of 1162 (60.67%) patients reported employment.
ep<.05.
fp<.01.
Inflammatory Bowel Disease Questionnaire
The Inflammatory Bowel Disease Questionnaire (IBDQ) measures health-related quality of life, and higher scores indicate better quality of life.4
A minimal clinically important difference (MCID), or IBDQ response, was defined as an improvement from baseline of at least 16 points in the total IBDQ score, and IBDQ remission was defined as a total IBDQ score of at least 170 points.4
At week 12 of LUCENT-1 and at week 40 of LUCENT-2, patients who received mirikizumab had significantly greater improvements from baseline in the IBDQ total and domain scores than did patients who received placebo (p<.001 for all) (Change From Baseline in Inflammatory Bowel Disease Questionnaire Scores at Week 12 of LUCENT-1 and at Week 40 of LUCENT-2).4
Compared with placebo, a significantly greater proportion of patients who received mirikizumab achieved IBDQ response and IBDQ remission at week 12 of LUCENT-1 and at week 40 of LUCENT-2 (p<.001 for all) (Change From Baseline in Inflammatory Bowel Disease Questionnaire Scores at Week 12 of LUCENT-1 and at Week 40 of LUCENT-2).4
Outcome |
LUCENT-1 |
LUCENT-2 (MIRI Induction Responders) |
||
MIRI 300 mg IV Q4W |
PBO IV Q4W |
MIRI 200 mg SC Q4W |
PBO SC Q4W |
|
Week 12 |
Week 40a |
|||
IBDQ total score, LSM change from BL (SE) |
38.42 (1.11) |
25.21 (1.80) |
49.75 (2.10) |
24.51 (2.77) |
LSM difference (SE) |
13.21 (2.01)b |
25.24 (3.09)b |
||
IBDQ response,c n (%) |
631 (72.7) |
164 (55.8) |
289 (79.2) |
88 (49.2) |
Risk difference (95% CI) |
17.1 (10.7, 23.5)b |
29.5 (21.0, 37.9)b |
||
IBDQ remission,d n (%) |
499 (57.5) |
117 (39.8) |
264 (72.30) |
77 (43.00) |
Risk difference (95% CI) |
18.1 (11.8, 24.4)b |
28.5 (20.1, 37.0)b |
||
Abbreviations: BL = baseline; IBDQ = Inflammatory Bowel Disease Questionnaire; IV = intravenous; LSM = least-squares mean; MIRI = mirikizumab; PBO = placebo; Q4W = every 4 weeks; SC = subcutaneous.
Notes:
The IBDQ domains and total scores were evaluated by analysis of variance with modified baseline observation carried forward and adjustment for covariates.
The IBDQ-based measurements for clinical response and remission were analyzed using nonresponder imputation. The common risk difference was the stratification-adjusted difference in the proportion of patients receiving mirikizumab minus the proportion of patients receiving placebo. Stratification for LUCENT-1 included baseline disease activity, and stratification for LUCENT-2 included the LUCENT-1 clinical remission status.
aOutcomes are change from induction baseline to week 40 of LUCENT-2, for a total of 52 weeks of continuous therapy.
bp<.001.
cDefined as an improvement of at least 16 points in the total IBDQ score.
dDefined as a total IBDQ score of at least 170 points.
Additional Information
Additional safety and efficacy data from the mirikizumab ulcerative colitis registration studies are available in the following document:
References
The published reference below is 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
2Dubinsky 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.
3Sands BE, Feagan B, Gibble TH, et al. Mirikizumab improves Work Productivity and Activity Impairment Questionnaire scores in moderately to severely active ulcerative colitis: The LUCENT-1 and LUCENT-2 randomized, double-blind, placebo-controlled phase 3 induction and maintenance studies. Abstract presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
4Sands BE, Feagan B, Gibble TH, et al. Mirikizumab improves quality of life in moderately to severely active ulcerative colitis: improvement in Inflammatory Bowel Disease scores in participants of the LUCENT-1 and LUCENT-2 randomized, double-blind, placebo-controlled phase 3 induction and maintenance trials. Abstract presented at: United European Gastroenterology Week (UEGW); October 8-11, 2022.
Date of Last Review: October 11, 2022