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Omvoh ® (mirikizumab-mrkz) injection
300 mg/15 mL, 100 mg/mL
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What were the efficacy results in the phase 3 clinical trial of Omvoh® (mirikizumab-mrkz) for the treatment of Crohn's disease in adults?
A significantly greater proportion of patients in the mirikizumab group compared with the placebo group achieved both coprimary endpoints in the VIVID-1 study (p<.0001).
Content Overview
Design of the VIVID-1 Phase 3 Study of Mirikizumab for the Treatment of Crohn's Disease
- Key Inclusion and Exclusion Criteria for Participant Selection
- Treatment Regimens for Mirikizumab, Ustekinumab, and Placebo Among Randomized Groups
- Primary and Secondary Objectives Evaluating Efficacy of Mirikizumab Compared With Placebo or With Ustekinumab
Summary of Baseline Demographics and Clinical Characteristics Across Treatment Groups
- Efficacy of Mirikizumab Compared With Placebo in the VIVID-1 Study Primary Analysis Set
- Efficacy of Mirikizumab Compared With Ustekinumab in the VIVID-1 Study
- Efficacy of Ustekinumab Compared With Placebo in the VIVID-1 Study
- Comparative Changes in Biomarkers From Baseline Through Week 52 Among Mirikizumab, Ustekinumab, and Placebo Groups
- Histologic and Endoscopic-Histologic Response Among the Mirikizumab, Ustekinumab, and Placebo Treatment Groups
Design of the VIVID-1 Phase 3 Study of Mirikizumab for the Treatment of Crohn's Disease
VIVID-1 was a 52-week, phase 3, multicenter, randomized, double-blind, double-dummy, active- and placebo-controlled, treat-through study in patients with moderately to severely active Crohn's disease.1
Key Inclusion and Exclusion Criteria for Participant Selection
Key Inclusion Criteria
To be eligible for the study, participants had to
- be aged 18 to 80 years
- have a diagnosis of Crohn's disease or fistulizing Crohn's disease for at least 3 months prior to study enrollment
- have moderately to severely active Crohn's disease, defined as
- an unweighted baseline daily average loose stool frequency (SF) of at least 4, and/or
- an unweighted baseline daily average abdominal pain (AP) of at least 2
- have a Simple Endoscopic Score for Crohn's disease (SES-CD) of at least 7 in patients with ileal-colonic disease or at least 4 in patients with isolated ileal disease within 21 days before randomization, and
- have had an inadequate response, loss of response, or intolerance to at least 1 conventional corticosteroid, immunomodulator, or approved biologic therapy for Crohn's disease.1
During the early stages of enrollment, the protocol was amended to permit the inclusion of a specific group of patients with an SES-CD of ≥3 to <7 for colonic or ileal-colonic disease, or SES-CD <4 for individuals with isolated ileal disease. These patients were randomly assigned and included in the study for exploratory analyses. While they were included in safety analyses, they were not considered part of the primary population for efficacy analyses.1
Key Exclusion Criteria
Patients who had previously received anti-interleukin-23 antibodies, except for no more than 2 doses of ustekinumab and had not failed or had an intolerance to ustekinumab, were excluded from the study.1
Treatment Regimens for Mirikizumab, Ustekinumab, and Placebo Among Randomized Groups
In this treat-through study, a total of 1152 patients were randomized 6:3:2 to either
- mirikizumab 900 mg infused intravenously (IV) every 4 weeks for 3 doses followed by 300 mg injected subcutaneously (SC) every 4 weeks through week 52
- ustekinumab 6 mg/kg infused IV for one dose followed by 90 mg injected SC every 8 weeks through week 52, or
- placebo.1
From weeks 8 through 20, all patients received their assigned treatment and matching placebo via both intravenous infusion and subcutaneous injection.1
Randomization was stratified by
- biologic-failed status (yes or no)
- baseline corticosteroid use (yes or no)
- baseline SES-CD total score (<12 or ≥12)
- region (North America, Europe, or other), and
- combined stratification factor using either
- baseline SF≥7 and/or
- baseline AP score ≥2.5 (yes or no).1
Treatment Protocol for Patients Randomized to Placebo Based on Response at Week 12
Patients randomized to placebo received an intravenous infusion every 4 weeks for 3 doses. At week 12, patients were classified as responders if they had achieved at least a 30% decrease in loose SF and/or AP, with neither score higher than baseline. Accordingly,
- placebo responders received another 3 doses of placebo infused IV every 4 weeks for 3 doses followed by placebo injected SC every 4 weeks through week 52, and
- placebo nonresponders received mirikizumab 900 mg infused IV every 4 weeks for 3 doses followed by 300 mg injected SC every 4 weeks through week 52.1
Primary and Secondary Objectives Evaluating Efficacy of Mirikizumab Compared With Placebo or With Ustekinumab
Corresponding endpoints and their definitions for the objectives below are defined in Primary and Major Secondary Endpoints in the VIVID-1 Clinical Trial in the Appendix.
Coprimary Efficacy Objectives
The primary objective of the VIVID-1 study was to evaluate the superiority of the efficacy of mirikizumab to placebo in patients with moderately to severely active Crohn's disease as assessed by
- clinical response by patient-reported outcomes (PRO) at week 12 and endoscopic response at week 52, and
- clinical response by PRO at week 12 and clinical remission by Crohn's Disease Activity Index (CDAI) at week 52.1
Major Secondary Objectives
The major secondary objectives of the VIVID -1 study, which evaluated the superiority of the efficacy of mirikizumab to placebo in patients with moderately to severely active Crohn's disease, were multiplicity controlled and assessed by
- endoscopic response at week 12
- clinical remission by CDAI at week 12
- clinical response by PRO at week 12
- endoscopic remission at week 12
- Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores at week 12
- endoscopic response at week 52
- clinical remission by CDAI at week 52, and
- clinical response by PRO at week 12 and
- clinical remission by PRO at week 52
- corticosteroid-free clinical remission by CDAI at week 52, and
- endoscopic remission at week 52.1
Additional multiplicity adjusted secondary objectives at week 52 were to assess the
- superiority of mirikizumab to ustekinumab in achieving endoscopic response, and
- noninferiority of mirikizumab to ustekinumab in achieving clinical remission by CDAI.1
Scoring Methodology for Endoscopic Evaluations
Endoscopies were video-recorded and scored by 2 blinded central readers independently. If a discrepancy in scoring occurred between the first 2 readers, a third central reader was added. The final score was the mean of all readers' scores.1
Summary of Baseline Demographics and Clinical Characteristics Across Treatment Groups
Baseline Demographics
Baseline demographics were similar across treatment groups (Baseline Demographics Across Treatment Groups in the Primary Analysis Set of VIVID-1).1
|
Mirikizumab (n=579) |
Ustekinumab (n=287) |
Placebo (n=199) |
Age, mean (SD), y |
36.0 (13.2) |
36.6 (12.7) |
36.3 (12.7) |
Male, n (%) |
332 (57.3) |
137 (47.7) |
118 (59.3) |
Weight, mean (SD), kg |
68.02 (18.3) |
66.86 (17.6) |
69.55 (19.0) |
BMI, mean (SD) |
23.2 (5.4) |
23.3 (5.5) |
23.8 (5.8) |
Underweight (<18.5 kg/m2) |
109 (18.8) |
52 (18.1) |
38 (19.1) |
Normal (≥18.5 and <25 kg/m2) |
289 (49.9) |
141 (49.1) |
94 (47.2) |
Overweight (≥25 and <30 kg/m2) |
115 (19.9) |
62 (21.6) |
31 (15.6) |
Obese (≥30 and <40 kg/m2) |
60 (10.4) |
27 (9.4) |
34 (17.1) |
Race, n (%) |
|||
White |
408 (71.5) |
201 (70.3) |
144 (74.6) |
Black or African American |
10 (1.8) |
8 (2.8) |
5 (2.6) |
Asian |
148 (25.9) |
74 (25.9) |
42 (21.8) |
American Indian or Alaska Native |
2 (0.4) |
2 (0.7) |
2 (1.0) |
Multiple |
3 (0.5) |
1 (0.3) |
0 (0.0) |
Geographic region, n (%) |
|||
North America |
77 (13.3) |
37 (12.9) |
27 (13.6) |
Europe and rest of world |
319 (55.1) |
155 (54.0) |
117 (58.8) |
Central America or South America |
30 (5.2) |
20 (7.0) |
9 (4.5) |
Asia |
153 (26.4) |
75 (26.1) |
46 (23.1) |
Abbreviations: BMI = body mass index; SES-CD = Simple Endoscopic Score for Crohn's disease.
aThe primary analysis set is comprised of those participants who received ≥1 dose of study drug and had a baseline SES-CD ≥7 (or ≥4 for isolated ileal disease).
Baseline Disease Characteristics
Baseline disease characteristics were similar across treatment groups (Baseline Disease Characteristics Across Treatment Groups in the Primary Analysis Set of the VIVID-1 Study).1
The mean (SD) duration of Crohn's disease across treatment groups was 7.4 (7.9) years (Baseline Disease Characteristics Across Treatment Groups in the Primary Analysis Set of the VIVID-1 Study).1
|
Mirikizumab (n=579) |
Ustekinumab (n=287) |
Placebo (n=199) |
Duration of Crohn's disease mean (SD), y |
7.4 (8.2) |
7.2 (7.7) |
7.8 (7.4) |
CDAI, mean (SD) |
323.1 (85.8) |
318.5 (93.2) |
318.9 (86.2) |
SF daily average, mean (SD) |
5.7 (3.0) |
5.7 (2.9) |
5.8 (3.2) |
AP daily average, mean (SD) |
2.1 (0.6) |
2.1 (0.6) |
2.1 (0.6) |
SES-CD total score, mean (SD) |
13.5 (6.6) |
13.9 (6.6) |
13.1 (6.0) |
CRP, mean (IQR), mg/L |
8.5 (2.9-25.0) |
8.9 (3.4-24.8) |
7.6 (2.9-18.8) |
FCal, mean (IQR), mg/kg |
1315.0 (444.0-2676.0) |
1489.0 (519.0-2814.0) |
1161.0 (324.0-2170.0) |
Disease location, n (%) |
|||
Ileum only |
65 (11.2) |
29 (10.1) |
19 (9.5) |
Colon only |
225 (38.9) |
120 (41.8) |
77 (38.7) |
Ileum and colon |
289 (49.9) |
138 (48.1) |
103 (51.8) |
Abbreviations: AP = abdominal pain; CDAI = Crohn's Disease Activity Index; CRP = C-reactive protein; FCal = fecal calprotectin; IQR = interquartile range; SES-CD = Simple Endoscopic Score for Crohn's disease; SF = stool frequency.
aThe primary analysis set is comprised of those participants who received ≥1 dose of study drug and had a baseline SES-CD ≥7 (or ≥4 for isolated ileal disease).
Baseline and Prior Medication Use
Baseline and prior use of medications for the treatment of Crohn's disease were similar across treatment groups (Baseline and Prior Medication Use Across Treatment Groups in the Primary Analysis Set of the VIVID-1 Study).1
Approximately half of the patients in each treatment group had failed at least one biologic, and the proportion of patients who had failed more than one biologic was
- 18.3% of patients in the mirikizumab group
- 16.7% of patients in the ustekinumab group, and
- 15.6% of patients in the placebo group.1
Treatmentb |
Mirikizumab (n=579) |
Ustekinumab (n=287) |
Placebo (n=199) |
Baseline treatment use |
|||
Corticosteroid use |
177 (30.6) |
90 (31.4) |
58 (29.1) |
Prednisone equivalent dose, median (range), mg |
20 (3-30) |
16 (5-100) |
15 (5-30) |
Budesonide use |
63 (10.9) |
27 (9.4) |
23 (11.6) |
Immunomodulator use |
146 (25.2) |
87 (30.3) |
58 (29.1) |
Prior treatment use |
|||
Prior ustekinumab use |
4 (0.7) |
1 (0.3) |
2 (1.0) |
Prior anti-TNF failure |
265 (45.8) |
133 (46.3) |
89 (44.7) |
Prior anti-integrin failure |
68 (11.7) |
31 (10.8) |
24 (12.1) |
Prior biologic failure |
281 (48.5) |
139 (48.4) |
97 (48.7) |
Number of failed biologics |
|||
0 |
298 (51.5) |
148 (51.6) |
102 (51.3) |
1 |
175 (30.2) |
91 (31.7) |
66 (33.2) |
2 |
82 (14.2) |
42 (14.6) |
25 (12.6) |
>2 |
24 (4.1) |
6 (2.1) |
6 (3.0) |
Abbreviations: SES-CD = Simple Endoscopic Score for Crohn's disease; TNF = tumor necrosis factor.
aIncludes the 1065 patients who qualified for the primary analysis set, meaning the patients received at least one dose of study drug and had a baseline SES-CD ≥7 (or ≥4 for isolated ileal disease).
bData presented as n (%) unless otherwise indicated.
Comparative Efficacy Analyses of Mirikizumab, Ustekinumab, and Placebo in the VIVID-1 Phase 3 Study of Mirikizumab for the Treatment of Crohn's Disease
Efficacy of Mirikizumab Compared With Placebo in the VIVID-1 Study Primary Analysis Set
A total of 1150 patients who were randomized in the VIVID-1 study received at least one dose of study drug, of which 1065 had a baseline SES-CD of at least 7 (or ≥4 for isolated ileal disease) and represented the efficacy population.1
A total of 80 patients (40.2%) originally randomized to placebo did not achieve PRO clinical response at week 12 and were switched to blinded mirikizumab treatment.1
Week 12 and Week 52 Coprimary Composite Efficacy Endpoints of Mirikizumab Versus Placebo
Both of the coprimary endpoints were met (Comparative Efficacy of Mirikizumab Versus Placebo on Coprimary Endpoints By Biologic Failure Status in Patients With Moderately to Severely Active Crohn's Disease: VIVID-1 Study Results, NRI).1
The week 52 endoscopic response composite was achieved by
- 38.0% of patients in the mirikizumab treatment group, and
- 9.0% of patients in the placebo treatment group (p<.0001).1
The week 52 CDAI clinical remission composite was achieved by
- 45.4% of patients in the mirikizumab treatment group, and
- 19.6% of patients in the placebo treatment group (p<.0001).1
The significant differences between the mirikizumab and placebo treatment groups were observed with and without prior biologic failure.1
Endpointa |
Mirikizumab (n=579) |
Placebo (n=199) |
Difference vs Placebo |
Week 12 PRO clinical responseb and week 52 endoscopic responsec |
220/579 (38.0) |
18/199 (9.0) |
28.7 (20.6-36.8)d |
Not biologic failed |
117/298 (39.3) |
12/102 (11.8) |
27.5 (19.1-35.9)d |
Biologic failed |
103/281 (36.7) |
6/97 (6.2) |
30.5 (23.1-37.9)d |
Week 12 PRO clinical responseb and week 52 CDAI clinical remissione |
263/579 (45.4) |
39/199 (19.6) |
25.8 (15.9-35.6)d |
Not biologic failed |
141/298 (47.3) |
27/102 (26.5) |
20.8 (10.6-31.1)f |
Biologic failed |
122/281 (43.4) |
12/97 (12.4) |
31.0 (22.3-39.8)d |
Abbreviations: AP = abdominal pain; CDAI = Crohn's Disease Activity Index; NRI = nonresponder imputation; PRO = patient-reported outcome; SES-CD = Simple Endoscopic Score for Crohn's disease; SF = stool frequency.
aTreatment group data presented as n/N (%). Difference vs placebo presented as adjusted risk difference (99.5% CI) for all participants and unadjusted risk difference (95% CI) for subgroups.
bDefined as ≥30% decrease in SF and/or AP score, with neither score worse than baseline.
cDefined as ≥50% reduction from baseline in SES-CD total score.
dp<.0001.
eDefined as CDAI total score <150.
fp<.01.
Major Secondary Endpoints of Mirikizumab Versus Placebo
Week 12 and Week 52 Composite Endpoints
A significantly greater proportion of patients who received mirikizumab compared with those who received placebo achieved all of the week 12 and week 52 composite endpoints at week 12, which included
- endoscopic remission-composite (mirikizumab, 23.5%; placebo, 4.0%; p<.0001), and
- corticosteroid-free clinical remission composite (mirikizumab, 43.7%; placebo, 18.6%; p<.0001).1
Comparative Efficacy of Mirikizumab Versus Placebo on Secondary Composite Endpoints By Biologic Failure Status in Patients With Moderately to Severely Active Crohn's Disease: VIVID-1 Study Results, NRI presents additional data for these endpoints stratified by biologic failed status.
Endpointa |
Mirikizumab (n=579) |
Placebo (n=199) |
Unadjusted Risk Difference, Mirikizumab Vs Placebo |
Week 12 PRO clinical responseb and week 52 PRO clinical remissionc |
263/579 (45.4) |
39/199 (19.6) |
25.7 (15.9-35.6)d |
Not biologic failed |
141/298 (47.3) |
28/102 (27.5) |
19.9 (9.5-30.2)e |
Biologic failed |
122/281 (43.4) |
11/97 (11.3) |
32.1 (23.5-40.6)d |
Week 12 PRO clinical responseb and CS-free from week 40 to week 52 and CDAI clinical remissionf at week 52 |
253/579 (43.7) |
37/199 (18.6) |
25.0 (15.2-34.7)d |
Not biologic failed |
139/298 (46.6) |
25/102 (24.5) |
22.1 (12.0-32.2)d |
Biologic failed |
114/281 (40.6) |
12/97 (12.4) |
28.2 (19.5-36.9)d |
Week 12 PRO clinical responseb and week 52 endoscopic remissiong |
92/579 (15.9) |
4/199 (2.0) |
13.8 (8.7-18.9)d |
Not biologic failed |
55/298 (18.5) |
3/102 (2.9) |
15.5 (10.0-21.0)d |
Biologic failed |
37/281 (13.2) |
1/97 (1.0) |
12.1 (7.7-16.6)d |
Week 12 PRO clinical responseb and week 52 endoscopic remission (conventional)h |
136/579 (23.5) |
8/199 (4.0) |
19.4 (13.1-25.7)d |
Not biologic failed |
82/298 (27.5) |
6/102 (5.9) |
21.6 (14.8-28.5)d |
Biologic failed |
54/281 (19.2) |
2/97 (2.1) |
17.2 (11.7-22.6)d |
Abbreviations: AP = abdominal pain; CDAI = Crohn's Disease Activity Index; CS = corticosteroid; NRI = nonresponder imputation; PRO = patient-reported outcome; SES-CD = Simple Endoscopic Score for Crohn's disease; SF = stool frequency.
aTreatment group data presented as n/N (%). Difference vs placebo presented as adjusted risk difference (99.5% CI) for all participants and unadjusted risk difference (95% CI) for subgroups.
bDefined as ≥30% decrease in SF and/or AP score, with neither score worse than baseline.
cDefined as SF ≤3 and not worse than baseline (per Bristol Stool Scale Category 6 or 7) and AP score <1 and no worse than baseline.
dp<.0001.
ep<.01.
fDefined as CDAI total score <150.
gDefined as SES-CD ≤4 and at least a 2-point reduction versus baseline and no subscore >1 (subscore representing segmental subscore), as scored by 2 independent central reviewers.
hDefined as SES-CD ≤4 and at least a 2-point reduction versus baseline and no subscore >1 in any individual variable (nonmultiplicity controlled), as scored by 2 independent central reviewers.
Week 12
A significantly greater proportion of patients who received mirikizumab compared with those who received placebo achieved all of the major secondary endpoints at week 12. These endpoints included
- endoscopic response (mirikizumab, 32.5%; placebo, 12.6%; p<.0001)
- clinical remission by CDAI (mirikizumab, 37.7%; placebo, 25.1%; p=.0014)
- clinical response by PRO (mirikizumab, 70.6%; placebo, 51.8%; p<.0001), and
- endoscopic remission (mirikizumab, 10.9%; placebo, 4.0%; p=.0034).1
Week 12 Comparative Efficacy of Mirikizumab Versus Placebo on Secondary Endpoints By Biologic Failure Status in Patients With Moderately to Severely Active Crohn's Disease: VIVID-1 Study Results, NRI presents additional data for these endpoints stratified by biologic failed status.
Endpointa |
Mirikizumab (n=579) |
Placebo (n=199) |
Difference Vs Placebo |
Endoscopic responseb |
188/579 (32.5) |
25/199 (12.6) |
19.7 (11.1-28.2)c |
Not biologic failed |
113/298 (37.9) |
17/102 (16.7) |
21.3 (12.2-30.3)c |
Biologic failed |
75/281 (26.7) |
8/97 (8.2) |
18.4 (10.9-26.0)c |
CDAI clinical remissiond |
218/579 (37.7) |
50/199 (25.1) |
12.4 (2.2-22.7)e |
Not biologic failed |
118/298 (39.6) |
26/102 (25.5) |
14.1 (4.0-24.2)f |
Biologic failed |
100/281 (35.6) |
24/97 (24.7) |
10.8 (0.6-21.1) |
PRO clinical responseg |
409/579 (70.6) |
103/199 (51.8) |
18.9 (7.5-30.3)c |
Not biologic failed |
205/298 (68.8) |
59/102 (57.8) |
10.9 (0.0-21.9)h |
Biologic failed |
204/281 (72.6) |
44/97 (45.4) |
27.2 (16.0-38.4)c |
Endoscopic remissioni |
63/579 (10.9) |
8/199 (4.0) |
6.8 (1.6-12.1)j |
Not biologic failed |
43/298 (14.4) |
6/102 (5.9) |
8.5 (2.5-14.6)h |
Biologic failed |
20/281 (7.1) |
2/97 (2.1) |
5.1 (0.9-9.2) |
Endoscopic remission (conventional)k |
102/579 (17.6) |
14/199 (7.0) |
10.6 (4.1-17.2)l |
Not biologic failed |
65/298 (21.8) |
12/102 (11.8) |
10.0 (2.2-17.9)h |
Biologic failed |
37/281 (13.2) |
2/97 (2.1) |
11.1 (6.2-16.0)f |
Abbreviations: AP = abdominal pain; CDAI = Crohn's Disease Activity Index; FACIT-F = Functional Assessment of Chronic Illness Therapy-Fatigue; LSM = least squares mean; NRI = nonresponder imputation; NRS = Numeric Rating Score; PRO = patient-reported outcome; SES-CD = Simple Endoscopic Score for Crohn's disease; SF = stool frequency.
aTreatment group data presented as n/N (%). Difference vs placebo presented as adjusted risk difference (99.5% CI) for all participants and unadjusted risk difference (95% CI) for subgroups.
bDefined as ≥50% reduction from baseline in SES-CD total score.
cp<.0001.
dDefined as CDAI total score <150.
ep=.0014.
fp<.01.
gDefined as ≥30% decrease in SF and/or AP score, with neither score worse than baseline.
hp<.05.
iDefined as SES-CD ≤4 and at least a 2-point reduction versus baseline and no subscore >1 (subscore representing segmental subscore), as scored by 2 independent central reviewers.
jp=.0034.
kDefined as SES-CD ≤4 and at least a 2-point reduction versus baseline and no subscore >1 in any individual variable (nonmultiplicity controlled), as scored by 2 independent central reviewers.
lp=.0002.
Week 52
A significantly greater proportion of patients who received mirikizumab compared with those who received placebo achieved the major secondary endpoints at week 52. These endpoints included
- endoscopic response (mirikizumab, 48.4%; placebo, 9.0%; p<.0001), and
- clinical remission by CDAI (mirikizumab, 54.1%; placebo, 19.6%; p<.0001).1
Week 52 Comparative Efficacy of Mirikizumab Versus Placebo on Secondary Endpoints By Biologic Failure Status in Patients With Moderately to Severely Active Crohn's Disease: VIVID-1 Study Results presents additional data for these endpoints stratified by biologic failed status.
Endpointa |
Mirikizumab (n=579) |
Placebo (n=199) |
Difference Vs Placebo |
Endoscopic responseb |
280/579 (48.4) |
18/199 (9.0) |
39.1 (31.0-47.2)c |
Not biologic failed |
154/298 (51.7) |
12/102 (11.8) |
39.9 (31.5-48.4)c |
Biologic failed |
126/281 (44.8) |
6/97 (6.2) |
38.7 (31.1-46.2)c |
CDAI clinical remissiond |
313/579 (54.1) |
39/199 (19.6) |
34.6 (24.7-44.4)c |
Not biologic failed |
169/298 (56.7) |
27/102 (26.5) |
30.2 (20.0-40.5)c |
Biologic failed |
144/281 (51.2) |
12/97 (12.4) |
38.9 (30.1-47.7)c |
Abbreviations: CDAI = Crohn's Disease Activity Index; SES-CD = Simple Endoscopic Score for Crohn's disease.
aTreatment group data presented as n/N (%). Difference vs placebo presented as adjusted risk difference (99.5% CI) for all participants and unadjusted risk difference (95% CI) for subgroups. The treat-through result reflects the week 52 endpoint regardless of response status at week 12.
bDefined as ≥50% reduction from baseline in SES-CD total score.
cp<.0001.
dDefined as CDAI total score <150.
Improvements in Patient-Reported Outcomes and Quality of Life Among the Mirikizumab and Placebo Treatment Groups
Improvement in Fatigue
Fatigue, as measured by FACIT-F, was significantly improved from baseline in the mirikizumab group compared with the placebo group at week 12 (p<.0001). The significant improvement from baseline to week 12 in FACIT-F for the mirikizumab group compared with the placebo group was demonstrated in patients who had and had not previously failed a biologic (Change From Baseline to Week 12 in FACIT-F With Mirikizumab Compared With Placebo by Biologic Failed Status in Patients With Moderately to Severely Active Crohn's Disease: VIVID-1 Study Results).1
Endpointa |
Mirikizumab (n=579) |
Placebo (n=199) |
Difference Vs Placebo |
Change from baseline in FACIT-F |
5.9 (0.4) |
2.6 (0.6) |
3.2 (1.2-5.2)b |
Not biologic failed |
6.69 (0.511) |
3.96 (0.863) |
2.72 (0.8-4.7)c |
Biologic failed |
5.04 (0.504) |
1.21 (0.854) |
3.83 (1.9-5.8)b |
Abbreviations: FACIT-F = Functional Assessment of Chronic Illness Therapy-Fatigue; LSM = least squares mean.
aData presented as LSM (SE). Difference vs placebo presented as adjusted risk difference (99.5% CI) for all participants and unadjusted risk difference (95% CI) for subgroups.
bp<.0001.
cp<.01.
Efficacy of Mirikizumab Compared With Ustekinumab in the VIVID-1 Study
Mirikizumab was noninferior to ustekinumab for CDAI clinical remission. At week 52, CDAI clinical remission was achieved by
- 54.1% of patients who received mirikizumab, and
- 48.4% of patients who received ustekinumab (Efficacy of Mirikizumab Compared With Ustekinumab at Week 52 in Patients With Moderately to Severely Active Crohn's Disease in the VIVID-1 Study).1
Mirikizumab was not superior to ustekinumab for endoscopic response. At week 52, endoscopic response was achieved by
- 48.4% of patients who received mirikizumab, and
- 46.3% of patients who received ustekinumab (Efficacy of Mirikizumab Compared With Ustekinumab at Week 52 in Patients With Moderately to Severely Active Crohn's Disease in the VIVID-1 Study).1
Mirikizumab was superior to ustekinumab in achieving the composite of CDAI clinical remission and endoscopic response (p<.05) at week 52 (Efficacy of Mirikizumab Compared With Ustekinumab at Week 52 in Patients With Moderately to Severely Active Crohn's Disease in the VIVID-1 Study).3
The proportions of patients who achieved CDAI corticosteroid-free clinical remission and endoscopic remission were similar between the mirikizumab and ustekinumab treatment groups (Efficacy of Mirikizumab Compared With Ustekinumab at Week 52 in Patients With Moderately to Severely Active Crohn's Disease in the VIVID-1 Study).1
Compared with ustekinumab, although not significant, a greater proportion of patients in the mirikizumab group who had previously failed a biologic for the treatment of Crohn's disease achieved CDAI clinical remission and endoscopic response (Efficacy of Mirikizumab Compared With Ustekinumab at Week 52 in Patients With Moderately to Severely Active Crohn's Disease in the VIVID-1 Study).1
Mirikizumab |
Ustekinumab |
|
CDAI clinical remissionc |
313/579 (54.1)d |
139/287 (48.4) |
Not biologic failed |
169/298 (56.7) |
81/148 (54.7) |
Biologic failed |
144/281 (51.2) |
58/139 (41.7) |
Endoscopic responsee |
280/579 (48.4) |
133/287 (46.3) |
Not biologic failed |
154/298 (51.7) |
78/148 (52.7) |
Biologic failed |
126/281 (44.8) |
55/139 (39.6) |
CS-free CDAI remissionc |
300/579 (51.8) |
131/287 (45.6) |
Not biologic failed |
164/298 (55.0) |
76/148 (51.4) |
Biologic failed |
136/281 (48.4) |
55/139 (39.6) |
Endoscopic remission SES-CD ≤4f |
165/579 (28.5) |
80/287 (27.9) |
Composite of clinical remission by CDAIc and endoscopic responsee |
199/579 (34.4)g |
80/287 (27.9) |
Abbreviations: CDAI = Crohn's Disease Activity Index; CS = corticosteroid; SES-CD = Simple Endoscopic Score for Crohn's disease.
aData presented as n/N (%).
bThe efficacy analyses for mirikizumab compared with ustekinumab included the multiplicity-adjusted secondary endpoints at week 52 of clinical remission by CDAI (noninferiority test with 10% margin) and endoscopic response (superiority test), and the nonmultiplicity-adjusted secondary endpoints at week 52 of endoscopic remission, CS-free CDAI remission, and the composite of CDAI clinical remission and endoscopic response. Missing data were imputed as nonresponse. Patients who switched to mirikizumab were subsequently treated as nonresponders.
cDefined as CDAI total score <150.
dNoninferiority met after accounting for multiplicity.
eDefined as ≥50% reduction from baseline in SES-CD total score.
fDefined as SES-CD total score ≤4 and ≥2-point reduction from baseline, and no subscore >1.
gp<.05 vs ustekinumab.
Efficacy of Ustekinumab Compared With Placebo in the VIVID-1 Study
Comparison of Secondary Endpoints for Ustekinumab Compared With Placebo presents data on secondary endpoints for ustekinumab versus placebo for week 12 and week 52 composite endpoints.
Endpointa |
Ustekinumab (n=287) |
Placebo (n=199) |
Difference Ustekinumab Vs Placebo (95% CI) |
Week 12 PRO clinical responseb and week 52 endoscopic responsec |
107 (37.3) |
18 (9.0) |
27.8 (21.0-34.6)d |
Week 12 PRO clinical responseb and week 52 CDAI clinical remissione |
117 (40.8) |
39 (19.6) |
21.0 (13.1-28.8)d |
Abbreviations: AP = abdominal pain; CDAI = Crohn's Disease Activity Index; PRO = patient-reported outcome; SES-CD = Simple Endoscopic Score for Crohn's disease; SF = stool frequency.
aData presented as n (%).
bDefined as ≥30% decrease in SF and/or AP score, with neither score worse than baseline.
cDefined as ≥50% reduction from baseline in SES-CD total score.
dp<.0001.
eDefined as CDAI total score <150.
Comparative Changes in Biomarkers From Baseline Through Week 52 Among Mirikizumab, Ustekinumab, and Placebo Groups
The least squares mean (LSM) change from baseline in fecal calprotectin was significantly greater in the mirikizumab group compared with
- the placebo group as early as week 4 (p<.001) and was sustained through week 52 (p<.001), and
- the ustekinumab group at weeks 28 (p<.05), 44 (p<.01), and 52 (p<.001).1
The LSM change from baseline in C-reactive protein (CRP) was significantly greater in the mirikizumab group compared with
- the placebo group as early as week 4 (p<.001) and was sustained through week 52 (p<.001), and
- the ustekinumab group at weeks 16 (p<.01), 44 (p<.01), and 52 (p<.05).1
Change From Baseline in Fecal Calprotectin and C-Reactive Protein at Weeks 12 and 52 Among Mirikizumab, Ustekinumab, and Placebo Groups in the VIVID-1 Clinical Trial shows the change from baseline in fecal calprotectin and CRP at weeks 12 and 52 among mirikizumab, ustekinumab, and placebo groups in the VIVID-1 clinical trial.
Endpointa |
Mirikizumab (n=579) |
Ustekinumab (n=287) |
Placebo (n=199) |
Change from baseline in FCP |
|||
12 weeks |
-1.05 |
-0.94 |
-0.09b |
52 weeks |
-1.41 |
-0.96b |
-0.19b |
Change from baseline in CRP |
|||
12 weeks |
-0.73 |
-0.69 |
0.12b |
52 weeks |
-0.93 |
-0.75c |
-0.08b |
Abbreviations: CRP = C-reactive protein; FCP = fecal calprotectin; LSM = least squares mean.
aData presented as LSM (SE). For participants in the placebo group who switched to mirikizumab at week 12, the baseline values were carried forward to derive the change from baseline at week 52.
bp<.001 vs mirikizumab.
cp<.05 vs mirikizumab.
Histologic and Endoscopic-Histologic Response Among the Mirikizumab, Ustekinumab, and Placebo Treatment Groups
At week 52, a significantly greater proportion of patients who received mirikizumab compared with those who received ustekinumab (p<.01) or placebo (p<.001) achieved histologic response, defined as a ≥50% reduction from baseline in the sum of 5 segments active Robarts Histopathology Index or active Global Histologic Disease Score (Histologic and Endoscopic-Histologic Response Among the Mirikizumab, Ustekinumab, and Placebo Treatment Groups in the VIVID-1 Study).4
Likewise, a significantly greater proportion of patients who received mirikizumab compared with those who received placebo (p<.001) achieved endoscopic-histologic response, while the response was similar between patients who received mirikizumab or ustekinumab (Histologic and Endoscopic-Histologic Response Among the Mirikizumab, Ustekinumab, and Placebo Treatment Groups in the VIVID-1 Study).4
Histologic response data stratified by biologic failed status are presented in Histologic and Endoscopic-Histologic Response Among the Mirikizumab, Ustekinumab, and Placebo Treatment Groups in the VIVID-1 Study.
Endpointb |
Mirikizumab |
Ustekinumab |
Placeboc |
Histologic response |
337/579 (58.2) |
140/287 (48.8)d |
32/199 (16.1)e |
Not biologic failed |
169/273 (61.9) |
74/130 (56.9) |
24/91 (26.4)e |
Biologic failed |
144/255 (56.5) |
52/126 (41.3)d |
6/88 (6.8)e |
Endoscopic-histologic response |
217/528 (41.1) |
88/256 (34.4) |
11/179 (6.1)e |
Not biologic failed |
116/273 (42.5) |
53/130 (40.8) |
10/91 (11.0)e |
Biologic failed |
101/255 (39.6) |
35/126 (27.8)f |
1/88 (1.1)e |
Abbreviations: GHAS = Global Histologic Disease Activity Score; NRI = nonresponder imputation; RHI = Robarts Histopathology Index.
aTo achieve histologic response, the sum of 5 segments active RHI or active GHAS needed to be reduced by ≥50% from baseline.
bData presented as n/N (%).
cNRI used for binary outcomes at week 52 for patients who switched to mirikizumab at week 12.
dp<.01 vs mirikizumab.
ep<.001 vs mirikizumab.
fp=.02 vs mirikizumab.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Ferrante M, D'Haens G, Jairath V, et al; VIVID Study Group. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn’s disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. Lancet. 2024;404(10470):2423-2436. https://doi.org/10.1016/S0140-6736(24)01762-8
2Jairath V, Sands BE, Bossuyt P, et al; VIVID Study Group. Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate to severe Crohn's disease: results from the phase 3 VIVID 1 study. J Crohns Colitis. 2024;18(suppl 1):i62-i64. European Crohn’s and Colitis Organisation abstract OP35. https://doi.org/10.1093/ecco-jcc/jjad212.0035
3Jairath V, Sands BE, Bossuyt P, et al. Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate-to-severe Crohn's disease: results from the phase 3 VIVID 1 study. Poster presented at: 19th Congress of the European Crohn’s and Colitis Organisation (ECCO); February 21-24, 2024; Stockholm, Sweden.
4D'Haens G, Danese S, Sands BE, et al. Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate-to-severe Crohn's disease: results from the phase 3 VIVID 1 study. Poster presented at: Digestive Disease Week; May 19-21, 2024; Washington, DC.
Appendix
Endpoint |
Definition |
Coprimary endpoints: mirikizumab vs placebo |
|
Proportion of participants achieving PRO clinical response at week 12 and endoscopic response at week 52 |
Clinical response by PRO: a ≥30% decrease in SF and/or AP score, with neither score worse than baseline; Endoscopic response: a ≥50% reduction from baseline in SES-CD total score |
Proportion of participants achieving PRO clinical response at week 12 and CDAI clinical remission at week 52. |
Clinical response by PRO: a ≥30% decrease in SF and/or AP score, with neither score worse than baseline; CDAI clinical remission: a CDAI total score <150 |
Major secondary endpoints: mirikizumab vs placebo |
|
Week 12 |
|
Proportion of patients achieving endoscopic response |
A ≥50% reduction from baseline in SES-CD total score |
Proportion of patients achieving endoscopic remission SES-CD ≤4 |
An SES-CD total score ≤4 and ≥2-point reduction from baseline, and no subscore >1 |
Proportion of patients achieving PRO clinical response |
A ≥30% decrease in SF and/or AP score, with neither score worse than baseline |
Proportion of participants achieving CDAI clinical remission |
A CDAI total score <150 |
Change from baseline in FACIT-F scores |
NA |
Week 52 |
|
Proportion of participants achieving endoscopic response |
A ≥50% reduction from baseline in SES-CD total score |
Proportion of patients achieving CDAI clinical remission |
A CDAI total score <150 |
Week 12 and week 52 composite |
|
Proportion of participants achieving PRO clinical response at week 12 and PRO clinical remission at week 52 |
Clinical response by PRO: a ≥30% decrease in SF and/or AP score, with neither score worse than baseline; Clinical remission by PRO: an SF ≤3 and not worse than baseline (per Bristol Stool Scale Category 6 or 7) and AP score <1 and no worse than baseline |
Proportion of participants achieving PRO clinical response at week 12 and endoscopic remission SES-CD ≤4 at week 52 |
Clinical response by PRO: a ≥30% decrease in SF and/or AP score, with neither score worse than baseline; Endoscopic remission SES-CD ≤4: an SES-CD total score ≤4 and ≥2-point reduction from baseline, and no subscore >1 |
Proportion of participants achieving PRO clinical response at week 12 and corticosteroid-free from week 40 to week 52, and CDAI clinical remission at week 52 |
Clinical response by PRO: a ≥30% decrease in SF and/or AP score, with neither score worse than baseline; CDAI clinical remission: a CDAI total score <150 |
Major secondary endpoints: mirikizumab vs ustekinumab |
|
Week 52 |
|
Proportion of participants achieving endoscopic response |
A ≥50% reduction from baseline in SES-CD total score |
Proportion of participants achieving CDAI clinical remission |
A CDAI total score <150 |
Abbreviations: AP = abdominal pain; CDAI = Crohn's Disease Activity Index; FACIT-F = Functional Assessment of Chronic Illness Therapy-Fatigue; PRO = patient-reported outcome; SES-CD = Simple Endoscopic Score for Crohn's disease; SF = stool frequency per Bristol Stool Scale Category 6 or 7.
Date of Last Review: December 04, 2024