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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.
What were the results of the phase 3 clinical trials of mirikizumab for the treatment of ulcerative colitis in adults?
In LUCENT-1, mirikizumab met all primary and key secondary endpoints. In LUCENT-2, the primary and all secondary endpoints were met in patients who responded to mirikizumab induction therapy and received maintenance treatment with mirikizumab.
Phase 3 Studies of Mirikizumab in Patients With Ulcerative Colitis
Phase 3 Clinical Trial Program of Mirikizumab for the Treatment of Ulcerative Colitis
The safety and efficacy of mirikizumab, a p19-directed anti-IL-23 antibody, in adult patients with moderate-to-severe active ulcerative colitis are being evaluated in the phase 3 studies LUCENT-1, LUCENT-2, and LUCENT-3 (Phase 3 Mirikizumab Clinical Studies in Patients With Moderate-to-Severe Active Ulcerative Colitis).1
|
LUCENT 1, AMAN |
LUCENT 2, AMBG |
LUCENT 3, AMAP |
|
Disease state |
Moderate-to-severe active UC |
Moderate-to-severe active UC |
Moderate-to-severe active UC |
Study design |
Randomized, double-blind, parallel, PBO-controlled induction |
Randomized, double-blind, parallel-arm, PBO-controlled maintenance |
Open-label extension |
Enrollment |
1160 adult patientsa |
1044 adult patientsa |
960 adult patientsa |
Treatments |
MIRI, PBO |
MIRI, PBO |
MIRI |
Ages eligible |
18-80 years |
18-80 years |
18-80 years |
Primary outcome |
Week 12: clinical remission by MMS |
Week 40: clinical remission by MMS |
Week 52: clinical remission by MMS |
Secondary outcomes |
Week 12: clinical response by MMS, endoscopic remission by MMS ES, symptomatic remission by MMS SF and RB, symptomatic response by MMS SF and RB, histologic remission, endoscopic response by MMS ES, symptoms by NRS, IBDQ, fecal calprotectin Weeks 0, 4, 8, and 12: PK |
Week 40: endoscopic remission by MMS ES, histologic remission, symptomatic remission by MMS SF and RB, endoscopic response by MMS ES, clinical response by MMS, IBDQ, fecal calprotectin, symptoms by NRS, hospitalizations Weeks 0, 4, 12, 24, and 40: PK |
Week 52: endoscopic remission by MMS ES, CS-free remission, histologic-endoscopic mucosal remission, IBDQ, symptoms by NRS, hospitalizations, UC surgeries including colectomy |
Abbreviations: CS = corticosteroid; ES = endoscopic subscore; IBDQ = Inflammatory Bowel Disease Questionnaire; MIRI = mirikizumab; MMS = Modified Mayo score; NRS = numeric rating score; PBO = placebo; PK = pharmacokinetics; RB = rectal bleeding; SF = stool frequency; UC = ulcerative colitis.
aEstimated enrollment.
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.2
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.2
Outcomes
The primary outcome was the proportion of patients in each treatment group who achieved clinical remission at week 12, defined as
- stool frequency subscore of 0 or 1 with ≥1-point decrease from baseline
- rectal bleeding subscore of 0, and
- endoscopic subscore of 0 or 1 excluding friability.2
Key Secondary Outcomes in the Phase 3 LUCENT-1 Clinical Trial lists the key secondary outcomes at week 12.
Outcome |
Definition |
Clinical response |
|
Endoscopic remission |
|
Symptomatic remission |
|
Clinical response in biologic-failed patients |
|
Histologic-endoscopic mucosal improvement (HEMI) |
|
Improvement in bowel urgency |
|
Baseline Characteristics
Baseline demographics and disease characteristics were similar across treatment groups (Baseline Demographics and Disease Characteristics in the Phase 3 LUCENT-1 Clinical Trial).2
Parameter |
MIRI 300 mg (N=868) |
PBO (N=294) |
Age, mean years (SD) |
42.9 (13.9) |
41.3 (13.8) |
Male, n (%) |
530 (61.1) |
165 (56.1) |
Weight, mean kg (SD) |
72.6 (17.3) |
70.9 (16.7) |
Disease duration, mean years (SD) |
7.2 (6.7) |
6.9 (7.0) |
Disease extent, n (%) |
||
Left-sided colitis |
544 (62.7) |
188 (64.2) |
Pancolitis |
318 (36.6) |
103 (35.2) |
Modified Mayo score category, n (%) |
||
Moderate (4-6) |
404 (46.5) |
138 (47.1) |
Severe (7-9) |
463 (53.3) |
155 (52.9) |
Mayo endoscopic subscore of 3 (severe disease), n (%) |
574 (66.1) |
200 (68.3) |
Bowel urgency severity,a median (Q1, Q3) |
6.0 (5.0, 8.0) |
7.0 (5.0, 8.0) |
Fecal calprotectin, median μg/g (Q1, Q3) |
1559.0 (634.0, 3210.0) |
1471.5 (626.5, 2944.5) |
C-reactive protein, median mg/L (Q1, Q3) |
4.1 (1.5, 9.6) |
4.2 (1.2, 9.5) |
Abbreviations: MIRI = mirikizumab; NRS = numeric rating scale; PBO = placebo; Q = quartile.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the electronic clinical outcome assessment (eCOA transcription) error in Poland and Turkey.
aThe Urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).
See Baseline and Prior Ulcerative Colitis Therapy in the Phase 3 LUCENT-1 Clinical Trial for data on prior and baseline treatment of ulcerative colitis for each treatment arm.
Parameter |
MIRI 300 mg (N=868) |
PBO (N=294) |
Prior ulcerative colitis treatment, n (%) |
||
Failed treatment with a biologic or tofacitinib |
361 (41.6) |
118 (40.1) |
Failed TNF inhibitor treatmenta |
325 (37.4) |
97 (33.0) |
Failed vedolizumab treatment |
159 (18.3) |
59 (20.1) |
Failed tofacitinib treatment |
34 (3.9) |
6 (2.0) |
Number of failed biologic or tofacitinib therapies |
||
0 |
507 (58.4) |
176 (59.9) |
1 |
180 (20.7) |
65 (22.1) |
2 |
154 (17.7) |
49 (16.7) |
>2 |
27 (3.1) |
4 (1.4) |
Ulcerative colitis therapy at baseline, n (%) |
||
Corticosteroids |
351 (40.4) |
113 (38.4) |
Immunomodulators |
211 (24.3) |
69 (23.5) |
Abbreviations: MIRI = mirikizumab; PBO = placebo; TNF = tumor necrosis factor.
Note: Data are from the modified intent-to-treat population which excludes patients impacted by the electronic clinical outcome assessment (eCOA transcription) error in Poland and Turkey.
aAny failure with anti-TNF therapy regardless of other biologic use.
Efficacy Results
Clinical Remission
Clinical remission at week 12 was achieved by
- 24.2% of patients who received mirikizumab, and
- 13.3% of patients who received placebo (p=.00006) (Clinical Remission at Week 12 in the Phase 3 LUCENT-1 Clinical Trial).3
Among subgroups of patients who were biologic-naïve, clinical remission at week 12 was achieved by
- 30.9% of patients who received mirikizumab, and
- 15.8% of patients who received placebo (p<.001) (Clinical Remission at Week 12 in the Phase 3 LUCENT-1 Clinical Trial).3
Among subgroups of patients who had previously failed a biologic or tofacitinib, clinical remission at week 12 was achieved by
- 15.2% of patients who received mirikizumab, and
- 8.5% of patients who received placebo (Clinical Remission at Week 12 in the Phase 3 LUCENT-1 Clinical Trial).3
Figure 1 description: Clinical remission at week 12 was achieved by 24.2% of patients who received mirikizumab and 13.3% of patients who received placebo (p=.00006). Among subgroups of patients who were biologic-naïve, clinical remission at week 12 was achieved by 30.9% of patients who received mirikizumab and 15.8% of patients who received placebo (p<.001). Among subgroups of patients who had previously failed a biologic or tofacitinib, clinical remission at week 12 was achieved by 15.2% of patients who received mirikizumab and 8.5% of patients who received placebo.
Abbreviations: IV = intravenous; PBO = placebo.
Notes: Biologic naïve/failed included tofacitinib naïve/failed patients. A total of 5 patients in the placebo group and 15 patients in the mirikizumab group were exposed to but did not fail treatment with biologics or tofacitinib.
The Cochran-Mantel-Haenszel (CMH) test was used to compare the treatment groups while adjusting for the stratification factors. A multiplicity adjusted p value of .00125 was considered significant.
Subgroup analyses by biologic-failed status in the right panel were not multiplicity controlled. A nominal p value of .05 was considered significant.
Δ indicates common risk difference vs placebo.
Secondary Outcomes
Clinical Response
Compared with placebo, a significantly greater proportion of patients who received mirikizumab achieved clinical response at week 12 (p<.00001) (Clinical Response at Week 12 in the Phase 3 LUCENT-1 Clinical Trial).3
Figure 2 description: Clinical response at week 12 was achieved by 63.5% of patients who received mirikizumab and 42.2% of patients who received placebo (p<.00001). Among subgroups of patients who were biologic-naïve, clinical response at week 12 was achieved by 70.1% of patients who received mirikizumab and 50.3% of patients who received placebo (p<.001). Among subgroups of patients who had previously failed a biologic or tofacitinib, clinical response at week 12 was achieved by 54.6% of patients who received mirikizumab and 29.7% of patients who received placebo (p<.001).
Abbreviations: IV = intravenous; PBO = placebo.
Notes: Biologic naïve/failed included tofacitinib naïve/failed patients. A total of 5 patients in the placebo group and 15 patients in the mirikizumab group were exposed to but did not fail treatment with biologics or tofacitinib.
The Cochran-Mantel-Haenszel (CMH) test was used to compare the treatment groups while adjusting for the stratification factors. A multiplicity adjusted p value of .00125 was considered significant.
Clinical response at week 12 in patients who had previously failed a biologic or tofacitinib is multiplicity controlled.
Δ indicates common risk difference vs placebo.
Endoscopic and Histologic Endpoints
A significantly greater proportion of patients who received mirikizumab achieved endoscopic remission and histologic improvement than did patients who received placebo (p<.00001 for both endpoints) (Endoscopic and Histologic Endpoints at Week 12 in the Phase 3 LUCENT-1 Clinical Trial).3
Figure 3 description: Endoscopic remission at week 12 was achieved by 36.3% of patients who received mirikizumab and 21.1% of patients who received placebo (p<.00001). Histologic-endoscopic mucosal improvement at week 12 was achieved by 27.1% of patients who received mirikizumab and 13.9% of patients who received placebo (p<.00001).
Abbreviations: IV = intravenous; PBO = placebo.
Notes: The Cochran-Mantel-Haenszel (CMH) test was used to compare the treatment groups while adjusting for the stratification factors. A multiplicity adjusted p value of .00125 was considered significant. Δ indicates common risk difference vs placebo.
Symptomatic Endpoints
Compared with placebo, a significantly greater proportion of patients who received mirikizumab reached symptomatic remission as early as week 4 and at each week thereafter through week 12 (p<.001 for each timepoint) (Symptomatic Remission and Change From Baseline in Bowel Urgency at Week 12 in the Phase 3 LUCENT-1 Clinical Trial).3
The least-squares mean change from baseline in bowel urgency numeric rating scale was significantly greater in the mirikizumab group than in the placebo group at weeks 4 (p<.001), 8 (p<.00001), and 12 (p<.00001) (Symptomatic Remission and Change From Baseline in Bowel Urgency at Week 12 in the Phase 3 LUCENT-1 Clinical Trial).3
Figure 4 description: Compared with placebo, a significantly greater proportion of patients who received mirikizumab reached symptomatic remission as early as week 4 and at each week thereafter through week 12 (p<.001 for each timepoint). The least-squares mean change from baseline in bowel urgency numeric rating scale was significantly greater in the mirikizumab group than in the placebo group at weeks 4 (p<.001), 8 (p<.00001), and 12 (p<.00001).
Abbreviations: BL = baseline; LSM = least-squares mean; MMRM = mixed model for repeated measures; NRS = numeric rating scale; PBO = placebo.
Notes: The Cochran-Mantel-Haenszel (CMH) test was used to compare the treatment groups for symptomatic remission while adjusting for the stratification factors. Symptomatic remission at weeks 4 and 12 were prespecified as multiplicity-controlled endpoints where a p value of .00125 was considered significant. MMRM was used to compare the treatment groups for bowel movement urgency improvement. Week 12 for bowel movement urgency improvement was prespecified as a multiplicity-controlled endpoint where a multiplicity adjusted p value of .00125 was considered significant. Weeks 2, 4, and 8 for bowel movement urgency improvement was not prespecified as multiplicity controlled and a nominal p value of .05 was considered significant.
Safety Results
The frequencies of treatment-emergent adverse events were similar among patients who received mirikizumab (44.5%) and patients who received placebo (46.1%). Fewer patients who received mirikizumab than placebo experienced serious adverse events or discontinued from the study due to adverse events. There were no deaths in either treatment arm. Safety Outcomes in the 12-Week Phase 3 LUCENT-1 Clinical Trial lists additional safety data.2
Parametersa |
MIRI 300 mg (N=958) |
PBO (N=321) |
TEAEs |
426 (44.5) |
148 (46.1) |
SAEs |
27 (2.8) |
17 (5.3) |
Discontinuations due to AE |
15 (1.6) |
23 (7.2) |
TEAEs occurring in ≥3% of patients in any treatment group |
||
Nasopharyngitis |
39 (4.1) |
10 (3.1) |
Anemia |
32 (3.3) |
19 (5.9) |
Headache |
32 (3.3) |
9 (2.8) |
Ulcerative colitis |
17 (1.8) |
24 (7.5) |
AEs of special interest |
||
All infections |
145 (15.1) |
45 (14.0) |
Serious infections |
7 (0.7) |
2 (0.6) |
Opportunistic infections |
5 (0.5) |
1 (0.3) |
Cerebrocardiovascular eventsb |
1 (0.1) |
2 (0.6) |
Malignanciesc |
2 (0.2) |
0 |
Depressiond |
4 (0.4) |
2 (0.6) |
Hepatic |
15 (1.6) |
5 (1.6) |
Immediate hypersensitivitiese |
10 (1.0) |
1 (0.3) |
Infusion reactions |
4 (0.4) |
1 (0.3) |
Abbreviations: AE = adverse event; MIRI = mirikizumab; PBO = placebo; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
aData are presented as n (%).
bThere were no reports of major adverse cardiac events in either arm.
cBoth were colon malignancies.
dThere were no reports of suicide or self-injury.
eOccurring within 24 hours of drug administration or on the day of drug administration if the time is missing.
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 moderate-to-severe ulcerative colitis who completed the LUCENT-1 study.4
Mirikizumab Responders in LUCENT-1
Treatment Assignment
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).4
Outcomes
The primary outcome was the achievement of clinical remission at week 40 among patients who achieved clinical response with mirikizumab during the 12-week induction period.4
Key secondary objectives were multiplicity controlled and included
- corticosteroid-free remission
- endoscopic remission
- histologic-endoscopic mucosal remission (HEMR)
- improvement in bowel urgency
- bowel urgency remission, and
- maintenance of clinical remission.4
Baseline Characteristics
Baseline demographics and disease characteristics were similar across treatment groups (Baseline Demographics and Disease Characteristics in the Phase 3 LUCENT-2 Clinical Trial).4
Parameter, n (%) |
MIRI 200 mg SC (N=365) |
PBO SC (N=179) |
Age, mean years (SD) |
43.4 (14.2) |
41.2 (12.8) |
Male, n (%) |
214 (58.6) |
104 (58.1) |
Disease duration, mean years (SD) |
6.9 (7.1) |
6.7 (5.6) |
Bowel Urgency severity,b median (Q1, Q3) |
6.0 (5.0, 8.0) |
6.0 (5.0, 8.0) |
Abbreviations: MIRI = mirikizumab; NRS = Numeric Rating Scale; PBO = placebo; Q = quartile; SC = subcutaneous.
aRefers to induction baseline (week 0 of LUCENT-1).
bThe Urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).
Baseline corticosteroid use was reported by 37% of patients who were rerandomized to mirikizumab and 38% of patients who were rerandomized to placebo in LUCENT-2.4
Prior biologic failure was reported by 35.1% of patients who were rerandomized to mirikizumab and 35.8% of patients who were rerandomized to placebo in LUCENT-2.4
Baseline and Prior Ulcerative Colitis Therapy in the Phase 3 LUCENT-2 Clinical Trial lists baseline and prior ulcerative colitis of mirikizumab induction responders in the LUCENT-2 clinical trial.
Parameter, n (%) |
MIRI 200 mg SC (N=365) |
PBO SC (N=179) |
Baseline corticosteroid use |
135 (37.0) |
68 (38.0) |
Baseline immunomodulator use |
78 (21.4) |
39 (21.8) |
Failed treatment with a biologic or tofacitinib |
128 (35.1) |
64 (35.8) |
Failed TNF inhibitor treatment |
112 (30.7) |
58 (32.4) |
Failed vedolizumab treatment |
47 (12.9) |
23 (12.8) |
Failed tofacitinib treatment |
8 (2.2) |
8 (4.5) |
Abbreviations: MIRI = mirikizumab; PBO = placebo; SC = subcutaneous; TNF = tumor necrosis factor.
aRefers to induction baseline (week 0 of LUCENT-1).
Efficacy Results
Clinical remission at week 40 was achieved by
- 49.9% of patients who were rerandomized to mirikizumab, and
- 25.1% of patients who were rerandomized to placebo (p<.001) (Efficacy Results in Mirikizumab Induction Responders With Moderate-to-Severe Ulcerative Colitis at the End of the 40-Week Maintenance Period in the Phase 3 LUCENT-2 Clinical Trial, mITT Population).4
Of the patients who received mirikizumab during the induction and maintenance treatment period and achieved clinical remission at the end of week 52 of LUCENT-2, 97.8% of those patients were in corticosteroid-free remission, defined as clinical remission at week 40, symptomatic remission at week 28, and no corticosteroid use for at least 12 weeks prior to week 4 (Efficacy Results in Mirikizumab Induction Responders With Moderate-to-Severe Ulcerative Colitis at the End of the 40-Week Maintenance Period in the Phase 3 LUCENT-2 Clinical Trial, mITT Population).5
In addition, patients who received mirikizumab achieved all key secondary endpoints at week 40 (p<.001) (Efficacy Results in Mirikizumab Induction Responders With Moderate-to-Severe Ulcerative Colitis at the End of the 40-Week Maintenance Period in the Phase 3 LUCENT-2 Clinical Trial, mITT Population).4
|
MIRI Induction Respondersb |
|
MIRI 200 mg SC (N=365) |
PBO SC (N=179) |
|
Clinical remission, n (%)c |
182 (49.9)d |
45 (25.1) |
Common risk differencee for MIRI vs placebo (95% CI) |
23.2 (15.2, 31.2) |
|
Corticosteroid-free clinical remission, n (%)f |
164 (44.9)d |
39 (21.8) |
Common risk difference for MIRI vs placebo (95% CI) |
21.3 (13.5, 29.1) |
|
Endoscopic remission, n (%)g |
214 (58.6)d |
52 (29.1) |
Common risk difference for MIRI vs placebo (95% CI) |
28.5 (20.2, 36.8) |
|
HEMR, n (%)h |
158 (43.3)d |
39 (21.8) |
Common risk difference for MIRI vs placebo (95% CI) |
19.9 (12.1, 27.6) |
|
Bowel urgency improvement, LSM (SE)i |
-3.80 (0.14)d |
-2.74 (0.20) |
LSM difference for MIRI vs placebo (SE) |
-1.06 (0.23) |
|
Bowel urgency remission, n/N (%)j |
144/336 (42.9)d |
43/172 (25.0) |
Common risk difference for MIRI vs placebo (95% CI) |
18.1 (9.8, 26.4) |
|
Maintenance of clinical remission, n/N (%)k |
91/143 (63.6)d |
24/65 (36.9) |
Common risk difference for MIRI vs placebo (95% CI) |
24.8 (10.4, 39.2) |
|
Abbreviations: eCOA = electronic clinical outcomes assessment; HEMR = histologic endoscopic mucosal remission; LSM = least squares mean; MIRI = mirikizumab; mITT = modified intent-to-treat; NRS = numeric rating scale; PBO = placebo; SC = subcutaneous.
aThe mITT population comprised all assigned/randomized patients who received any amount of study treatment excluding patients impacted by the eCOA transcription error in Poland and Turkey.
bDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the Rectal Bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
cDefined as 1) Stool Frequency=0 or SF=1 with a ≥1-point decrease from baseline, 2) Rectal Bleeding=0, and 3) Endoscopic Subscore=0 or 1 (excluding friability).
dp<.001 vs placebo.
eThe common risk difference is the difference in proportions adjusted for the stratification factors (biologic failure status, baseline corticosteroid use, geographic region, and induction remission status).
fDefined as 1) clinical remission at week 40, 2) symptomatic remission at week 28, and 3) no corticosteroid use for ≥12 weeks prior to week 40.
gDefined as Endoscopic Subscore=0 or 1 (excluding friability).
hHistologic remission with absence of mucosal neutrophils, defined using the Geboes scoring system with subscores of 0 for grades: 2b (lamina propria neutrophils); 3 (neutrophils in epithelium); 4 (crypt destruction); 5 (erosion or ulceration), and endoscopic remission.
iChange from induction baseline in Urgency NRS. The Urgency NRS is a patient-reported measure of the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).
jDefined 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.
kDefined as clinical remission at week 40 among patients induced into clinical remission with mirikizumab in LUCENT-1.
Change From Baseline in Bowel Urgency Through Week 40 in the Phase 3 LUCENT-2 Clinical Trial shows the change from baseline in the bowel urgency numeric rating scale through week 40 of LUCENT-2.
Figure 5 description: The least-squares mean change from baseline in bowel urgency numeric rating scale was significantly greater in the mirikizumab group than in the placebo group as early as week 12 (p<.05) and at each timepoint through week 40 (p≤.001).
Abbreviations: BL = baseline; LSM = least-squares mean; MMRM = mixed model for repeated measures; NRS = numeric rating scale; PBO = placebo; SC = subcutaneous.
Notes: The Cochran-Mantel-Haenszel (CMH) test was used to compare the treatment groups for urgency remission. MMRM was used to compare the treatment groups for bowel movement urgency improvement.
The proportion of patients who achieved clinical remission and endoscopic remission at the end of the 40-week maintenance period of LUCENT-2 was significantly greater in the mirikizumab group than in the placebo group regardless of prior biologic or tofacitinib use or failure (p<.001) (Efficacy Results in Mirikizumab Induction Responders With Moderate-to-Severe Ulcerative Colitis at the End of the 40-Week Maintenance Period in the Phase 3 LUCENT-2 Clinical Trial by Prior Biologic or Tofacitinib Use and Failure).5
Parameters, % |
MIRI Induction Respondersa |
|||
Biologic- or Tofacitinib-Naïve |
Failed Biologic or Tofacitinib |
|||
MIRI 200 mg SC |
PBO |
MIRI 200 mg SC |
PBO |
|
Clinical remissionb |
51.5c |
30.7 |
46.1c |
15.6 |
Common risk difference for MIRI vs placebo (95% CI) |
20.8 (10.2, 31.5) |
30.5 (18.1, 42.9) |
||
Endoscopic remissiond |
62.4c |
34.2 |
50.8c |
20.3 |
Common risk difference for MIRI vs placebo (95% CI) |
28.2 (17.5, 39.0) |
30.5 (17.3, 43.6) |
||
Abbreviations: MIRI = mirikizumab; PBO = placebo; SC = subcutaneous.
aDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the Rectal Bleeding subscore from baseline or a rectal bleeding score of 0 or 1.
bDefined as 1) Stool Frequency=0 or SF=1 with a ≥1-point decrease from baseline, 2) Rectal Bleeding=0, and 3) Endoscopic Subscore=0 or 1 (excluding friability).
cp<.001 vs placebo.
dDefined as Endoscopic Subscore=0 or 1 (excluding friability).
Safety Results
The frequency of treatment-emergent adverse events was similar between patients who received mirikizumab and patients who received placebo. In addition, fewer patients who received mirikizumab experienced a serious adverse event or discontinued from the study due to an adverse event than did patients who received placebo. See Safety Outcomes in Mirikizumab Induction Responders During the 40-Week Phase 3 LUCENT-2 Maintenance Study for additional safety data.4
Parameters |
MIRI Induction Respondersa |
|
MIRI 200 mg SC (N=389) |
PBO SC (N=192) |
|
TEAE, n (%) |
251 (64.5) |
132 (68.8) |
SAE, n (%) |
13 (3.3) |
15 (7.8) |
Most commonly reported TEAEs, n (%)b |
||
Nasopharyngitis |
28 (7.2) |
11 (5.7) |
Arthralgia |
26 (6.7) |
8 (4.2) |
Ulcerative colitis |
26 (6.7) |
40 (20.8) |
Injection-site pain |
17 (4.4) |
6 (3.1) |
Headache |
16 (4.1) |
2 (1.0) |
Rash |
14 (3.6) |
0 |
Pyrexia |
13 (3.3) |
5 (2.6) |
Anemia |
8 (2.1) |
9 (4.7) |
AEs of special interest |
||
All infections |
93 (23.9) |
44 (22.9) |
Serious infections |
3 (0.8) |
3 (1.6) |
Opportunistic infections |
5 (1.3)c |
0 |
Cerebrocardiovascular events |
0 |
1 (0.5)d |
Malignancies |
1 (0.3)e |
1 (0.5)f |
Depressiong |
4 (1.0) |
0 |
Suicide/self-injury |
1 (0.3)h |
0 |
Hepatic |
12 (3.1) |
4 (2.1) |
Immediate hypersensitivitiesi |
7 (1.8) |
2 (1.0) |
Injection-site reactions |
34 (8.7) |
8 (4.2) |
Death, n (%) |
0 |
1 (0.5)j |
Discontinuation due to AE, n (%) |
6 (1.5) |
16 (8.3) |
Abbreviations: AE = adverse event; MIRI = mirikizumab; PBO = placebo; SAE = serious adverse event; SC = subcutaneous; TEAE = treatment-emergent adverse event.
Note: Includes the safety population which is composed of all assigned/randomized patients who received any amount of study treatment.
aDefined as patients who received 12-week mirikizumab induction therapy and achieved 1) a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and 2) a decrease of ≥1 point in the Rectal Bleeding subscore from baseline or a Rectal Bleeding score of 0 or 1.
bDefined as adverse events reported by at least 3% of patients in either treatment group.
cFour cases of herpes zoster infections and 1 case of oral candidiasis; herpes zoster was severe in 1 patient.
dOne adjudicated event of ischemic stroke.
eGastric cancer.
fBasal cell carcinoma.
gExcluding suicide or self-injury.
hAttempted suicide not considered related to study drug by investigator.
iOccurring within 24 hours of drug administration or on the day of drug administration when time is missing.
jDue to COVID-19 infection.
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1US National Library of Medicine. ClinicalTrials.gov. February 29, 2000. Accessed August 20, 2021. https://clinicaltrials.gov/
2D'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
3D'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. Poster presented at: 17th Congress of the European Crohn’s and Colitis Organisation (ECCO Virtual); February 16-19, 2022.
4Dubinsky 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.
5Dubinsky 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. Poster presented at: Digestive Disease Week; May 24, 2022; San Diego, California.
Date of Last Review: May 24, 2022