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(ustekinumab)

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STELARA® (ustekinumab)

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STELARA - Comparison to Risankizumab in the Treatment of Adult Patients with Crohn's Disease - SEQUENCE Study

Last Updated: 01/21/2026

SUMMARY

  • Please refer to the local labeling for relevant information on STELARA.
  • SEQUENCE is a phase 3b, multicenter, randomized, head-to-head (study drug open-label and efficacy assessment blinded) study comparing the efficacy and safety of STELARA vs risankizumab (RZB) in adult patients with moderate-to-severe Crohn's disease (CD) who failed ≥1 prior anti-tumor necrosis factor (TNF) therapy.1 

CLINICAL DATA

Phase 3b SEQUENCE Study

Peyrin-Biroulet et al (2024)1 reported the efficacy and safety results from a phase 3b, multicenter, randomized, head-to-head, (study drug open-label and efficacy assessment blinded) study that compared STELARA vs RZB over a 48-week period in adult patients with moderate-to-severe CD who failed ≥1 prior anti-TNF therapy.

Study Design/Methods

SEQUENCE Study Design1

Abbreviations: APS, abdominal pain score; BL, baseline; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; IV, intravenous; q4w, every 4 weeks; q8w, every 8 weeks; R, randomization; RZB, risankizumab; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease; SF, stool frequency; TNF, tumor necrosis factor; UST, ustekinumab.
aExcluding the narrowing component confirmed by a central reader.
bWeight-based dosing: ≤55 kg, 260 mg; >55-85 kg, 390 kg; >85 kg, 520 mg.
cMandatory glucocorticoid tapering began at week 2.
dNoninferiority (10% margin) of RZB to UST assessed in first 50% of patients.
eSuperiority of RZB to UST.

Results

Patient Characteristics
  • The randomized study population included 527 patients (STELARA, n=265; RZB, n=262); with 7 patients excluded for receiving an incorrect RZB dose, the intention-to-treat population comprised 520 patients (STELARA, n=265; RZB, n=255).
  • A total of 193 of 265 (72.8%) patients in the STELARA group and 230 of 255 (90.2%) patients in the RZB group completed the treatment.
  • A total of 27.2% (n=72) of patients in the STELARA group and 9.8% (n=25) of patients in the RZB group discontinued the study drug prematurely. The mean time to discontinuation of STELARA vs RZB was 156.3 vs 182.6 days.
  • Baseline patient demographics and disease characteristics are presented in Table: Baseline Demographics and Disease Characteristics in the ITT Population.

Baseline Demographics and Disease Characteristics in the ITT Populationa,1 
Characteristic
STELARA
n=265
RZB
n=255
Age, mean (SD), years
38.3 (13.8)
38.0 (13.1)
Disease duration, median (range), years
7.3 (0.3-51.9)
7.3 (0.3-40.6)
SES-CD, median (IQR)
12.0 (8.0-19.0)
12.0 (8.0-18.0)
Immunomodulator useb, n (%)
47 (17.7)
34 (13.3)
Glucocorticoid use, n (%)
71 (26.8)
58 (22.7)
Baseline fecal calprotectinc, median (range), μg/g
1515 (30-26,361)
1030 (30-26,823)
Baseline hs-CRPd, median (range), mg/L
9.40 (0.2-196.6)
8.20 (0.2-287.1)
CDAIe, median (IQR)
307.8 (260.8-347.9)
306.0 (265.9-344.8)
Failed >1 anti-TNF therapies, n (%)
61 (23.0)
59 (23.1)
Abbreviations: CDAI, Crohn’s Disease Activity Index; hs-CRP, high-sensitivity C-reactive protein; IQR, interquartile range; ITT, intention-to-treat; IV, intravenous; RZB, risankizumab; SC, subcutaneous; SD, standard deviation; SES-CD, Simple Endoscopic Score for Crohn’s Disease; TNF, tumor necrosis factor.
aITT population included patients who were randomized to STELARA (weight-based IV induction dose followed by a SC maintenance dose of 90 mg) or RZB (600 mg IV induction dose, 360 mg SC maintenance dose) and received ≥1 dose of the study drug.
bImmunomodulators: thiopurines and methotrexate.
cThe normal value for fecal calprotectin is <50 µg per gram. The number of patients evaluated in the RZB group was 207 and the number of patients evaluated in the STELARA group was 215.
dSTELARA, n=257; RZB, n=246.
eSTELARA, n=263; RZB, n=251.
Efficacy
  • When comparing to STELARA, RZB demonstrated noninferiority for achieving clinical remission at week 24 and superiority for achieving endoscopic remission at week 48. The primary and secondary endpoints are summarized in Table: Summary of Efficacy Data in ITT Population.

Summary of Efficacy Data in ITT Populationa,1
Week 24
Week 48
STELARA
(N=265)
% (95% CI)b
RZB
(N=255)
% (95% CI)b
Adjusted Differencec
% (95% CI)
STELARA
(N=265)
% (95% CI)b
RZB
(N=255)
% (95% CI)b
Adjusted Differencec
% (95% CI)
Primary endpoints
   Clinical
   remissiond
39.5
(31.3-47.7)
58.6
(50.1-67.1)
18.4
(6.6-30.3)e
-
-
-
   Endoscopic
   remissionf
-
-
-
16.2
(11.8-20.7)
31.8
(26.1-37.5)
15.6
(8.4-22.9)g
Secondary endpoints
   Clinical
   remissionh
-
-
-
40.8
(34.8-46.7)
60.8
(54.8-66.8)
19.7
(11.3-28.1)g
   Endoscopic
   responsei
26.4
(21.1-31.7)
45.2
(39.1-51.3)
18.9
(10.9-26.9)g
21.9
(16.9-26.9)
45.1
(39.0-51.2)
23.3
(15.4-31.2)g
   Glucocorticoid-
   free endoscopic
   remissionf,j
-
-
-
15.5
(11.1-19.8)
31.4
(25.7-37.1)
15.9
(8.8-23.1)g
   Glucocorticoid-
   free clinical
   remissionh,j
-
-
-
40.4
(34.5-46.3)
60.8
(54.8-66.8)
20.1
(11.7-28.4)g
Abbreviations: CI, confidence interval; CDAI, Crohn’s Disease Activity Index; COVID-19, coronavirus disease 2019; ITT, intention-to-treat; IV, intravenous; RZB, risankizumab; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn's disease; TNF, tumor necrosis factor.
aUnless specified, all analyses were performed in the ITT population (patients who were randomized to receive STELARA or RZB 600 mg IV induction dose and 360 mg SC maintenance dose) and received ≥1 dose of the study drug.
bThe 95% CI for the percentage of patients with a response was based on the point estimate and standard error derived from multiple imputation according to Rubin’s rule if there are data that were missing due to COVID-19 or geopolitical conflict. The CI was based on the normal approximation to the binomial distribution if there are no data that were missing due to Covid-19 or geopolitical conflict.
cThe adjusted difference (RZB minus STELARA), the 95% CI for the adjusted difference, and the P-value were calculated according to the Cochran-Mantel-Haenszel test for common risk difference stratified according to the number of anti-TNF therapies that failed (1 or >1), and glucocorticoid use at baseline (yes or no).
dClinical remission (defined as a CDAI score of <150) was assessed in the first 50% of the ITT population to complete the visit at week 24 or withdraw from trial participation.
eNoninferiority was shown with respect to clinical remission at week 24 if the lower limit of the 95% CI of the adjusted difference between the STELARA and RZB groups was greater than the noninferiority margin of -10 percentage points.
fEndoscopic remission was defined as an SES-CD of ≤4, a decrease of at least 2 points from baseline, and no subscore of >1 in any individual variable.
gP<0.001.
hClinical remission at week 48 was assessed among 100% of the ITT population.
iEndoscopic response was defined as a decrease of >50% from baseline in the SES-CD (or a decrease of ≥2 points from baseline in patients with an SES-CD of 4 at baseline).
jGlucocorticoid-free was defined as not receiving glucocorticoids at the week 48 visit; glucocorticoid-free clinical remission at week 48 was assessed in 100% of the ITT population.
Safety
  • Among all patients who were randomized and received ≥1 dose of the study drug (safety analysis population), the overall incidence of treatment-emergent adverse events (AEs) was similar in the STELARA (82.6%) and RZB (85.1%) groups; see Table: Summary of AEs.
  • The summary of AEs of special interest is presented in Table: Summary of AEs of Special Interest.

Summary of AEs1
STELARA
RZB
n (%)
(n=265)
No. of Events (Events Per 100 PY)
PY=269.9
n (%)
(n=262)
No. of Events (Events Per 100 PY)
PY=257.6
Any AEs
219 (82.6)
763 (282.7)
223 (85.1)
879 (341.2)
AEs related to the study drug according to the investigatora
58 (21.9)
111 (41.1)
73 (27.9)
167 (64.8)
Severe AEs
51 (19.2)
82 (30.4)
42 (16.0)
60 (23.3)
Serious AEs
46 (17.4)
64 (23.7)
27 (10.3)
36 (14.0)
AEs leading to discontinuation of the study drug
13 (4.9)
14 (5.2)
10 (3.8)
10 (3.9)
Deaths
0
0
0
0
Abbreviations: AE, adverse event; CD, Crohn’s disease; PY, patient-years; RZB, risankizumab; SAE, serious adverse event.
aAs assessed by the investigator.

Summary of AEs of Special Interest1
STELARA
RZB
n (%)
(n=265)
No. of Events (Events Per 100 PY)
PY=269.9
n (%)
(n=262)
No. of Events (Events Per 100 PY)
PY=257.6
Adjudicated MACE/extended MACEa
1 (0.4)b
1 (0.4)b
0
0
Serious infection
11 (4.2)
14 (5.2)
8 (3.1)
10 (3.9)
Active tuberculosis
0
0
0
0
Opportunistic infection excluding TB and herpes zoster
0
0
1 (0.4)
1 (0.4)
Herpes zoster
1 (0.4)
1 (0.4)
1 (0.4)
1 (0.4)
Malignant tumor
1 (0.4)c
1 (0.4)c
1 (0.4)d
1 (0.4)d
Hypersensitivity
24 (9.1)
32 (11.9)
28 (10.7)
37 (14.4)
Serious hypersensitivity
0
0
0
0
Adjudicated anaphylactic reaction
0
0
0
0
Injection-site reaction
6 (2.3)
8 (3.0)
5 (1.9)
5 (1.9)
Abbreviations: AE, adverse event; MACE, major adverse cardiovascular events; PY, patient-years; RZB, risankizumab; TB, tuberculosis.
aMACE were defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. extended MACE was defined as MACE along with hospitalization for unstable angina and coronary revascularization procedures.
bOne patient reported one nonfatal myocardial infarction.
cMalignant tumor: anal squamous cell carcinoma.
dMalignant tumor: squamous cell carcinoma of skin.

Post Hoc Analysis

Irving et al (2025)2 conducted a post hoc analysis of the SEQUENCE study to evaluate the changes in total Simple Endoscopic Score (SES-CD) and individual SES-CD components (affected surface, ulcerated surface, size of ulcers, and presence of narrowing) from baseline to weeks 24 and 48.

Results
  • Evaluable endoscopy data were available for 461 patients (STELARA, n=223; RZB, n=238) and 379 patients (STELARA, n=169; RZB, n=210) at weeks 24 and 48, respectively.
  • At baseline, the total SES-CD was similar between the treatment groups.
    • At weeks 24 and 48, patients treated with RZB vs STELARA showed numerically greater improvements in total SES-CD (week 24, -6.6 vs -3.9; nominal P-value; week 48, -7.3 vs -4.8; nominal P-value).
    • At weeks 24 and 48, patients treated with RZB vs STELARA showed numerically greater improvements across all individual SES-CD components, including affected surface, ulcerated surface, and size of ulcers (nominal P-value).

Raine et al (2025)3 conducted a post hoc analysis of the SEQUENCE study to evaluate the corticosteroid (CS)-sparing effects of STELARA vs RZB over 48 weeks in patients taking CS at baseline.

Results
  • Of the 520 patients in the primary efficacy analysis, 71 from the STELARA group and 58 from the RZB group were taking CS as baseline. The mean daily prednisone-equivalent dose at baseline was 19.5 mg and 21.4 mg for STELARA and RZB, respectively.
  • For details on efficacy outcomes among patients taking CS at baseline, see Table: Efficacy Outcomes in Patients Taking CS at Baseline. By week 8, 75.9% vs 59.2% of patients in the RZB vs STELARA group discontinued CS. By week 24, similar proportion of patients in the RZB vs STELARA group discontinued CS. By week 48, 86.2% vs 57.7% of patients in the RZB vs STELARA group discontinued CS.

Efficacy Outcomes in Patients Taking CS at Baseline3
Week 24
Week 48
STELARA (n=71)
RZB
(n=58)
STELARA (n=71)
RZB
(n=58)
CS-free clinical remission, n (%)
24 (33.8)
26 (44.8)
22 (31.0)
33 (56.9)a
CS-free clinical remission and CS-free for 90 days, n (%)
N/A
N/A
22 (31.0)
32 (55.2)a
CS-free endoscopic remission, n (%)
8 (11.3)
20 (34.5)a
9 (12.7)
19 (32.8)a
CS-free endoscopic remission and CS-free for 90 days, n (%)
N/A
N/A
9 (12.7)
19 (32.8)a
Abbreviations: CDAI, Crohn’s Disease Activity Index; COVID-19, coronavirus disease 2019; CS, corticosteroid; N/A, not applicable; RZB, risankizumab; SES-CD, Simple Endoscopic Score for Crohn’s disease.
aNominal P-value. These endpoints were not adjusted for multiple comparisons and statistical significance has not been established.Note: Nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 and /or geographical conflict was used. CS-free clinical remission was indicated by CDAI <150 and without receiving CS at the corresponding visit. CS-free endoscopic remission was indicated by SES-CD <4- and ≥2-point reduction vs baseline and no subscore of >1 in any individual variable, as scored by the central reviewer, and without receiving CS at the corresponding visit.

Health-Related Quality of Life

Loftus et al (2025)4 evaluated the treatment effect of STELARA vs RZB with respect to achieving clinically meaningful within-person changes in patients with moderate to severe CD based on patient-reported outcomes (PROs) from the SEQUENCE study.

Results

Proportion of patients demonstrating clinically meaningful within-person changes with RZB vs STELARA at weeks 24 and 48 are as follows:

  • Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16 point increase in the total score)
    • At week 24: 75.3% vs 64.2%
    • At week 48: 68.6% vs 50.9%
  • IBDQ remission (total score ≥170 points)
    • At week 24: 52.5% vs 30.9%
    • At week 48: 49.8% vs 33.2%
  • Improvement in 36–item short–form health survey (SF–36) physical component score (PCS)
    • From baseline to week 24: 65.9% vs 53.2%
    • From baseline to week 48: 63.9% vs 46.0% STELARA (all comparisons P<0.01).
  • Improvement in SF-36 mental component score (MCS)
    • From baseline to week 48: 54.1% vs 40.0% (P<0.01 for all comparisons)
  • At baseline, a similar proportion of patients treated with RZB vs STELARA, reported fatigue (92.2% vs 92.8%), depression (66.7% vs 70.9%), anxiety (71.4% vs 75.5%), or bowel urgency (69.8% vs 73.2%) ‘all-some of the time’ on IBDQ.
  • At weeks 24 and 48, a significantly lower proportion of patients treated with RZB vs STELARA, reported fatigue (week 24, 51.4% vs 69.1%; week 48, 54.9% vs 72.1%; P<0.0001), depression (week 24, 34.1% vs 42.6%; P=0.05; week 48, 35.7% vs 58.1%; P<0.0001), anxiety (week 24, 34.1% vs 49.8%; P<0.001; week 48, 35.3% vs 58.5%; P<0.0001), or bowel urgency (week 24, 27.1% vs 40.0%; P<0.01; week 48, 27.1% vs 50.6%; P<0.0001) ‘all-some of the time’ on IBDQ.

LITERATURE SEARCH

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 21 September 2025.

 

References

Show
1 Peyrin-Biroulet L, Chapman JC, Colombel JF, et al. Risankizumab versus ustekinumab for moderate-to-severe Crohn’s disease. N Engl J Med. 2024;391(3):213-223.  
2 Irving PM, Colombel JF, D’Haens G, et al. Risankizumab versus ustekinumab for Simple Endoscopic Score improvement in patients with moderate-to-severe Crohn’s disease: phase 3b sequence trial post-hoc analysis [abstract]. Gut. 2025;74(Suppl. 1):A93.  
3 Raine T, Danese S, Schreiber S, et al. Steroid-sparing effect of risankizumab vs ustekinumab in patients with moderately to severely active Crohn’s Disease: post hoc results from the phase 3b SEQUENCE trial [abstract]. J Crohns Colitis. 2025;18(Suppl. 1):i189.  
4 Loftus EV, Sands BE, Jairath V, et al. Improvement in health-related quality of life in moderate to severe Crohn’s disease patients treated with risankizumab versus ustekinumab: SEQUENCE study [abstract]. Gut. 2025;74:A110. Abstract P31.