STELARA®
(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: 12/27/2024
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
Abbreviation: 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.
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e
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.
| 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.
| Endpoint | STELARA N=265, % (95% CI)b | RZB N=255, % (95% CI)b | Adjusted Differencec, % Points (95% CI) | P-Valuec |
|---|---|---|---|---|
| Primary endpoints | ||||
| Clinical remission at week 24d | 39.5 (31.3-47.7) | 58.6 (50.1-67.1) | 18.4 (6.6-30.3)e | - |
| Endoscopic remission at week 48f | 16.2 (11.8-20.7) | 31.8 (26.1-37.5) | 15.6 (8.4-22.9) | <0.001 |
| Secondary endpoints | ||||
| Clinical remission at week 48g | 40.8 (34.8-46.7) | 60.8 (54.8-66.8) | 19.7 (11.3-28.1) | <0.001 |
| Endoscopic response at week 24h | 26.4 (21.1-31.7) | 45.2 (39.1-51.3) | 18.9 (10.9-26.9) | <0.001 |
| Endoscopic response at week 48h | 21.9 (16.9-26.9) | 45.1 (39.0-51.2) | 23.3 (15.4-31.2) | <0.001 |
| Glucocorticoid-free endoscopic remission at week 48f,i | 15.5 (11.1-19.8) | 31.4 (25.7-37.1) | 15.9 (8.8-23.1) | <0.001 |
| Glucocorticoid-free clinical remission at week 48g,i | 40.4 (34.5-46.3) | 60.8 (54.8-66.8) | 20.1 (11.7-28.4) | <0.001 |
| 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. gClinical remission at week 48 was assessed among 100% of the ITT population. hEndoscopic 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). i | ||||
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.
| 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. | ||||
| 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. | ||||
LITERATURE SEARCH
References
| 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. |