SUMMARY

• Please refer to the local labeling for relevant information on the use of STELARA in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC).
• Summarized below is data from meta-analyses on the effectiveness and safety of STELARA and vedolizumab (VDZ) in patients with CD.^1-3
• Additionally, relevant data from prospective and retrospective studies that compared the effectiveness and safety of STELARA and VDZ in patients with CD is also described below.^4-11

CLINICAL DATA

Meta-analyses

Parrot et al (2022)¹ conducted a systematic review with meta-analysis to compare the effectiveness of STELARA and VDZ in patients with CD refractory to anti-tumor necrosis factor (TNF) therapies.

Methods

• Studies that compared the efficacy of STELARA and VDZ after failure or intolerance to anti-TNF in patients with CD were considered eligible.
• The search was conducted on March 27, 2021, across PubMed^®, EMBASE^®, and the Cochrane Library.
• Outcomes of interest for the meta-analysis included clinical remission at weeks 14 and 52 (Harvey-Bradshaw Index [HBI] ≤4 or Crohn's Disease Activity Index [CDAI] <150), steroid-free clinical remission (SFR) at weeks 14 and 52, biological remission (C-reactive protein [CRP] ≤5 mg/L or fecal calprotectin [FC] ≤250 µg/g) at weeks 14 and 52.
• The primary analysis was based on 5 studies with adjusted results.

Results

• A total of 1026 patients received either STELARA (n=659) or VDZ (n=367) and were included in the analyses.
• Follow-up duration ranged from 24 to 104 weeks.
• At week 14, the rates of clinical remission, SFR, and biological remission were similar between the 2 groups:
  • Clinical remission rate: Odds ratio (OR), 1.36; 95% confidence interval (CI), 0.74-2.47
  • SFR rate: OR, 1.24; 95% CI, 0.79-1.92
  • Biological remission rate: OR, 0.80; 95% CI, 0.50-1.28
• At week 52, the rates of clinical remission, SFR, and biological remission were higher for the STELARA group:
  • Clinical remission rate: OR, 1.87; 95% CI, 1.18-2.98
  • SFR rate: OR, 1.56; 95% CI, 1.23-1.97
  • Biological remission rate: OR, 1.86; 95% CI, 1.03-3.37

Kawalec and Moćko (2018)² conducted an indirect comparison to evaluate the clinical efficacy and safety of STELARA and VDZ, in patients with active CD who were intolerant or unresponsive to previous anti-TNF therapies.

Methods

• Randomized, double-blind studies comparing STELARA or VDZ with placebo in patients with CD were included.
• A systematic review was conducted up to April 30, 2017, across EMBASE^®, MEDLINE^® (via PubMed^®), and Cochrane Central Register of Controlled Trials (CENTRAL).
• Indirect comparison results were expressed as relative risks (RRs) with 95% CI for efficacy outcomes and adverse events (AEs).
• To calculate relative parameters, the fixed effects model was applied when there was no statistical heterogeneity, and the random effects model was applied when heterogeneity was present (P<0.10).

Results

• Systematic review revealed 5 randomized controlled trials (RCTs). Three studies compared STELARA and placebo (CERTIFI, UNITI-1, IM-UNITI) and 2 studies compared VDZ and placebo (GEMINI-2, GEMINI-3).
• Clinical response was defined as ≥100-point decrease in the CDAI and was assessed during the induction phase.
  • At week 6, no statistically significant difference was observed between STELARA and VDZ in achieving clinical response during the induction phase (relative benefit [RB]: 1.14; 95% CI, 0.65-1.99; P=NS).
• Clinical remission was defined as a CDAI score of ≤150 and was assessed during the induction and maintenance phase.
  • At week 6, STELARA 6 mg/kg was as effective as VDZ 300 mg at inducing clinical remission (RB: 1.16; 95% CI, 0.54-2.48; P=NS).
  • After 52 weeks of treatment, no significant difference was observed between STELARA and VDZ in achieving clinical remission in the maintenance phase among patients intolerant or refractory to TNF-antagonist treatment (RB: 0.72; 95% CI, 0.30-1.68; P=NS).
• During the induction and maintenance phases, no significant differences were observed in the safety profile of STELARA and VDZ, with the RR of 0.93 during the maintenance phase (95% CI, 0.81-1.08; P=NS).

Hather et al (2017)³ conducted a network meta-analysis to evaluate the efficacy of STELARA and VDZ in patients with moderately to severely active CD.

Methods

• Induction and maintenance data were obtained from phase 3, randomized, double-blind, placebo-controlled studies: GEMINI II for VDZ and UNITI-1, UNITI-2, and IM-UNITI for STELARA.
• A Bayesian network meta-analysis was performed using OpenBUGS v3.2.2. To account for variability in placebo effects across trials, a binomial likelihood and a logit link function were used in a fixed effects model.
• Clinical remission was defined as a CDAI ≤150.
• Week 6 induction data were extracted for placebo, STELARA 6 mg/kg, and VDZ 300 mg, while week 52 maintenance data were extracted for placebo, STELARA 90 mg every 12 weeks (q12w) and every 8 weeks (q8w), and VDZ 300 mg q8w and every 4 weeks (q4w).

Results

• Results were stratified by prior exposure to anti-TNF therapies.
• At week 6, the OR for clinical remission between STELARA 6 mg/kg and VDZ 300 mg were not statistically significant and are reported below:
  • Anti-TNF nonrefractory patients: 0.99
  • Anti-TNF refractory patients: 1.63
• At week 52, the OR for clinical remission between STELARA 90 mg q8w and VDZ 300 mg q8w were not statistically significant and are reported below:
  • Anti-TNF naive patients: 0.67 (95% CI, 0.23-1.99)
  • Anti-TNF refractory patients: 0.73 (95% CI, 0.23-2.28)

Registry Data

Helm-Wiken et al (2025)⁴ evaluated the effectiveness and dosing of STELARA vs VDZ in patients with UC after failure of at least 1 TNF inhibitor therapy.

Study Design/Methods

• Patients who were started on either VDZ (2016-2019) or STELARA (2020-2022) were followed for 1 year after initiation of therapy or until discontinuation. Data were obtained from electronic patient journal and a local inflammatory bowel disease (IBD) registry in Norway.

Results

• A total of 116 patients were included in the study: STELARA, n=57; VDZ, n=59.
• The clinical remission rate increased significantly in both groups, with no difference between STELARA and VDZ at weeks 0 (OR, 2.1 [0.9-4.5]) and 52 (0.9 [0.3-2.3]). For further details, see Table: Clinical Outcomes at Weeks 0 and 52 for STELARA vs VDZ.

García et al (2024)⁵ evaluated the short term and long-term effectiveness and safety of STELARA and VDZ in patients with CD and also identified the predictive factors of clinical response and remission.

Study Design/Methods

• This multicenter study included adult patients between January 1, 2012, to December 30, 2020 from the ENEIDA registry, a prospectively maintained nationwide database supported by the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU).
• Patients included in the study were treated for CD with STELARA or VDZ after anti-TNF (primary or secondary) failure or intolerance.
• STELARA induction therapy consisted of a 6 mg/kg weight-based intravenous (IV) dose followed by 90 mg subcutaneous (SC) q8w or q12w.
• VDZ was administered as an initial induction IV infusion of 300 mg at weeks 0, 2, and 6 followed by 300 mg q8w. An additional dose of 300 mg at week 10 was permitted.
• Effectiveness was assessed at weeks 8 and 16 during the induction period and every 6 months during the maintenance phase.
• CD was classified as per the Montreal classification and clinical activity and treatment response was assessed using HBI.
  • Active disease was defined as an HBI score of ≥5 points and clinical remission was defined as an HBI score of <5.
  • Corticosteroid-free clinical remission was defined as an HBI score of <5 with no corticosteroid administration at a certain visit.
  • Clinical response was defined as a reduction in HBI by ≥3 points from baseline alongside clinical remission criteria.
• Loss of response:
  • HBI >4 leading to dose escalation, addition of another medication, change to another drug, or surgery

Results

• A total of 835 patients were included in the study: STELARA, n=628; VDZ, n=207.
• The median follow-up time from start of therapy to database lock was 2.8 years (interquartile range; IQR, 2.0-3.6) and 4.7 years (IQR, 3.2-5.5) for patients treated with STELARA and VDZ, respectively.

Short-term Effectiveness

• Effectiveness was evaluated in 597 patients (STELARA, n=445; VDZ, n=152) with active disease at the start of treatment (HBI >4 points).
• A total of 13 patients discontinued treatment during the induction phase: 12 in the STELARA group and 1 in the VDZ group.
• In a multivariate analysis through week 16, STELARA was associated with higher likelihood of clinical outcomes below when compared to VDZ:
  • Clinical response: OR, 1.84; 95% CI, 1.27-3.18
  • Clinical remission: OR, 2.01; 95% CI, 1.27-3.18
  • Corticosteroid-free clinical remission: OR, 1.84; 95% CI, 1.12-3.03

Long-term Effectiveness

• Effectiveness was evaluated in 584 patients followed up for at least 6 months.
• In the multivariate analysis through 1 year, the likelihood of achieving the clinical outcomes below was significantly higher in patients receiving STELARA vs VDZ:
  • Clinical response: OR, 1.80; 95% CI, 1.17-2.79
  • Clinical remission: OR, 1.73; 95% CI, 1.10-2.70
  • Corticosteroid-free clinical remission: OR, 1.69; 95% CI, 1.07-2.68

Loss of Response and Therapy Discontinuation

• Overall, 770 patients reached remission at week 16, and 514 lost responses over time (STELARA, n=360; VDZ, n=154; P<0.001).
• A total of 350 patients discontinued treatment at the last study visit:
  • STELARA: n=202 (95% CI, 28.5-35.8)
  • VDZ: n=148 (95% CI, 65.3-77.6)
• The discontinuation ratio was 19 per 100 person-years (PY) and 49 per 100 PY for STELARA and VDZ, respectively (P<0.001).
• The primary reason for treatment discontinuation was primary nonresponse, followed by secondary nonresponse.

Safety

• Overall, 11.6% (n=97) of patients experienced at least 1 AE: STELARA, n=67; VDZ, n=30 (P= non-significant [NS]); incident rate of AEs (5.3 and 6.6 per 100 PY for STELARA and VDZ, respectively).
• Infection was the most common AE, followed by arthralgia and skin disorders.
• Serious adverse events (SAEs) occurred in 22 patients: STELARA, n=13; VDZ, n=9 (P=NS).
• AEs leading to treatment discontinuation were reported in 17 patients in the STELARA group vs 13 in the VDZ group (P>0.05).
• One patient died in the VDZ group due to infectious arthritis complicated by septic shock.

Prospective Study

Bokemeyer et al (2024)⁶ presented 1-year maintenance therapy results from the prospective, observational real world RUN-UC study that evaluated the effectiveness of STELARA compared with anti-TNF therapy and VDZ in patients with UC. Data reported below are results for STELARA and VDZ.

Methods

• A total of 476 patients with UC were included in the analysis.
  • STELARA: n=147 (bio-naïve, n=12)
  • VDZ: n=161 (bio-naïve, n=105)
• Propensity score (PS) adjustment eliminated systemic differences in baseline parameters among the groups, including sex distribution (STELARA/VDZ, 42.2%/50.3% males) and presence of extraintestinal manifestations (STELARA/VDZ, 25.2%/19.9%). The bio-experienced characteristic was also equalized among the groups.

Results

• The PS-weighted effectiveness (mITT analysis) of STELARA in terms of response and clinical and steroid-free remission at month 12 was similar to that of VDZ. This similarity was also observed without PS weighting, with a clinical remission rate of 33.1% for STELARA and 38.1% for VDZ.
• Patients in all treatment groups showed significant improvements in the quality of life (QoL), measured using the EuroQoL-visual analog scale (EQ-VAS), after 12 months of treatment.

Retrospective Studies

Ferrante et al (2023)⁷ reported the clinical effectiveness and safety of STELARA and VDZ from a multicenter, observational, retrospective cohort study (EVOLVE expansion study) in patients with CD.

Study Design/Methods

• Biologic-naïve adult patients with CD who initiated STELARA or VDZ treatment between 2016 to 2021 were included in the study.
• Cumulative rates of clinical response, remission, mucosal healing, and treatment persistence were evaluated over 12, 24, and 36 months.

Results

• A total of 623 patients with CD who received either STELARA (n=276) or VDZ (n=347) were included.
• Cumulative rates of clinical outcomes over 36 months were similar between STELARA- and VDZ-treated patients. For clinical outcomes, see Table: Cumulative Clinical Outcomes During 12, 24, and 36 Months.

• In the STELARA group, 53 SAEs (including 5 serious infections [SIs]) were reported in 27/276 (9.8%) and 2/276 (0.7%) patients, respectively.
• ln the VDZ group, 54 SAEs (including SIs) and 12 SIs were reported in 35/347 (10.1%) and 9/347 (2.6%) patients, respectively.
• No significant differences were observed in the risk of CD exacerbations (hazard ratio [HR], 1.01; 95% CI, 0.68-1.49; P=NS) and CD-related surgeries (HR, 1.80; 95% CI, 0.69-4.73; P=NS) between STELARA- and VDZ-treated patients.

Yang et al (2023)⁸ evaluated the effectiveness of STELARA and VDZ in patients with CD, including both TNF-inhibitors (TNFi)-naïve and TNFi-exposed patients with CD.

Study Design/Methods

• This multicenter, observational, real-world study included adult patients with CD between May 2020 and July 2023 who received ≥1 dose of STELARA or VDZ for luminal disease.
• STELARA was administered as an IV induction (~6 mg/kg) followed by a maintenance dose of 90 mg SC q8w or q12w.
• VDZ 300 mg IV was administered at weeks 0, 2, and 6 for induction, followed by a maintenance dose q8w.

Outcomes and Definitions

• Clinical outcomes were evaluated at weeks 0, 26, and 52.
• Primary outcome: steroid-free remission at weeks 26 and 52
• Secondary outcomes: clinical remission at weeks 26 and 52 and AEs during follow-up
• Clinical remission was defined as CDAI ≤150.
• Steroid-free remission was defined as CDAI ≤150 with steroid use below the equivalent of prednisolone 10 mg/day.
• CRP normalization: <5 mg/L

Results

• A total of 654 patients were included (STELARA, n=475; VDZ, n=179), of whom 536 met the inclusion criteria (STELARA, n=386; VDZ, n=150).

Clinical and Steroid-Free Remission

• At week 26, in the overall adjusted population, STELARA was more effective than VDZ in the TNFi-exposed patients:
  • Steroid-free remission (55.4% vs 46.1%; P=0.003; OR, 1.451; 95% CI, 1.140-1.850)
  • Clinical remission (56.4% vs 47.8% (P=0.005; OR, 1.413; 95% CI, 1.109-1.800)
• Among TNFi-naïve patients, no significant difference was observed between STELARA and VDZ:
  • Steroid-free remission (65.5% vs 59.6%; P=NS; OR, 1.289; 95% CI, 0.900-1.848)
  • Clinical remission (66.5% vs 59.6%; P=NS; OR, 1.348; 95% CI, 0.940-1.935).
• Among TNFi-exposed patients, STELARA was superior to VDZ:
  • Steroid-free remission (46.0% vs 33.4%; P=0.003; OR, 1.698; 95% CI, 1.203-2.404)
  • Clinical remission (47.0% vs 36.7%; P=0.015; OR, 1.531; 95% CI, 1.089-2.158)
• At week 52, in the overall adjusted population, STELARA was significantly more effective than VDZ:
  • Steroid-free remission in the overall adjusted population (65.8% vs 37.5%; P<0.001; OR, 3.207; 95% CI, 2.364-4.369)
• Subgroup analyses showed superiority of STELARA to VDZ for steroid-free remission in both TNFi-naïve patients (79.4% vs 49.0%; P<0.001; OR, 4.029; 95% CI, 2.437-6.780) and TNFi-exposed patients (55.6% vs 29.7%; P<0.001; OR, 2.965; 95% CI, 1.985-4.464).

Safety

• The rate of AEs was not statistically significant between the STELARA and VDZ groups (4.9% and 6.7%, respectively; P=NS).
  • STELARA-treated patients: Clostridium difficile associated symptomatic enteritis (n=1), secondary tuberculosis infection and suspended treatment (n=1), rashes that resolved after anti-allergic treatment (n=8), joint pain (n=5), upper respiratory tract infection (n=4)
  • VDZ-treated patients: C. difficile associated symptomatic enteritis (n=3), rashes (n=4), joint pain (n=1), fatigue (n=2).

Meyer et al (2022)⁹ evaluated the efficacy of STELARA and VDZ in patients with UC who failed anti-TNF therapy, using data from 2 multicenter cohort studies conducted at French Groupe d’Etudes Therapeutiques des Affection Inflammatoires du tube Digestif (GETAID) centers.

Study Design/Methods

• Patients with active UC who had an inadequate response to, lost response to, or were intolerant to conventional therapy and at least 1 anti-TNF agent between June 2014 and December 2014 (OSERV-IBD) and January 2019 and September 2019 (UC-USTEK) were included in the study.
• STELARA was administered as 6 mg/kg IV infusions at week 0 for induction therapy; this was followed by maintenance therapy every 4 to 8 weeks per the investigator’s discretion. Patients receiving modified 270 mg SC induction therapy were also included.
• VDZ was administered as 300 mg IV infusions at weeks 0, 2, and 6 for induction therapy; this was followed by maintenance therapy every 4 to 8 weeks per the investigator’s discretion.
• The primary endpoint was steroid-free clinical remission, defined by a partial Mayo Clinic score of ≤2, with a combined stool frequency and rectal bleeding subscore of <1.
  • For induction therapy, steroid-free clinical remission was evaluated at week 14 in the VDZ group and between weeks 12 and 16 in the STELARA group. For maintenance therapy, steroid-free clinical remission was evaluated at week 52 in both groups.

Results

• A total of 121 patients with UC (OBSERV-IBD) who received VDZ and 97 patients with UC (UC-USTEK) who received STELARA were included.

Efficacy

• For comparative effectiveness between STELARA and VDZ at weeks 14 and 52, see Table: Comparative Effectiveness of STELARA and VDZ.

Lenti et al (2022)¹⁰ conducted a retrospective cohort study that compared the clinical effectiveness and safety of STELARA and VDZ as second-line treatment in patients with CD who failed anti-TNFα therapy.

Study Design/Methods

• This multicenter study (Cross Pennine study II) conducted across 8 IBD centers included adult patients through the electronic medical records who initiated STELARA from January 2017 to January 2020, or VDZ from August 2014 to June 2017.
• STELARA was initially administered as a weight-based IV infusion followed by 90 mg SC injection after 8 weeks and thereafter a maintenance dose of 90 mg SC q8w or q12w.
• VDZ was given as 300 mg IV infusion at weeks 0, 2, and 6, and q8w thereafter, with an additional dose at week 10 for 7 patients.

Outcomes and Definitions

• Primary outcome: 3- and 12-month short- or medium-term clinical effectiveness and safety profile of STELARA
• Clinical remission at 14 and 52 weeks (±2 weeks): physician global assessment (PGA) score of 0 (complete relief or marked improvement)
• Clinical response at 14 and 52 weeks (±2 weeks): PGA score of 1 (partial though significant improvement)
• HBI score: remission defined by HBI ≤4; response defined by reduction of at least 3 points
• Primary failure: inadequate clinical response after induction
• Loss of response: inadequate response after induction
• Treatment failure: patients who stopped STELARA in weeks 14-52 in the 52-week analysis

Results

• In total, 282 and 118 patients were included in the final STELARA and VDZ groups, respectively.
• Of 282 patients, 200 (70.9%) achieved clinical response or remission at 14 weeks, and of 259 patients, 162 (62.5%) achieved clinical response or remission at 52 weeks.
• A total of 101 of 282 (35.8%) patients discontinued STELARA, with primary failure and loss of response being the most common reasons, followed by AEs and need for surgery.

Safety Outcomes

• A total of 74 AEs were reported in 69 (24.5%) patients treated with STELARA, with 26 classified as serious (life-threatening or requiring hospital admission).
• Among these SAEs, 6 neoplastic disorders and 1 obstetric complication (premature rupture of membranes) were reported.
• Most patients reporting an AE were on STELARA monotherapy (STELARA vs VDZ, 81.1% vs 28.6%); while few patients were on immunosuppressant or systemic steroid (STELARA vs VDZ,18.9% vs 71.4%).
• The cumulative incidence of severe AEs and infectious diseases in the STELARA and VDZ groups was 8.3 and 17.2 per 100 PY, respectively.

Onali et al (2022)¹¹ conducted a retrospective cohort study that compared the effectiveness of STELARA and VDZ as second-line treatments in patients with CD across 20 Italian IBD referral centers.

Study Design/Methods

• This observational, real-world, multicenter cohort study included patients with a confirmed diagnosis of CD for at least 3 months with primary or secondary failure or intolerance to TNFi between January 2016 to December 2020.
• STELARA 6 mg/kg IV was administered at induction, followed by a maintenance dose of 90 mg SC q8w or q12w.
• VDZ was administered as 300 mg IV at weeks 0, 2, and 6 for induction, followed by maintenance doses q4w or q8w.

Outcomes

• Primary outcome was clinical response at week 26, defined as a reduction in HBI by ≥3 from baseline or achievement of HBI <5 in those with baseline HBI ≤7.
• Secondary outcomes:
  • Clinical response at week 52
  • Clinical remission and SFR at weeks 26 and 52, defined as HBI ≤4 with or without steroids

Results

• A total of 470 patients were included in the study: STELARA, n=239 (50.9%); VDZ, n=231 (49.1%).

Effectiveness: Overall Population Analysis

• At week 26, in the weighted overall population treated with STELARA and VDZ, respectively:
  • Clinical response: 60.1% and 65.4% (P=NS)
  • Clinical remission: 42.1% and 44.8% (P=NS)
  • SFR: 38.3% and 40.7% (P=NS)
• At week 52, STELARA and VDZ, respectively:
  • Clinical response: 64.6% and 68.4% (P=NS)
  • Clinical remission: 42.5% and 55.5% (P=0.010)
  • SFR: 40.6% and 51.1% (P=0.038)
• At week 26, STELARA and VDZ, respectively:
  • CRP normalization: 50.0% and 54.0%
  • Mean±standard deviation (SD) FC: 294±46 and 296±59 mg/kg
• At week 52, in the weighted overall population treated with STELARA and VDZ, respectively:
  • CRP normalization: 56.3% and 61.5%
  • Mean±SD FC: 204±38 and 261±73 mg/kg
• At baseline, in the weighted overall population treated with STELARA and VDZ, respectively:
  • Mean±SD FC: 741±160 and 516±83 mg/kg

Safety Outcomes

• AEs were reported in 35 (14.6%) patients in the STELARA group and 39 (16.3%) patients in the VDZ group, most of which were related to disease activity: STELARA, n=17 (7.1%); VDZ, n=24 (10.4%).
• STELARA group:
  • The most common AEs were arthralgia (n=2) and pneumonia (n=2).
  • One SAE required hospitalization for abdominal abscesses, which resolved after radiologic drainage and antibiotic therapy.
• VDZ group:
  • The most common AEs were nasopharyngitis (n=5), arthralgia (n=2), and pneumonia (n=2).
  • Two patients had more than 1 AE (cellulitis and eczema; cholestasis and hyperamylasemia).
  • One SAE required hospitalization for sepsis related to a central venous catheter infection, which was controlled with IV antibiotic therapy.
• No deaths were reported in either treatment group.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 29 January 2025.