SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A post hoc analysis of data obtained from 2 separate clinical trial programs compared endoscopic results of patients with moderate to severe Crohn’s Disease (CD) treated with STELARA versus infliximab.¹
• A post hoc analysis of the UNITI and IM-UNITI clinical trial program of STELARA for the treatment of adults with moderately to severely active CD reported the clinical and endoscopic outcomes of nonpassable or passable strictures.²
• Additional published literature reported outcomes of STELARA treatment in patients with CD and strictures or stenoses through a prospective study, retrospective studies, and case reports.^3-14

CLINICAL DATA

Post Hoc Analyses of the UNITI Clinical Trial Program

Wong et al (2023)¹ conducted a post hoc analysis of 2 clinical trial programs to compare endoscopic outcomes in biologic-naïve patients with moderate to severe CD receiving STELARA versus infliximab.

Study Design/Methods

• The datasets for this analysis of patients treated with STELARA were obtained through the YODA (Yale Open Data Access)#2021-4822 Project.
• Data from patients treated with infliximab were obtained from a study comparing biosimilar and originator infliximab (CT-P13 study).
• Presence of persistent, nonpassable strictures at 1 year among those with nonpassable strictures at baseline was assessed.
• For the evaluation of endoscopic outcomes, propensity score matching was used in a 1:2 ratio of STELARA:infliximab due to fewer participants with endoscopic data in the UNITI program versus the CT-P13 study.

Results

• A total of 220 patients were included, 110 of which received STELARA.
• At baseline, patients had a similar prevalence of nonpassable strictures and disease duration, when matched for propensity. For study population and propensity-matched baseline characteristics, see Table: Baseline Characteristics Among STELARA and Infliximab Groups

• Of the patients with a baseline colonoscopy, a similar proportion of patients treated with STELARA versus infliximab, respectively, had nonpassable strictures that persisted at 1 year:
  • 1/7 (14.3%) vs 5/26 (19.2%); P=0.763
  • Propensity-score matched population: 4/5 (80%) vs 19/36 (52.8%); P=0.250

Narula et al (2021)² conducted a post hoc analysis of 3 large CD clinical trial programs to compare the clinical and endoscopic outcomes of patients with CD receiving STELARA, infliximab, or azathioprine with nonpassable strictures vs those with passable or no strictures. Relevant data regarding STELARA from the UNITI and IM-UNITI clinical trial program is summarized below.

Study Design/Methods

• The datasets for this analysis were obtained through the YODA #2020-4362 Project.
• In the UNITI & IM-UNITI program, endoscopy was not required for study participation; however, an endoscopy substudy was performed on a subset of patients with ileocolonoscopies at baseline, week 8 (end of induction), and week 52 (week 44 of the maintenance study). Patients not eligible for IM-UNITI could still participate in the endoscopy substudy with a week 52 ileocolonoscopy.
• All endoscopies were centrally read.
• There were 334 patients who participated in the substudy. Patients who crossed over between STELARA and placebo were excluded, but those who continuously received STELARA (n=163), or placebo (n=50) were included.
• Simple-Endoscopic Score for Crohn’s Disease (SES-CD) was used for endoscopic scoring:
  • Nonpassable stenosis: SES-CD narrowing subscore of 3
  • Passable stenosis:
    • Single passable narrowing: SES-CD narrowing subscore of 1 for single passable narrowing of 1 segment
    • Multiple passable narrowing: SES-CD narrowing subscore of 2 for multiple passable narrowing of ≥1 segment
  • No stenosis: SES-CD narrowing subscore of 0
• Participants with a nonpassable stenosis and multiple passable stenoses were part of the nonpassable stenosis group.
• The primary objective was the likelihood of converting from nonpassable stenosis to passable stenosis or no stenosis after 1 year of observation.
• Additional outcomes included clinical remission/response and endoscopic remission/response among those with nonpassable and passable stenoses at baseline.

Results

• Of the 163 patients included in this subanalysis:
  • 35 had nonpassable stenosis
  • 15 had passable stenosis
  • 113 had no stenosis
• Of the 35 patients with nonpassable stenosis at baseline, 25 (71.4%) and 10 (28.6%) patients had stenosis located in the ileum and colon, respectively. For clinical and endoscopic outcomes among patients with nonpassable stenosis at baseline, see Table: Baseline Characteristics and Outcomes Among Patients Receiving STELARA with Nonpassable Stenosis at Baseline

• Of the 15 patients with passable stenosis at baseline, 7 (46.7%) and 8 (53.3%) patients had stenosis located in the ileum and colon, respectively. For clinical and endoscopic outcomes among patients with passable stenosis at baseline, see Table: Baseline Characteristics and Outcomes Among Patients Receiving STELARA with Passable Stenosis at Baseline

• In patients without stenosis as baseline, the development of stenosis overtime was also examined, see Table: Development of Stenosis in Patients Without Stenosis at Baseline.

Prospective Study

Liu et al (2024)³ conducted a multicenter, prospective, observational study to evaluate the effectiveness of STELARA therapy in adult patients with symptomatic stricturing CD.

• A total of 28 patients were included in the analysis at baseline (median age, 34 [range 24-46] years; median disease duration, 10 [range 2-216] months; steroid dependent, 35.7%).
• The ileum was the most common site of strictures (67.9%); colonic strictures were observed in 21.4% of patients, and 17.9% of patients had multiple strictures.
• Prior to enrollment, some patients underwent bowel surgery (10.7%), perianal surgery (25.0%), or endoscopic dilation treatment (3.6%) or received other biologics (14.3%).
• The primary endpoint was successful treatment as defined by continuation of STELARA treatment at week 52 without the use of prohibited treatment (corticosteroids, other biologics), endoscopic dilation, or bowel resection. Effectiveness was determined by the relief of stenosis.
  • Success was achieved in 71.4% of patients while 8 were discontinued due to stricture surgery, switching to anti-TNF therapy or resumption of exclusion enteral nutrition.
• For stenosis remission, the SES-CD and DBE-CD score of strictures, respectively, decreased from 6.71±0.18 and 3.85±0.15 to 3.14±0.14 and 3.04±0.24.
• The Crohn’s Disease Obstructive Score (CDOS) significantly decreased from 4.85±0.61 to 1.14±0.39 (P=0.025).
• Assessment of disease activity revealed that STELARA reduced the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) of ultrasound from 71.71±5.23 to 54.73±5.41 (P=0.036).
• Bowel wall thickness <5 mm (P=0.031) was a predictive factor of remission in patients who received STELARA.
• No significant risk of surgery or failure was observed (P=0.25).

Retrospective Studies

El Ouali et al (2023)⁴ conducted a multicenter, observational cohort study to evaluate the outcomes in patients with CD who received STELARA within 6 months of imaging-confirmed symptomatic stricturing small bowel disease.

• Strictures were defined using the CONSTRICT criteria (2 of the following: bowel wall thickening, luminal narrowing, or prestenotic dilation).
• Patients with strictures associated with penetrating disease, ileostomies, or ileal pouch anal-anastomosis were excluded.
• Outcomes assessed included rates of obstructive symptoms, endoscopic balloon dilation (EBD), surgery, and STELARA drug persistence.
• A total of 59 patients were included, 94.9% of whom had received prior biologic agents and 47% of whom had an anastomotic stricture. Median follow-up was 16 months.
• Estimated obstructive symptom rates were 67% and 76% at 12 and 24 months, respectively. Among patients during follow-up, 70% had persistent symptoms and 30% had initial resolution of symptoms followed by recurrence.
• The following outcomes were reported at 12, 24, and 48 months, respectively:
  • EBD rates: 8.1%, 11%, 22%
  • Surgery rates: 29%, 40%, 58%
  • STELARA persistence: 79%, 76%, 52%
• Dose escalation occurred in 29% of patients, with a median time to escalation of 8 months.
• Predictors of STELARA discontinuation were an increased bowel wall thickness (hazard ratio [HR]=1.22, [1.01-1.47]), prior biologic use (HR=1.84, [1.15-2.96]), and obstructive symptom duration (HR=1.01 [1.0-1.03]).
• EBD within 6 months prior to STELARA initiation was associated with an increased risk of surgery (HR=5.45, [1.51-19.6]).
• Penetrating complications, such as fistula or abscess, occurred in 5.1% of patients during follow-up.

St-Pierre et al (2023)⁵ conducted a retrospective, cohort study to assess the changes of terminal ileal CD strictures in patients treated with STELARA.

• Strictures were defined as: increased bowel wall thickness >3 mm, narrowed luminal apposition, and presence of prestenotic dilation or the inability to pass the colonoscope through the narrowed area.
• Outcomes assessed were changes in sonographic parameters (bowel wall thickness, luminal size, prestenotic dilation, length, hyperemia, inflammatory fat, and dysfunctional peristalsis) recorded at baseline versus 12 months after STELARA initiation.
• Of the 18 patients included, the median CD duration was 10 years (Q1-Q3: 8-20 years) and the majority of terminal ileal strictures were surgically naïve (n=12).
• There was significant improvement in bowel wall thickness (8.2 mm vs 7.2 mm, P=0.048) between baseline and at 12 months of STELARA treatment.
• There was no significant difference in the presence of peri-enteric inflammatory fat, stricture-associated hyperemia, or dysfunctional peristalsis. There was also no significant difference between mean stricture length or mean stricture lumen diameter, as seen in Table: Intestinal Ultrasound Parameters at Baseline and 12 Months After STELARA Treatment

Buisson et al (2023)⁶ conducted a multicenter, retrospective study to assess the effectiveness of STELARA vs a second anti-tumor necrosis factor (anti-TNF) agent after failure of a first anti-TNF agent in patients with symptomatic stenosing CD: results of the USTEKNOSIS study.

• Symptomatic strictures were confirmed on endoscopy or imaging after prior exposure to ≥1 anti-TNF agent for the current stricture.
• The primary endpoint was clinical remission (composite endpoint) at 6 months: no pain, no vomiting, no food restriction, no subocclusive episode, no steroids, no surgery, or discontinuation of treatment.
• Of the 70 patients included in this analysis, 34 were receiving STELARA and 36 were receiving anti-TNF agents (29 on infliximab and 7 on adalimumab).
• Concomitant immunomodulators were taken in 8.8% and 63.9% of patients receiving STELARA and anti-TNF agents, respectively.
• Primary failure to anti-TNF agents was reported in 16.7% vs 20.6% and prior exposure to ≥2 biologics were reported in 41.2% vs 8.3% of patients in the STELARA and anti-TNF group, respectively.
• The number and length of stricture were similar in the STELARA group and anti-TNF group.
• After adjustment based on propensity scores, the rate of clinical remission at 6 months was 73.9% and 42.7% in those receiving STELARA vs anti-TNF agents, respectively, P=not significant (NS).
• Predictive factors of remission in patients receiving STELARA were prior bowel resection (P=0.001) and length of stricture <12 cm (P=0.042).
• Risk of treatment discontinuation for failure (HR=2.86, [1.33-6.15], P=0.008) or bowel damage progression (HR=3.90, [1.64-9.24], P=0.003) were higher in patients receiving another anti-TNF agent vs STELARA.
• There was no significant difference regarding the risk of surgery (HR=2.60 [0.70-9.61], P=NS).

Wada et al (2022)⁷ evaluated the efficacy of STELARA on small bowel and stenotic lesions through a retrospective, single-center study.

• Patients who received STELARA for ≥24 weeks and underwent total colonoscopy or double-balloon endoscopy (DBE) before and after treatment were eligible for this study.
• A weight-based dosing regimen of ~6 mg/kg (260 mg for weight ≤55 kg, 390 mg for weight >55-85 kg, and 520 mg for weight >85 kg) was administered every 8 weeks.
• Patients were stratified by responders (Clinical Disease Activity Index [CDAI] <150 or a decrease of >100 points at 24 weeks vs baseline) vs nonresponders.
• Improvement in stenotic lesions were assessed by the SES-CD and modified SES-CD score (a subscore of the SES-CD which measures the appearance of narrowing).
• There were 35 and 15 patients who responded and did not respond to STELARA, respectively. A history of anti-TNF use was reported in 71.4% of responders vs 80% of nonresponders to STELARA, respectively.
• At baseline, the mean SES-CD score prior to STELARA induction was 6.1±5.1 and 13.2±5.3 in responders and nonresponders, respectively. The mean stenotic score was 1.3±1.2 and 1.9±1.2 for the responders and nonresponders, respectively.
• A significant decrease in the SES-CD subscore and modified SES-CD subscore was observed for responders vs nonresponders, respectively:
  • SES-CD subscore (presence of stenotic lesions): 0.6±0.8 vs -0.6±0.7, P<0.001
  • Modified SES-CD subscore (presence of narrowing): 2.4±1.8 vs -0.1±1.2, P<0.001

Bacaksiz et al (2021)⁸ conducted a retrospective study to assess the efficacy of STELARA in patients with CD, including patients with stricturing CD.

• Over 52 weeks, 10 patients with moderate-severe CD were included in this analysis. Of these patients, 7 had stricturing disease. All 7 patients had previously received immunosuppressive agents and ≥1 biologic agent for the treatment of CD.
• Remission was assessed using the CDAI (score <150 points) and Harvey Bradshaw Index (HBI) (score ≤4 points).
• Of the 7 patients with stricturing disease:
  • Patient 1 had a history of colonic stricture and was considered unresponsive. STELARA treatment was discontinued due to the discovery of stricture progression and mucosal worsening on endoscopy at week 26.
  • Patient 4, who also had a diagnosis of ankylosing spondylitis, experienced response and remission, but was discontinued from STELARA therapy and switched to an anti-TNF therapy per recommendation from the rheumatology department.
  • Patient 10 had a history of anal stenosis, continued STELARA treatment and achieved remission until week 44. The patient was operated on for ileus and treatment was discontinued.
  • At the end of week 52, patients 2, 3, 7, and 9 achieved remission according to CDAI/HBI, respectively, vs baseline:
    • Patient 2: 10/0 vs 262/13
    • Patient 3: 7/0 vs 165/7
    • Patient 7: 94/0 vs 195/7
    • Patient 9: 41/2 vs 237/11
• No drug related adverse events were observed in any patient during induction or maintenance therapy with STELARA.

El Ouali et al (2021)⁹ assessed treatment with STELARA or vedolizumab for patients with CD and small bowel associated strictures through a single-center observational cohort study. Summarized are data relevant for STELARA.

• Adult patients who received STELARA within 6 months of objective evidence of stricturing small bowel disease confirmed by abdominal computed tomography or magnetic resonance imaging and as defined by the CONSTRICT criteria (2 of the following: bowel wall thickening, luminal narrowing, prestenotic dilation).
• Patients with strictures associated with penetrating disease, ileostomies, or ileal pouch anal-anastomosis were excluded from this analysis.
• Outcomes assessed included time to recurrence of obstructive symptoms, time to EBD, or time to surgical intervention.
• Of the 21 patients included, 15 received STELARA for a median duration of 6 months. Median duration of follow-up was 14 months. All patients previously received anti-TNF agents.
• At follow-up, 40% of patients developed obstructive symptoms with a median time to recurrence of 7 months.
• EBD was performed in 27% of patients with a median time to dilation of 4 months.
• Surgery was performed in 27% of patients with a median time to surgery of 8 months.
• Persistence of STELARA therapy at 6 months was seen in 100% of patients.

Lambin et al (2020)¹⁰ conducted a multicenter, retrospective cohort study from the Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) to evaluate the outcome and management of patients with CD complicated by a stricture of the upper gastrointestinal tract. Outcomes in patients receiving STELARA treatment are summarized below.

• Patients with a nonpassable symptomatic stricture caused by CD were included in this analysis.
• Clinical efficacy was defined by an improvement of obstructive symptoms according to the physician global assessment (PGA).
• Of the 60 patients included in this analysis, 3% (2 patients) were receiving STELARA.
• In 2 cases which STELARA therapy was used alone, clinical efficacy was achieved in 50% during 4 months.
• In 3 cases which STELARA was used in combination with an immunosuppressant, clinical efficacy was achieved in 67% during 10.5 (interquartile range, 10.3-10.8) months.

Kopylov et al (2014)¹¹ conducted a retrospective, observational, open-label study to evaluate the use of STELARA in patients with CD who were refractory to anti-TNF agents.

• Clinical response was defined as improvement in the patient’s symptoms plus the decision to continue STELARA and was assessed at initial response (up to 12 weeks or the first visit after initiating treatment if the first visit after initiating treatment occurred after 12 weeks), 6 and 12 months, and the last follow-up.
• There were 38 patients included in this analysis. Patients were followed for a mean duration of 7.9±5.2 (range 3-21) months.
• The most common induction regimen was 90 mg at 0, 1, 2 weeks for 82.4% (28/34) of patients; the most common maintenance regimen was 90 mg every 8 weeks for 73.7% (28/38) of patients.
• Of the 38 patients, 42.1% (16 patients) had stricturing CD:
  • Clinical response at the end of follow-up was achieved in 11.1% of patients.

Case Reports

Gupta et al (2024)¹⁴ reported a case of a 40-year-old male with a 13-year history of stricturing colonic and perianal CD.

• Prior treatment history for CD included thiopurines ± anti-TNF therapy.
• Colonoscopy confirmed severe active inflammation with deep ulceration affecting the rectosigmoid colon with a stricture at 35 cm, preventing further passage for colonoscopy.
• The patient was switched from infliximab to STELARA 390 mg IV induction dose followed by STELARA 90 mg subcutaneous (SC) q4w maintenance dose.
  • The decision to administer STELARA SC q4w was based on the severity of inflammation endoscopically and the previously failed anti-TNF therapy.
• After 12 months, clinical (HBI, 0) and biochemical (CRP <2 mg/L) improvement was observed; however, FCP data were unavailable.
• After 24 months, colonoscopy showed ulcer-free mucosal healing with the resolution of the stricture seen at earlier endoscopy.
• The endoscope was able to pass through to the terminal ileum, and histology examination of the distal colon and stricture revealed no signs of acute inflammation.
• No complications associated with STELARA treatment were reported.

Murate et al (2021)¹² reported 2 patients with ileocolonic CD and small intestinal lesions with stenoses.

Patient 1

• A 40-year-old female with past treatment history (PTH) of 5-aminosalicylic acid (5-ASA) for 3 years.
• Transoral DBE showed a shallow longitudinal ulcer and 2 stenoses with a deep ulcer (with passage of the endoscope) in the middle ileum. Gastrografin enterography on DBE confirmed another stenotic lesion (with no passage of the endoscope due to deep ulceration) in the lower ileum.
• Transanal DBE revealed a longitudinal ulcer in the terminal ileum and stenosis (detected by gastrografin enterography; no passage of the endoscope) in the lower ileum.
• CD was diagnosed and STELARA was initiated; at 24 and 72 weeks, transoral and transanal DBEs were performed:
  • At 24 weeks:
    • The patient had no symptoms and normal blood stool frequency (2×/day).
    • Transoral DBE revealed scarring of the shallow longitudinal ulcer.
    • Transanal DBE revealed deep longitudinal ulcers were still present, but shrinking and becoming more shallow.
    • Stenosis at the longitudinal ulcer site in the middle ileum was improved and the endoscope could now pass. The colonic lesion was also improved.
  • At 72 weeks:
    • The patient was symptom-free with normal stool consistency (stool frequency: 1-2×/day).
    • Transoral DBE revealed shallow longitudinal ulcers in the scarring stage but inconspicuous.
    • Transanal DBE revealed deep ulcer area was flattened, reduced, and disappeared. The stenotic site was dilated and inconspicuous.
    • Mucosal healing was noted.

Patient 2

• A 50-year-old female with a PTH of combination therapy with 5-ASA, an immunomodulator, and a steroid for 25 years, followed by addition of infliximab therapy due to disease activity. Stenosis was observed during endoscopy with ulcers in the middle ileum.
• Transoral DBE revealed multiple longitudinal ulcers through the ileum; 3 stenoses in the ileum were revealed and confirmed through gastrografin enterography (including a stenosis with no passage of the endoscope).
• Infliximab was administered to the patient but ineffective and the treatment was then switched to STELARA.
• At 24 and 72 weeks after introduction of STELARA, transoral and transanal DBEs were performed:
  • At 24 weeks:
    • The patient had no symptoms and normal stool frequency (2×/day); abdominal pain was reported 1× every 2 days.
    • Through transoral DBE, longitudinal ulcers were shallow with reduced edema. Some ulcers had become scarred.
    • Transanal DBE revealed circumferential ulcers were shorter with reduced edema. The stenosis was improving but the endoscope still could not pass.
  • At 72 weeks:
    • Transoral DBE showed longitudinal ulcers at observable range that were all scarred.
    • Transanal DBE still revealed circumferential ulcers but were shorter, mostly covered by regenerating mucosa, and the endoscope could now pass.
    • The mucosa was noted to be near remission.

Murate et al (2019)¹³ reported the treatment with STELARA in a 20-year-old female with ileocolonic CD and small intestinal stenoses.

• Patient presented with severe abdominal pain and underwent DBE with retrograde route which revealed several ulcerated lesions with edema and 4 stenotic sites in the middle-lower ileum. Two of these stenoses were not passable by the endoscope and were dilated by balloon to 10-11 mm. After dilation, DBE could pass through all 4 stenotic sites.
• STELARA was initiated as a remission induction therapy. After 24 weeks, retrograde DBE was performed. All 4 stenotic sites were passable and the lumen at the 2 stenotic sites further dilated beyond what was observed after EBD.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 24 January 2025.