SUMMARY  

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• The efficacy and safety of STELARA in pediatric patients with ulcerative colitis (UC) were evaluated in a prospective study, retrospective studies, and case reports.^1-8

clinical data

Prospective Study

Dhaliwal et al (2021)¹ evaluated the serum concentrations and efficacy of STELARA in children and adolescents (2-17 years of age) with UC who were refractory to treatment with biologics.

Study Design/Methods

• This was an open-label, prospective study of pediatric patients from 12 academic pediatric inflammatory bowel disease (IBD) centers identified through a Canadian database.
• Children were included in this intention-to-treat analysis if they were treated with intravenous (IV) STELARA following the failure of infliximab.
• All patients received STELARA via IV induction without concomitant immunomodulators:
  • 260 mg for patients weighing 18.3-52.6 kg (n=13)
  • 390 mg for patients weighing 36-76.1 kg (n=11)
  • 520 mg for patients weighing 74.8 kg (n=1)
• Subcutaneous (SC) injections of STELARA 90 mg were scheduled to begin at week 8, except for the smallest child who received 45 mg.
• The standard every 8-week dosing frequency could be shortened after the first SC dose per the discretion of the treating physician based on continuing symptoms.
• Baseline disease activity was categorized using the Pediatric Ulcerative Colitis Activity Index (PUCAI). Endoscopic findings were documented using the Mayo endoscopic score (MES).
• Disease activity and medication usage was recorded as needed and routinely every 6 months.
• Ustekinumab serum levels were also measured by enzyme-linked immunosorbent assay (ELISA) prior to SC injections.
• The primary outcome of this study was steroid-free clinical remission (PUCAI <10 and no corticosteroid usage for ≥4 weeks) on continued STELARA therapy with an intact colon at week 52.
• Secondary and other outcomes included:
  • Steroid-free clinical remission at week 26
  • Sustained steroid-free clinical remission (no corticosteroid usage between weeks 26 and 52)
  • Endoscopic improvement (rectosigmoid Mayo score ≤1 in those with pre-STELARA score ≤2); fecal calprotectin (FCP) <250 µg/g was accepted as endoscopic improvement
  • Biomarker remission (FCP score <250 µg/g)
  • Colectomy rate at 1 year

Results

Baseline Characteristics

• There were 25 children with UC analyzed in this study; the median age was 14.8 years (interquartile range [IQR], 12.3-16.2) and the mean duration of UC was 2.3 years (IQR, 1.1-4.2) at STELARA initiation.
• Previous biologic failure to one class (anti-tumor necrosis factor [TNF] agent) was reported in 13 (56%) patients; 12 (44%) patients had previous biologic failure to 2 classes (anti-TNF agent and vedolizumab).
• Additionally, 17 patients were receiving concomitant corticosteroids at the time of STELARA initiation, and no patients were receiving a concomitant immunomodulator.
• The mean STELARA dose was 6.4 mg/kg (IQR, 5.5-7.5).

Steroid-Free Clinical Remission and Endoscopic Improvement

• Steroid-free clinical remission was achieved in 11/25 (44%) children at week 52. This included 9 (69%) of 13 children with previous biologic failure to anti-TNF agents vs 2 (17%) children with previous biologic failure to anti-TNF agents and vedolizumab (P=0.008).
• For steroid-free clinical remission at months 6 and 12, sustained steroid-free clinical remission, and endoscopic improvement, see Table: Rates of Steroid-Free Clinical Remission and Endoscopic Improvement.

• A multivariate analysis that adjusted for age and sex found the odds ratio of achieving steroid-free clinical remission at week 52 following previous failure to only an anti-TNF agent vs anti-TNF agent and vedolizumab was 17.4 (95% confidence interval [CI],
  1.6-190).
• Among 8 of the 11 patients who achieved steroid-free clinical remission at week 52 and had data >1 year at follow-up, remission had been maintained to ≥72 weeks, including 2 patients with previous failure to anti-TNF agents and vedolizumab and 5 patients with previous failure to anti-TNF agents only.
• There were 5 patients who discontinued treatment after receiving 1 IV dose of STELARA due to colectomy (n=4) and parental choice (n=1). Another 4 patients discontinued STELARA during maintenance due to colectomy (n=2) and initiation of other treatment (n=2).

Ustekinumab Concentrations and Anti-Drug Antibodies

• Of the 20 patients initiating maintenance therapy, 14 (70%) patients had serum ustekinumab levels and anti-drug antibody levels measured at the median time of 30.9 weeks (IQR, 22.1-55.8).
• The median trough ustekinumab concentration was 5.2 µg/mL (IQR, 4.0-9.7); no patient developed detectable antibody levels to STELARA.
• Greater exposure to STELARA (dosing every 4 weeks vs every 8 weeks) was not associated with a superior rate of clinical remission.
• During the maintenance phase of treatment with STELARA, median ustekinumab levels were higher in patients with active colitis (all with dosing interval already empirically shortened to 4 weeks) than patients in clinical remission (9.5 µg/mL [IQR, 4.7-11.8] vs 3.9 µg/mL [IQR, 2.7-6.2], respectively; P=0.02).

Endoscopic Outcomes and Biomarker Remission

• Patients who achieved the primary endpoint (n=11) also underwent a colonoscopic reassessment (n=5) and/or FCP determination (n=9) to verify more than symptom resolution. Endoscopic improvement was evident in 7 of these 9 patients.
  • Of the 9 patients with stools examined at a median time of 51.1 weeks (IQR, 34.6-56.0), FCP was <250 µg/g in 5 patients (baseline median FCP, 863 µg/g [IQR, 759-2100]).
  • Of the 5 patients who underwent a colonoscopic reassessment at a median time of 51.4 weeks (IQR, 29.1-91.5), the MES was 0 or 1 in 4 of these patients (baseline MES ≥2).
• No adverse events were reported with treatment of STELARA.

Retrospective Studies

Alhadab et al (2024)² conducted a single-center retrospective cohort study on the clinical effectiveness and safety of STELARA in children and adolescents with IBD from a single tertiary hospital in Saudi Arabia.

Study Design/Methods

• This study included patients diagnosed with Crohn’s disease (CD) or UC at <16 years of age who had received the first dose of STELARA between January 2017 and February 2022 with a minimum follow-up of 1 year.
• Response to therapy was assessed by using clinical scores, laboratory markers, the need for corticosteroid therapy, and both endoscopic and pathologic measures.
• PUCAI was used to assess UC clinical activity.
• Clinical remission was defined as a PUCAI score of ≤10.
• Patients in clinical remission without corticosteroids were considered in steroid-free remission.
• Biochemical remission was defined as FCP and C-reactive protein (CRP) levels ≤250 μg/g and 5 g/dL, respectively.
• Patients were divided into 2 groups based on clinical remission at week 52:
  • Group I: Patients who achieved clinical remission
  • Group II: Patients who did not achieve clinical remission
• Endoscopic findings were documented using MES, with endoscopic remission defined as an MES of 0.
• Primary nonresponse was defined as failure to achieve a response to induction therapy (clinical, biochemical, or endoscopic) despite reaching therapeutic levels.
• Secondary nonresponse referred to patients who had previously responded to a biologic but experienced deterioration or relapse while still on the same biologic therapy.
• All patients received a single IV induction dose:
  • 9 mg/kg for patients weighing 10 to <40 kg (maximum dose of 260 mg)
  • 390 mg for patients weighing >40 kg
• Maintenance doses were given SC:
  • 2-4 mg/kg for patients weighing 10 to <40 kg (minimum dose of 45 mg and maximum dose of 90 mg)
  • 90 mg for patients weighing >40 kg

Results

Baseline Characteristics

• Of the 13 patients included in this analysis, 5 (38.5%) had UC (group I, 4 [80%]; group II, 1 [20%]), with a median age of 13 years (IQR, 11.5-14).
• STELARA treatment was initiated after a median of 3 years (IQR, 2.3-7) of diagnosis.
• Five (41.7%) patients received corticosteroids at induction.
• All patients had prior exposure to ≥1 anti-TNF drug before the start of STELARA, with a median biologic treatment duration of 2 years (IQR, 1.3-5).

Clinical and Biochemical Response to STELARA

• Overall, 10 (76.9%) and 6 (46.2%) patients achieved clinical remission and biochemical remission, respectively; see Table: Changes in PCDAI/PUCAI Scores, Biochemical Remission, and Steroid-Free Remission.
• Three (60%) and 2 (40%) patients with UC had S0 and S1 disease severity, respectively, defined by PUCAI scores >65.
• CRP and PCDAI/PUCAI scores decreased in both clinical responders and non-responders, but the decrease was more in the clinical remission group (P=0.007 and P=0.371, respectively).
• Similarly, FCP levels and the need for corticosteroids after STELARA therapy significantly decreased in the clinical remission group (P=0.021 and P=0.014, respectively).

Endoscopic Remission to STELARA

• Endoscopy was performed on 4 patients with UC.
• MES scores for 3 patients with UC decreased from 3, 2, and 2 before STELARA to 1, 0, and 0 after treatment, respectively.

Safety Profile

• Among the 13 patients treated with STELARA, 2 reported infection related to treatment.
• One patient experienced acute Salmonella enteritis, which required hospitalization and IV antibiotics, whereas another patient developed cystitis.

Cohen et al (2024)³ conducted a retrospective cohort study to assess the effectiveness and safety of STELARA in children with UC and unclassified inflammatory bowel disease (IBDU).

Study Design/Methods

• This was a retrospective study from 16 centers affiliated with the Pediatric IBD Interest and Porto Groups of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN).
• Children and adolescents (≤18 years old) who received ≥1 dose of STELARA for UC or IBDU according to the revised Porto criteria and current guidelines were included.
• The primary outcome was corticosteroid-free clinical remission (CFR) following STELARA initiation over 52 weeks.
• Secondary outcomes included:
  • Clinical remission and response at 16 weeks
    • Clinical remission was defined as a PUCAI score of <10
    • Clinical response was defined as a reduction in PUCAI score of >20 points
  • CRP levels below 5 mg/L and FCP levels under 150 µg/g
    • Laboratory remission was defined as CRP levels below 5 mg/L and FCP levels below 150 µg/g
  • Endoscopic and radiologic remission
    • Radiologic remission was defined as complete remission on bowel ultrasound or magnetic resonance enterography.
    • Endoscopic remission was defined as an MES of 0 on colonoscopy during follow-up.
    • Endoscopic and radiologic remission were determined for the intention-to-treat (ITT) group, using nonresponse imputation for children who discontinued therapy during the follow-up period.
  • Disease exacerbation
    • Defined as a PUCAI score of ≥10
  • Hospitalizations
  • Need for IBD-related surgery during follow-up
  • Adverse events
• The induction dose ranged from 130 mg to 520 mg with a median dose of 6.1 mg/kg (IQR, 5.5-7.7).⁴
• Maintenance dosage regimens used were: 45 mg every 4, 6, or 8 weeks; 90 mg every 4, 6, 7, 8, or 12 weeks; or 130 mg every 4 weeks.⁴

Results

Baseline Characteristics

• There were 58 children in the study, with 39 (67.2%) diagnosed with UC; the median age at STELARA initiation was 14.5 years (IQR, 11.5-16.5) and median duration of follow-up was 12.8 months (IQR, 5.1-26.3).
• Prior to STELARA therapy, 50 (86.2%) children had received treatment with immunomodulators.
• All 58 children were treated with biologic agents:
  • 20 (34.5%) had failed 1 biologic agent
  • 28 (48.3%) had failed 2 biologic agents
  • 10 (17.2%) had failed 3 biologic agents
• The median PUCAI score at the initiation of STELARA therapy was 45 (IQR, 31.3-55).
• Twenty-three (39.7%) children underwent escalation of STELARA dosage during the follow-up period, with 13 (57%) achieving clinical or biomarker response.

Clinical and Biochemical Response to STELARA

• CFR was achieved in 27 (46.6%), 33 (56.9%), and 37 (63.8%) children at weeks 16, 26, and 52, respectively.
• Eighty-four percent of the children successfully weaned steroids within 3 months of STELARA initiation.
• Clinical remission was achieved in 29 (50%), 33 (56.9%), and 37 (63.8%) children at weeks 16, 26, and 52, respectively; clinical response was observed in 39 (67.2%) children at 16 weeks.
• Overall, CFR was achieved in 19/31 (57.6%) children receiving corticosteroid therapy at baseline vs 18/27 (66.7%) children not treated with corticosteroids (P=0.671).
• The variables associated with achieving CFR were:
  • Diagnosis of UC compared with IBDU (hazard ratio [HR], 2.24; 95% CI, 1.03-4.85; P=0.041)
  • Lack of prior vedolizumab therapy (HR, 2.18; 95% CI, 1.11-4.27; P=0.023)
  • History of corticosteroid-resistant disease (HR, 4.29; 95% CI, 1.58-11.65; P=0.004)
• Laboratory remission was achieved in 11 (19%), 16 (36.2%), and 25 (51.7%) children at weeks 16, 26, and 52, respectively.
• For longitudinal changes in laboratory parameters, see Table: Longitudinal Changes in Laboratory Parameters.

• Twenty-four (41.4%) children discontinued STELARA at a median duration of 5 [3.4-10.3] months after initiation. The reasons for discontinuation among children were, n (%):
  • Nonresponse: 21 (87.5)
  • Adverse events: 3 (12.5)
• Ten (41.7%) children underwent colectomy after discontinuation.
• Among the 6 (10.3%) children who underwent colectomy while on STELARA therapy, 3 had severe UC at STELARA initiation.
• Eleven (19%) children experienced IBD-related hospitalizations.
• Disease exacerbation occurred in 13 (37.1%) of children in remission.

Ustekinumab Serum Levels

• Ustekinumab serum levels were available for 22 (38%) children, with median (IQR) levels of 4.1 µg/mL (1.9-5.1), 2.7 µg/mL (1.6-6.8), and 2.6 µg/mL (2.1-5.4) at weeks 16, 26, and 52, respectively.
• None of the children showed evidence of antidrug antibodies.

Safety Profile

• Treatment-related adverse events were reported in 6 (10.3%) children, leading to STELARA discontinuation in 3 children and death in 1.
• These events included interstitial nephritis, hypersensitivity reaction, breast abscess, injection-site reaction, cytomegalovirus infection, and 1 death attributed to an acute episode of severe diarrhea in an adolescent male who was also on corticosteroids and methotrexate while on STELARA therapy.

Koudsi et al (2023)⁵ assessed the safety and efficacy of STELARA in a multicenter, retrospective study in pediatric patients with IBD using data from the Groupe d'Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID), a French consortium.

• This analysis included patients <18 years of age treated with ≥1 STELARA injection for CD or UC from January 2016 to December 2019 at 9 university hospitals.
• Clinical, biological, and endoscopic data were retrospectively collected. Additionally, the analysis was based on information from electronic medical records such as patient’s baseline characteristics, clinical data, clinical disease activity index, disease phenotype before starting STELARA, treatment history, endoscopic findings, and laboratory parameters at the beginning of the treatment (induction), 3 months after induction and at the last follow-up.
• All patients included in this study were resistant to anti-TNF agents.
• Patients received weight-adjusted STELARA IV (6 mg/kg) and 90 mg SC after 8 weeks.
• Of the 53 patients included in this analysis, 5 (9.4%) patients had UC.
• Significant improvements in PUCAI were observed at 3 months (mean, 25 [15-40]) and at the last follow-up (mean, 18.3 [0-35]) compared to baseline (mean, 47 [35-65]).
• The mean CRP at STELARA induction was 15.8 mg/L (0.5-30). At
  3 months, CRP normalization was observed in 75% of patients.
• Overall, STELARA was discontinued in 15/53 (28%) patients due to lack of efficacy in
  8 patients, loss of response in 5 patients, and exacerbation of an associated Chronic Recurrent Multifocal Osteomyelitis in 1 patient. The treatment was discontinued in the first 3 months in 7 patients and after 3 months in 8 patients.
• No severe adverse effects were reported in this analysis.

Patel et al (2021)⁶ conducted a retrospective chart review of the use of STELARA in pediatric patients with UC at a single center.

• Clinical remission and steroid-free remission at weeks 26 and 52 of therapy were the primary outcomes.
• Of the twelve patients evaluated, the cohort was mostly female (83%) and ages ranged from 6-15 years.
• By week 26, 78% (7/9) of patients achieved both clinical and steroid-free remission, and 87% (6/7) of these patients were on STELARA monotherapy.
• Five patients had data at week 52; of those, 80% (4/5) had clinical and steroid-free remission on STELARA monotherapy.
• At week 26, 88% of patients were on intensified therapy compared to adult dosing recommendations based on therapeutic drug monitoring and clinical decision making; at week 52, 100% of patients were on intensified therapy.
• No adverse effects were observed in this cohort.

Case Reports

Alhalabi (2023)⁷ reported the case of a 10-year-old male with steroid-refractory pancolitis treated with STELARA.

• Patient presented with mild abdominal pain and bloody nocturnal diarrhea (6-8 times), (PUCAI=55). Past medications included mesalamine and prednisone.
• STELARA was initiated as 260 mg (6 mg/kg) IV followed by 90 mg SC after 8 weeks (induction).
• The patient achieved clinical remission (PUCAI=10) after 8 weeks and STELARA 90 mg SC was administered with the next SC dose scheduled after 12 weeks.
• At week 26, patient presented with tachycardia, abdominal pain, and 6 episodes of bloody nocturnal diarrhea (PUCAI=75). A sigmoidoscopy revealed spontaneous bleeding and multiple ulcers. The patient was managed according to treatment guidelines and the STELARA maintenance SC dose was escalated to every 8 weeks.
• Assessment at week 52 revealed clinical remission (PUCAI=5), a partial Mayo score of 0, and FCP of 20 µg/g. Additionally, his weight increased from 34 kg (prior to STELARA treatment) to 43 kg.

Kakiuchi and Yoshiura (2022)⁸ reported the case of a 14-year-old male with moderately active UC treated with STELARA.

• Patient reported to the hospital with bloody stool and diarrhea for 4 months.
• Colonoscopy and pathologic findings were consistent with a diagnosis of total colitis-type UC (MES, 2; PUCAI, 50).
• After failing treatment with 5-aminosalicylic acid agents (5-ASAs), prednisolone, and azathioprine, he was started on infliximab. The patient achieved clinical remission and symptom control with treatment over a 15-month period with infliximab and resumption of prednisolone and azathioprine.
• After 17 months of treatment with infliximab, symptoms worsened, and treatment was discontinued due to secondary loss of response and antibody formation.
• STELARA was started when the patient was 16 years of age with a 260 mg IV dose on day 1 followed by 90 mg SC every 8 weeks.
• After 8 weeks, abdominal symptoms improved, and clinical remission was achieved at
  16 weeks (PUCAI, 5) and maintained during maintenance therapy.
• Endoscopic remission was achieved after 60 weeks of therapy.
• No adverse events were observed during treatment.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 17 June 2024.