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FDA Approves Ustekinumab for Pediatric Patients Aged 2 Years and Older With Moderately to Severely Active Ulcerative Colitis
1-Minute Summary
The US Food and Drug Administration (FDA) has approved ustekinumab (Stelara; Janssen) injection for the treatment of moderately to severely active ulcerative colitis (UC) in pediatric patients aged 2 years and older. This regulatory milestone follows the agentโs April approval for pediatric Crohn disease (CD), establishing ustekinumab as the first nonโtumor necrosis factor (TNF)-targeting monoclonal antibody indicated for both major forms of pediatric inflammatory bowel disease (IBD).
The regulatory clearance was supported by pharmacokinetic and safety data from adult UC and pediatric CD trials, alongside data from the 52-week UNIFI Jr. clinical trial of 112 pediatric patients aged 3 to 17 years. Among the 79 children who achieved clinical response at week 8 following a single intravenous (IV) induction dose, 40.5% attained clinical remission at week 52, and 40.5% remained corticosteroid-free for at least 90 days. Remission rates were substantially higher in biologic-naive patients compared with those who had prior biologic treatment failure (47.2% vs 26.9%).
Why This Matters
Pediatric ulcerative colitis often follows an aggressive clinical course, requiring therapies that induce and sustain remission while avoiding long-term systemic corticosteroid exposure, which can severely compromise linear growth and bone mineral density. Historically, biologic options for children have been largely confined to anti-TNF agents. When patients develop loss of response, secondary failure, or adverse reactions to anti-TNF therapies, subsequent evidence-based options have been severely limited. As the first interleukin (IL)-12/23 inhibitor approved across both pediatric UC and CD, ustekinumab addresses a critical therapeutic void in pediatric gastroenterology.
Study at a Glance
| Feature | Details |
| Study Type | Open-label, multicenter, 52-week clinical trial (UNIFI Jr.) integrated with extrapolated pharmacokinetic/safety modeling from adult UC and pediatric CD trials |
| Participants | 112 pediatric patients aged 3 to 17 years (median age, 14 years; 54.5% female; 60.7% biologic-naive) with moderately to severely active ulcerative colitis |
| Intervention | Single weight-tiered intravenous (IV) induction dose of ustekinumab followed by maintenance therapy |
| Comparator | Baseline clinical parameters / stratified by prior biologic exposure status (biologic-naive vs prior biologic failure) |
| Primary Outcome | Clinical response at week 8; long-term clinical remission, mucosal healing, and corticosteroid-free remission at week 52 |
| Main Finding | 79 of 112 patients achieved clinical response at week 8; among responders, 40.5% achieved clinical remission, 65.8% were in symptomatic remission, and 40.5% achieved corticosteroid-free status at week 52 |
| Follow-up | 52 weeks |
What the Researchers Found
In the UNIFI Jr. cohort of 112 pediatric patients, an initial intravenous induction dose produced an initial clinical response in 79 patients by week 8. Evaluation of these 79 responders through the 52-week maintenance period demonstrated sustained clinical, endoscopic, and histologic benefits.
Table 1. Clinical and Endoscopic Endpoints at Week 52 Among Week 8 Responders ($n = 79$)
| Outcome Measure | Percentage of Responders (n=79) |
| Symptomatic Remission | 65.8% |
| Clinical Remission | 40.5% |
| Endoscopic Improvement | 40.5% |
| Corticosteroid-Free Status ($\ge$90 Consecutive Days) | 40.5% |
| Histologic-Endoscopic Mucosal Improvement | 36.7% |
Table 2. Week 52 Clinical Remission Stratified by Prior Biologic Exposure
| Patient Subgroup | Week 52 Clinical Remission Rate |
| Biologic-Naive Patients | 47.2% |
| Prior Biologic Failure | 26.9% |
The investigators concluded:
โUstekinumab induction and maintenance therapy was effective in treating pediatric patients aged 2 to [younger than] 18 years with moderate to severe pediatric UC.โ
Regarding the therapy’s overall safety profile, the study authors affirmed:
โUstekinumab was well-tolerated with no new safety signals.โ
Clinical Significance
- Mechanism of Action: By selectively targeting the p40 subunit shared by IL-12 and IL-23, ustekinumab inhibits pro-inflammatory cytokine signaling pathways distinct from the TNF-alpha cascade.
- Corticosteroid Sparing: Achieving corticosteroid-free remission for at least 90 days in 40.5% of responders represents a key therapeutic advantage, helping mitigate steroid-induced growth failure, osteopenia, and metabolic complications in children.
- Line of Therapy Considerations: While efficacy was observed across both biologic-naive and biologic-experienced cohorts, response was approximately 20 percentage points higher in biologic-naive individuals (47.2% vs 26.9%), emphasizing the prognostic value of early, effective biologic initiation.
Limitations
- Enriched Responder Analysis: Week 52 efficacy outcomes were reported specifically among the subgroup of patients who achieved clinical response at week 8 ($n = 79$), rather than the entire intent-to-treat (ITT) induction population ($N = 112$).
- Trial Cohort Demographics: The UNIFI Jr. trial enrolled patients aged 3 to 17 years (median age, 14 years), meaning clinical data specifically for patients aged 2 to younger than 3 years were largely extrapolated from pharmacokinetic modeling and safety registries in pediatric Crohn disease and adult populations.
- Lack of Direct Active Comparator: The single-arm design of the pediatric trial did not compare ustekinumab head-to-head with standard-of-care anti-TNF inhibitors or other alternative biologic mechanisms.
What Doctors Should Know
- Indication Scope: Ustekinumab is now FDA-approved for pediatric patients aged 2 years and older with moderately to severely active ulcerative colitis as well as moderately to severely active Crohn disease.
- Adverse Event Profile: According to the FDA, the most frequently observed adverse reactions in this pediatric population include:
- Nasopharyngitis and sinusitis
- Headache
- Abdominal pain and nausea
- Diarrhea
- Influenza and fever
- Fatigue
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- Pre-Treatment Screening: As with adult protocols, clinicians should ensure patients are screened for latent tuberculosis and evaluated for active infections before initiating ustekinumab therapy. Routine monitoring of symptoms, inflammatory markers, and endoscopic or fecal biomarkers should accompany maintenance administration.
Bottom Line
Ustekinumab expands the pediatric IBD armamentarium as the first non-TNF-targeting biologic approved for both Crohn disease and ulcerative colitis in children as young as 2 years old, demonstrating robust clinical and corticosteroid-free remission through 52 weeks with an established safety profile.
Original Research / DOI
- Data derived from the FDA approval announcement and the UNIFI Jr. pediatric clinical trial (Janssen Research & Development).
