Summary

• Please refer to the local labeling for relevant information on approved indications, dosage, and administration of STELARA.
• The extrapolation analysis to support the use of STELARA in pediatric patients with juvenile psoriatic arthritis (jPsA) is described below.¹
• Data from Ustekinumab Pediatric Opportunistic Pharmacokinetics Study (U-POPS), a phase 1, real-world, open-label study evaluating the pharmacokinetics (PK) and safety of STELARA in pediatric patients with jPsA, is summarized below.^2,3 

CLInical data

Extrapolation Analysis

Leu et al (2022)¹ described the pharmacokinetic, clinical response, and safety analyses that supported the use of STELARA in jPSA (>6 years old) by extrapolating data from pediatric patients with PsO in these studies and from phase 3 randomized controlled trials of STELARA in adults with PsO or PsA.

Study Design/Methods

• Data employed in the analyses were derived from the following clinical trials:
  • CADMUS: A phase 3, randomized, placebo-controlled trial that evaluated the use of STELARA in 110 adolescent patients (aged ≥12 to <18 years) with psoriasis (PsO), including patients with jPsA, at the standard or half-standard subcutaneous dosing regimen at weeks 0 and 4 and then every 12 weeks (q12w).
  • CADMUS Jr: A phase 3, open-label study that assessed the PK, efficacy, and safety of STELARA in 44 patients with PsO who were aged ≥6 to <12 years, including patients with jPsA, at the standard subcutaneous dosing regimen at weeks 0 and 4 and then q12w.
  • PSUMMIT-1 and PSUMMIT-2: Phase 3, randomized, placebo-controlled trials that evaluated the use of STELARA (45 or 90 mg subcutaneously [SC] at weeks 0, 4, and then q12w) in 615 and 312 adult patients with PsA, respectively.
  • PSTELLAR: A phase 3, randomized, controlled trial that evaluated STELARA
    (45 or 90 mg SC at weeks 0, 4, 16, and then q12w up to every 24 weeks) in 478 adult patients with PsO.
• Data from pediatric patients who received the standard dosing regimen for STELARA (≤60 kg, 0.75 mg/kg; >60 to ≤100 kg, 45 mg; >100 kg, 90 mg) from the above clinical trials were included in the analyses because the demonstrated drug exposure in these pediatric patients was comparable to adults who received STELARA 45 mg.

Exposure Matching for STELARA for jPsA

• The CADMUS and CADMUS Jr trials, among the patients with PsO, included 7 patients with jPsA. Data from patients with jPsA were descriptively compared with data from adults with PsA (PSUMMIT-1).
  • Of the 7 patients with jPsA, 4 received the STELARA standard dosage.
  • The STELARA steady-state trough concentration (C_trough,ss) through week 52 in these 4 patients was compared as follows:
    • CADMUS and CADMUS Jr who received the standard adult dosage.
    • Excluding patients with jPsA.
    • Adults with PsA from PSUMMIT-1 who received the standard dosage.

Response Analyses for STELARA for jPsA

• Response rates for achievement of ≥75% improvement in Psoriasis Area and Severity Index (PASI; PASI 75) score, ≥90% improvement in PASI (PASI 90), and 100% improvement in PASI (PASI 100) in patients with jPsA who received the standard adult STELARA dosage in CADMUS and CADMUS Jr were descriptively compared with those in adults with PsA who received the standard dosage in PSUMMIT-1.

Safety Analyses for STELARA for jPsA

• Safety was extrapolated from the established safety profile of STELARA in the 154 pediatric patients with PsO in CADMUS and CADMUS Jr, including 7 patients who also had jPsA.
• Adverse events (AEs) were monitored through weeks 60 and 56 in the CADMUS and CADMUS Jr studies, respectively.

Results

PK Matching for STELARA for jPsA

• Among pediatric patients who received similar STELARA dosage in CADMUS and CADMUS Jr, serum ustekinumab concentrations over time in pediatric patients who had PsO with jPsA were comparable with patients who had PsO without jPsA.
• PK exposures over time in pediatric patients who had PsO with and without jPsA were comparable with adults who had PsA (PSUMMIT-1). See Figure: Observed Serum Ustekinumab C_trough,ss Through Week 52 in Adult Patients with PsA (PSUMMIT-1) and Pediatric Patients with PsO with and without jPsA (CADMUS and CADMUS Jr).

Response Analyses for STELARA for jPsA

• PASI 75 response rates were comparable between 4 pediatric patients with PsO and jPsA who received standard STELARA dosage and adults with PsA (PSUMMIT-1). See Figure: PASI 75 Response Rates Through Week 52 in Pediatric Patients with PsO and jPsA (CADMUS and CADMUS Jr) and Adult Patients with PsA (PSUMMIT-1).
  • PASI 90 and PASI 100 response rates were also generally similar between these patient populations.

Safety Analyses for STELARA for jPsA

• No new safety signals were observed in the 7 patients with PsO and jPsA who received standard or half-standard STELARA dosage in the CADMUS or CADMUS Jr trials.
  • Six patients reported ≥1 AE.
  • No serious adverse events (SAEs) were reported.
• The similarity in safety profiles between pediatric patients with PsO and jPsA is supported by the comparable safety profiles observed in phase 3 clinical trials in adults with PsO and adults with PsA who received similar STELARA dose regimens.

Phase 1 Study

Bishop et al (2024)³ evaluated the PK and safety of STELARA in pediatric patients with jPsA in U-POPS, a real-world, open-label study.

Study Design/Methods

• Eligible patients were ≥5 to <18 years of age with jPsA and/or ≥6 to <18 years of age with PsO who had been receiving STELARA for ≥16 weeks and received ≥3 doses.
• Pediatric patients with PsO were used as the internal control group to compare with previously evaluated PsO PK data.
• The maximum study duration was approximately 16 weeks per patient, with 3 study visits (including a PK draw at each visit [≥7 days apart]) and an additional study visit for a fourth PK draw if the patient agreed.
• The primary endpoint was observed ustekinumab concentrations over an every-12-week dosing interval to compare against model-predicted median concentrations using a previously developed adolescent and pediatric patients with PsO population PK model.

Results

• A total of 31 patients (jPsA=11; pediatric PsO=20) were included in the study.
  • Of the 11 patients with jPSA, 81.8% had PsO.
• The baseline characteristics of patients with jPsA and pediatric patients with PsO are presented in Table: Select Baseline Characteristics.

• The median (range) total STELARA dose received for all patients was 45 mg (18-80 mg) administered q12w.
• A total of 100 ustekinumab PK samples were collected from patients with jPsA (n=34) and pediatric patients with PsO (n=66).
• Ustekinumab concentrations and time profiles were similar between patients with jPsA and pediatric patients with PsO. See Figure: Ustekinumab Concentration Versus Time Since Last Dose for All Patients (A) and by Weight-based Doses (B)

• Eight patients (25.8%) reported treatment-emergent adverse events (TEAEs) (jPsA, n=1; pediatric PsO, n=7) with no deaths, serious TEAEs, serious infections, malignancies, injection site and/or hypersensitivity reactions reported. No TEAEs leading to study discontinuation were noted.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 November 2024.