SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A phase 3, multicenter, placebo (PBO)-controlled trial (PROTOSTAR) evaluated the efficacy, safety, pharmacokinetics (PK), and immunogenicity of TREMFYA in pediatric patients (≥6 to <18 years of age) with moderate to severe plaque psoriasis (PsO).¹
  • At week 16, in part 1, the co-primary endpoints of Investigator's Global Assessment (IGA) score of 0/1 were achieved by 66% of patients receiving TREMFYA compared to 16% of patients receiving PBO (P<0.001), and Psoriasis Area Severity Index (PASI) 75 was achieved by 76% of patients receiving TREMFYA compared to 20% of patients receiving PBO (P<0.001).
  • The United States Food and Drug Administration (US FDA) co-primary endpoint of PASI 90 (instead of PASI 75) at week 16 was achieved by 56% of patients receiving TREMFYA compared to 16% of patients receiving PBO (P=0.003).
  • Additional efficacy data were also reported from parts 1 and 2 through week 52.
  • For safety through week 16, 42% of patients receiving TREMFYA and 68% of patients receiving PBO reported adverse events (AEs).
  • Through week 52, rates and types of AEs among patients treated with TREMFYA were reported as similar in parts 1 and 2.
• Case reports describing the use of TREMFYA in pediatric patients with plaque PsO are reported.^2,3

CLINICAL DATA

Phase 3 Clinical Study - PROTOSTAR

Prajapati et al (2024)¹ evaluated the efficacy, safety, PK, and immunogenicity of TREMFYA compared to PBO with an open-label reference arm (etanercept) in a phase 3, multicenter, randomized trial in pediatric patients with moderate to severe plaque PsO.

Study Design/Methods

• Select inclusion criteria:
  • Pediatric patients (≥6 to <18 years of age) with moderate to severe plaque PsO for ≥6 months (with or without psoriatic arthritis)
  • IGA ≥3
  • PASI ≥12, and ≥10% body surface area (BSA) involvement, with at least 1 of the following criteria fulfilled:
    • Very thick lesions
    • Clinically relevant facial, genital, or hand/foot involvement
    • PASI ≥20 or BSA >20% or IGA=4
  • PsO inadequately controlled by phototherapy and/or topical therapy
• Select exclusion criteria:
  • Non-plaque or drug-induced PsO
  • History of chronic/recurrent infectious diseases or lymphoproliferative diseases
  • Previous treatment with TREMFYA or etanercept
  • Anti-tumor necrosis factor (TNF)α therapies within 3 months.
  • Interleukin (IL)-12/23, IL-17, or IL-23 therapies within 6 months
  • Systemic immunosuppressants within 4 weeks
  • Systemic or topical therapies affecting PsO or IGA within 2 weeks
• Adolescents (≥12 to <18 years of age) were randomized 2:1:1 in part 1a to 1 of 3 treatment arms shown in Figure: PROTOSTAR Study Design.
• Children (≥6 to <12 years of age) were randomized 1:1:1 in part 1b to receive TREMFYA, PBO or etanercept, which began after adolescents in part 1a completed the PBO-controlled period (weeks 0-16).
• Dosing in part 1 was double-blinded, TREMFYA and PBO were administered as subcutaneous (SC) injections at weeks 0, 4, and 12 based on body weight (<70 kg, 1.3 mg/kg; ≥70 kg, 100 mg).
• Etanercept was administered SC weekly (0.8 mg/kg up to 50 mg/dose) through week 15 (no statistical comparisons between the etanercept and TREMFYA arms were planned in the study).
• Part 2 evaluated adolescents receiving TREMFYA from weeks 0-52 in an open label, single-arm design.

Results

Patient Demographics

Part 1

• A total of 92 patients were randomized to receive TREMFYA (n=41), PBO (n=25), and etanercept (n=26).¹
  • Among the randomized groups, 62 (67%) patients were adolescents and 30 (33%) were children, respectively. For baseline characteristics, see Table: Select Baseline Characteristics (Full Analysis Set).
  • Through week 52, 79 (86%) of patients remained in the study.

Part 2

• A total of 28 adolescents received open-label TREMFYA, with 27 (96%) patients continuing treatment through week 52. For baseline characteristics, see Table: Select Baseline Characteristics (Full Analysis Set).¹

Efficacy

Part 1: PBO-Controlled Period (weeks 0-16) - TREMFYA vs PBO

• For co-primary and major secondary endpoints, see Table: Co-Primary and Major Secondary Endpoints at Week 16.⁴ 

• For clinical response rates among children and adolescents, see Table: Clinical Response Rates at Week 16 by Age Group.¹

Part 1: Open-label Reference Arm (etanercept)

• At week 16, 69%, 69% and 54% of patients receiving open-label etanercept achieved IGA 0/1, PASI 75 and PASI 90, respectively.¹

Part 1 (weeks 16-52) - Crossover to TREMFYA

• A total of 80% (20/25) of patients randomized to the PBO group who were PASI 90 nonresponders at week 16 were crossed over to the TREMFYA group.¹
  • The response rates for IGA 0/1, PASI 75 and PASI 90 were 0%, 5%, and 0%, respectively at week 16, and improved to 80%, 95%, and 65%, respectively at week 52.
• A total of 85% (22/26) of patients randomized to receive open-label etanercept were crossed over to receive TREMFYA at week 20.¹
  • The response rates for IGA 0/1, PASI 75, and PASI 90 were 64%, 55%, and 36%, respectively at week 20, and improved to 91%, 96%, and 91%, respectively at week 52.

Part 1 (weeks 16-52) – PASI 90 Nonresponders Treated with TREMFYA

• At week 16, 44% (18/41) of patients in the TREMFYA group who were PASI 90 nonresponders continued TREMFYA treatment, and 61% (11/18) of patients achieved PASI 90 by week 52.¹

TREMFYA Withdrawal and Retreatment in PASI 90 Responders

• Of the 41 patients randomized to receive TREMFYA, 23 (56%) patients achieved PASI 90 at week 16 and were withdrawn from TREMFYA; 30% of these patients maintained a PASI 90 response at week 52.¹
• Four patients met retreatment criteria after loss of PASI 90 response and were retreated at either week 44 or week 48. One patient regained PASI 90 response at week 52.¹

Part 2: Open-Label TREMFYA (weeks 0-52)

• At week 16, 89%, 82%, and 64% of patients achieved IGA 0/1, PASI 75, and PASI 90, respectively; 46% and 36% of patients achieved IGA 0 and PASI 100, respectively.¹
• The response rates by week 52 for IGA 0/1, PASI 75, PASI 90, IGA 0 and PASI 100 were 86%, 93%, 82%, 75% and 54%, respectively.¹
• At week 52, the mean (standard deviation) change from baseline in the CDLQI score was -7.3 (6.8).¹

Safety

Part 1: PBO-Controlled Period (weeks 0-16)

• Through week 16, 42% of patients receiving TREMFYA, 68% of patients receiving PBO and 58% of patients receiving ETN reported AEs (see Table: AEs Occurring in Patients from Part 1 in the TREMFYA, PBO and Open-Label ETN Groups through Week 16).¹
• One patient in the PBO group discontinued treatment due to worsening PsO, compared to 0 patients in the TREMFYA group.¹
• At least 1 serious adverse event (SAE) was reported in the TREMFYA group (radius fracture) and was unrelated to study treatment.¹
• One patient in both the TREMFYA and PBO groups reported mild injection site reactions (ISRs).¹
• One patient treated with etanercept reported ISRs.¹

Parts 1 and 2: through Week 52

• Rates and types of AEs among patients treated with TREMFYA through week 52 were reported as similar in parts 1 and 2 (see Table: AEs Occurring in >5% of Patients in the Total TREMFYA Group from Part 1 and 2 at Week 52).¹
• Three SAEs were reported through week 52, however none were related to study treatment.¹
• Through week 52, 2% and 7% of patients receiving TREMFYA reported ISRs in part 1 and part 2, respectively, which were deemed as mild.¹

Case Reports

Song EJ et al (2021)² described a case of a 13-year-old female from Guatemala with no known medical or family history who presented with widespread plaque PsO (BSA involvement of 12% and static IGA 3).

• No sufficient plaque PsO improvement was seen with prior ultrapotent topical steroids and methotrexate (MTX) treatment.
• Patient tested positive for hepatitis B surface antigen, hepatitis B core antibodies, and hepatitis B envelope antibodies, but negative for hepatitis B envelope antigen and hepatitis B surface antibodies.
• Hepatitis B virus deoxyribonucleic acid (DNA) load was 3.4 IU/mL (log 10).
• Liver function tests (aspartate aminotransferase [AST], 24 U/L; alanine aminotransferase [ALT], 23 U/L) and alpha-fetoprotein were in normal ranges.
• Ustekinumab 45 mg SC and entecavir 0.5 mg daily were initiated.
• Six weeks after initiation of ustekinumab, a slight increase in liver enzymes (AST, 51 U/L; ALT, 77 U/L) and decrease in viral load (2.4 IU/mL [log 10]) were seen with no reported or observed abdominal pain, jaundice, itching, or flu-like symptoms.
• At the 28-week follow-up with treatment of ustekinumab, the patient presented to a dermatologist with a 7% BSA involvement and an IGA 3 and was then switched to TREMFYA 100 mg SC.
• Following 1 dose of TREMFYA (4-week follow-up), the patient had 3% BSA and an IGA 3.
• After 12 weeks of TREMFYA treatment, the patient had 1% BSA with an IGA 2. Her liver enzymes remained stable (AST, 26 U/L; ALT, 42 U/L) and viral load was undetectable.

Kim et al (2019)³ described a case of a 12-year-old female patient who presented with a 6-month history of plaque PsO.

• Minimal improvement was achieved with prior treatment of medium- and high-potency topical steroids.
• Narrow-band ultraviolet B phototherapy had been discontinued due to difficulty in attending treatment sessions.
• On physical exam, she presented with diffuse pink-red scaly plaques involving the scalp, forehead, trunk, buttocks, and upper and lower extremities involving >50% BSA with a PASI 31.
• Additionally, she had pitting of multiple fingernails but no dactylitis or joint swelling.
• Treatment was initiated with MTX 15 mg (0.4 mg/kg) weekly with minimal response seen at 4 months.
• She was switched to adalimumab treatment for 10 weeks, followed by ustekinumab treatment for 16 weeks, both without improvement.
• MTX was reinstituted at 20 mg weekly (0.3 mg/kg, given interval weight gain).
• TREMFYA 100 mg SC at weeks 0 and 4, then q8w was added to MTX treatment after initial screening labs were all within normal ranges.
• Her plaques started to thin as early as week 4, and given the improvement at week 8, MTX was decreased to 10 mg (0.16 mg/kg) weekly.
• At 5 months, most plaques had resolved with postinflammatory hyperpigmentation. Her PASI score was reduced to 1 and MTX continued to be tapered.
• No AEs or laboratory abnormalities during TREMFYA treatment were reported.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 March 2025.