SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• VOYAGE 1 and VOYAGE 2 have described the use of TREMFYA in patients with psoriasis (PsO) plaques on the palms and soles.^1-3
  • Improvement in PsO plaques on the palms and soles was evaluated by the Physician Global Assessment of hands and/or feet (hf-PGA; range from 0-4 [0=clear: no signs of PsO, postinflammatory hyperpigmentation may be present; 1=almost clear: pink coloration, minimal fine scaling; 2=mild: mild clearly distinguishable erythema, no thickening of skin, with mild scaling, with or without pustules; 3=moderate: dull-red erythema with moderate diffuse scaling, and some thickening of the skin, with or without fissures, with or without pustule formation; 4=severe: deep, dark-red erythema with severe diffuse scaling and thickening as well as numerous fissures, with or without pustule formation]).
• The G-PLUS study evaluated the efficacy and safety of TREMFYA in patients with moderate to severe nonpustular palmoplantar psoriasis (ppPsO).⁴

CLINICAL DATA

VOYAGE 1

Blauvelt et al (2017)¹ assessed improvement in PsO plaques on the palms and soles in the VOYAGE 1 trial, a phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study evaluating the efficacy and safety of TREMFYA compared to placebo and adalimumab in 837 patients with moderate to severe plaque PsO.

Study Design/Methods

• Adult patients (≥18 years of age) with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, and had a baseline Investigator’s Global Assessment (IGA) score ≥3, a Psoriasis Area and Severity Index (PASI) score ≥12, and ≥10% of their body surface area (BSA) involved were eligible for enrollment.
• The study comprised of a placebo-controlled period (week 0-16) and an active-comparator period (week 0-48).
• At week 16, patients randomized to placebo crossed over to receive TREMFYA through week 48.
• Eligible patients were randomized in a 2:1:2 ratio to 1 of 3 treatment arms.
  • TREMFYA 100 mg (n=329) at weeks 0, 4, 12 and every 8 weeks through week 44
  • Placebo (n=174) at weeks 0, 4, and 12 followed by TREMFYA 100 mg at weeks 16 and 20, and every 8 weeks through week 44
  • Adalimumab 80 mg (n=334) at week 0, 40 mg at week 1, and 40 mg every 2 weeks through week 47
• Improvement in PsO plaques on the palms and soles was evaluated by hf-PGA (range from 0-4 [0=clear: no signs of PsO, postinflammatory hyperpigmentation may be present; 1=almost clear: pink coloration, minimal fine scaling; 2=mild: mild clearly distinguishable erythema, no thickening of skin, with mild scaling, with or without pustules; 3=moderate: dull-red erythema with moderate diffuse scaling, and some thickening of the skin, with or without fissures, with or without pustule formation; 4=severe: deep, dark-red erythema with severe diffuse scaling and thickening as well as numerous fissures, with or without pustule formation]).³

Results

Baseline Patient Characteristics

• Baseline characteristics of PsO plaques on the palms and soles are noted in Table: Baseline Characteristics of PsO Plaques on the Palms and Soles - Randomized Patients in VOYAGE 1.

Efficacy

• The hf-PGA outcomes at weeks 16, 24, and 48 are noted in Table: hf-PGA Outcomes at Weeks 16, 24, and 48 - Randomized Patients in VOYAGE 1.
• The proportion of patients achieving hf-PGA 0/1 was significantly higher for TREMFYA vs placebo at week 16, and responses to TREMFYA were superior to adalimumab at week 24 and week 48.

VOYAGE 2

Reich et al (2017)² assessed improvement in PsO plaques on the palms and soles in the VOYAGE 2 trial, a phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study evaluating the efficacy and safety of TREMFYA compared to placebo and adalimumab in 992 patients with moderate to severe plaque PsO.

Study Design/Methods

• Adult patients (≥18 years of age) with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, and had a baseline IGA score ≥3, a PASI score ≥12, and ≥10% of their BSA involved were eligible for enrollment.
• The study comprised of a placebo-controlled period (week 0-16), an active comparator-controlled period (weeks 0-28), and a randomized withdrawal and retreatment period (weeks 28-72).
• Eligible patients were randomized in a 2:1:1 ratio to 1 of 3 treatment arms.
  • TREMFYA 100 mg (n=496) at weeks 0, 4, 12, and 20
  • Placebo (n=248) at weeks 0, 4, and 12 then TREMFYA at weeks 16 and 20
  • Adalimumab 80 mg (n=248) at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter through week 23
• At week 28:
  • Patients receiving TREMFYA who achieved a PASI 90 (responders) were rerandomized in a 1:1 ratio to TREMFYA or placebo, and upon loss of 50% or more of their week-28 PASI 90 response were retreated with TREMFYA, another dose 4 weeks later, then every 8 weeks thereafter. TREMFYA nonresponders continued TREMFYA treatment.
  • Placebo→TREMFYA responders received placebo every 8 weeks beginning at week 28, and upon loss of 50% or more of their week-28 PASI 90 response were retreated with TREMFYA, another dose 4 weeks later, then every 8 weeks thereafter. Placebo→TREMFYA nonresponders at week 28 continued TREMFYA every 8 weeks.
  • Adalimumab responders received placebo and upon loss of 50% or more of week-28 PASI 90 response, initiated TREMFYA, another dose 4 weeks later, then every 8 weeks thereafter, and adalimumab nonresponders initiated TREMFYA at week 28 (5 weeks after the last dose of adalimumab), another dose 4 weeks later, then every 8 weeks thereafter.
• Improvement in PsO plaques of the hands and soles was evaluated by hf-PGA.

Results

Baseline Patient Characteristics

• Baseline characteristics of PsO plaques on the palms and soles are noted in Table: Baseline Characteristics of PsO Plaques on the Palms and Soles - Randomized Patients in VOYAGE 2.

Efficacy

• Hf-PGA outcomes at weeks 16 and 24 are noted in Table: hf-PGA Outcomes at Weeks 16 and 24 - Randomized Patients in VOYAGE 2.
• Patients treated with TREMFYA achieved greater improvement in hf-PGA compared with placebo at week 16.
• Greater improvements in hf-PGA were observed at week 24 in patients receiving TREMFYA vs adalimumab.

G-PLUS

Passeron et al (2023)⁴ evaluated the efficacy and safety of TREMFYA in patients with moderate to severe nonpustular ppPsO in G-PLUS, a phase 3b, double-blind, placebo-controlled, multicenter, randomized clinical trial.

Study Design/Methods

• Adult patients (≥18 years of age) with a diagnosis of moderate to severe nonpustular ppPsO and limited overall skin involvement (3≤PASI<10) with at least 1 plaque at a body site other than the palms or soles present for ≥6 months.
• The study comprised of a placebo-controlled, double-blind period (weeks 0-16); an open-label active treatment period (weeks 16-48), with patients initially receiving placebo crossing over to receive TREMFYA at week 16; and a follow-up safety period (weeks 48-56).
• Eligible patients were randomized in a 2:1 ratio to:
  • TREMFYA 100 mg (n=78) at weeks 0, 4, and 12, and every 8 weeks thereafter through week 44
  • Placebo (n=39) at weeks 0, 4, and 12, followed by TREMFYA at weeks 16 and 20, and every 8 weeks thereafter through week 44
• Statistical comparisons between TREMFYA and the placebo groups were performed through week 16.
• The primary efficacy endpoint was the proportion of patients achieving a palmoplantar PASI (ppPASI) 75 response (≥75% improvement from the baseline in the ppPASI score) at week 16. Relevant secondary endpoints included changes from baseline of ppPASI, palmoplantar Investigator’s Global Assessment (ppIGA), and palmoplantar Quality-of-Life Instrument (ppQLI).
• Safety assessments were based on the safety analysis set, based on the trial treatment actually received.

Results

Baseline Patient Characteristics

• The full analysis set included 117 patients, of which, 78 patients received TREMFYA while 39 patients received placebo.
• Baseline patient characteristics can be found in Table: G-PLUS Demographics and Baseline Disease Characteristics.

Efficacy

• The ppPASI75 response at week 16 was achieved by 35.9% of the TREMFYA group compared with 28.2% in the placebo group (difference in response: 7.7%; 95% confidence interval: -11.5 to 24.7; P=0.533). The primary endpoint was not met.
• The primary endpoint and relevant secondary endpoints at week 16 can be found in Table: G-PLUS Primary Efficacy and Relevant Secondary Efficacy Endpoints at Week 16.

• Numerical improvements of ppPASI 75/90/100 and ppIGA 0/1 response with a ≥2-point reduction from baseline in ppIGA score were observed in patients receiving TREMFYA through week 48 as shown in Table: G-PLUS ppPASI and ppIGA Responses through Week 48.

Safety

• No new safety signals or adverse events (AEs) of special interest were identified.
• Through week 56:
  • Treatment-emergent AEs were reported in 87.2% (68/78) of TREMFYA patients and 56.4% (22/39) of the placebo-crossover patients.
  • Serious AEs were reported in 6.4% (5/78) of TREMFYA patients and 5.1% (2/39) of the placebo-crossover patients.
  • No events leading to death or cases of anaphylactic reaction/serum sickness, malignancy, inflammatory bowel disease, or active tuberculosis were observed.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted through 26 December 2024.

Summarized in this response are clinical trial data specific for patients receiving TREMFYA with PsO plaques on the palms and soles only.