SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Available data from post hoc analyses of DISCOVER-1, DISCOVER-2, VOYAGE 1, and VOYAGE 2 phase 3 clinical trials in adult patients with psoriatic disease evaluating the impact of TREMFYA on inflammatory biomarkers associated with an increased risk of cardiovascular (CV) events are summarized below.^1-6 

clinical DATA

Phase 3 Studies

Merola et al (2024)¹ reported post-hoc analyses results from 4 phase 3 studies (DISCOVER-1, DISCOVER-2, VOYAGE 1, and VOYAGE 2) evaluating the impact of TREMFYA on the neutrophil-to-lymphocyte ratio (NLR), a biomarker associated with CV risk, in adult patients with psoriatic disease.

Study Design/Methods

• DISCOVER-1 and DISCOVER-2 include patients with active psoriatic arthritis (PsA) who had a current diagnosis or a history of plaque psoriasis (PsO).
• A total of 1120 patients (DISCOVER-1, [n=381]; DISCOVER-2, [n=739]) were randomized in a 1:1:1 ratio to receive TREMFYA 100 mg subcutaneous (SC) at
  w (week) 0, w4, and then every 4 weeks (Q4W; N=373); TREMFYA 100 mg SC at w0, w4, and then every 8 weeks (Q8W; N=375); or placebo (PBO) at w0 to w20 Q4W, and then switched to TREMFYA 100 mg SC Q4W at w24 (N=372).
  • Inclusion criteria (DISCOVER-1): patients with tender joint counts (TJC) ≥3, swollen joint counts (SJC) ≥3, and C-reactive protein (CRP) ≥0.3 mg/dL.
  • Inclusion criteria (DISCOVER-2): biologic-naïve patients with TJC ≥5, SJC ≥5, CRP ≥0.6 mg/dL.
  • In both trials, approximately 90% of patients were biologic-naïve.
• VOYAGE 1 and VOYAGE 2 include patients with moderate to severe plaque PsO who were candidates for phototherapy and systemic therapy.
• A total of 1829 patients (VOYAGE 1, [n=837]; VOYAGE 2, [n=992]) were randomized in a 2:1 ratio to receive TREMFYA 100 mg SC at w0, w4, then Q8W (N=825) or PBO at w0, w4, w12 with PBO crossover to TREMFYA 100 mg SC at w16, w20 and Q8W thereafter (N=422).
  • Inclusion criteria: patients with plaque PsO who had Investigator’s Global Assessment (IGA) score of ≥3, psoriasis area and severity index (PASI) score ≥12, body surface area (BSA) ≥10%
  • Approximately 80% of patients from these two studies were biologic-naïve.
• This analysis included a total of 1061 patients (TREMFYA Q8W, [n=619]; PBO, [n=442]) with baseline NLR ≥2.5 (subgroup analyses: elevated NLR, 2.5 to <3.5; high NLR, ≥3.5).
• The analysis evaluated the following outcomes:
  • Least squares mean (LSM) changes in NLR from baseline through w48
  • Proportions of patients attaining NLR <2.5 (associated with no increased CV risk) through w48 or w100
  • Observed mean values from baseline through w100 for these CV risk factors (systolic blood pressure [SBP], diastolic blood pressure [DBP], and body mass index [BMI]).

Results

• Of the 1992 randomized patients, 53% had baseline NLR ≥2.5 (elevated, 57%; high, 43%). Eighty-three percent of patients with elevated/high CV risk were biologic-naïve.
• A higher proportion of patients were randomized to TREMFYA Q8W: PBO in PsO (2:1) vs PsA (1:1) trials.
• Patients receiving TREMFYA experienced significant reductions in NLR compared to PBO from w4 through w16, regardless of baseline NLR-defined CV risk category or prior biologic experience. See Figure: Change in NLR From Baseline Over Time.
  • Reductions in NLR were sustained through 1 year (the total cohort) and 2 years (biologic-naïve cohort).

• Higher proportions of patients receiving TREMFYA achieved NLR <2.5 by w4/w8 through w16, despite prior biologic experience.
  • In biologic-naïve patients with elevated/high CV risk at baseline, rates of achieving NLR <2.5 from w16 (42%/28%) to W100 (49%/40%), respectively.
• Kavanaugh et al (2023)^2,7 reported post-hoc analyses results of the DISCOVER-1 and DISCOVER-2 trials evaluating the effect of TREMFYA on inflammatory biomarkers associated with an elevated risk of cardiovascular events (high-sensitivity C-reactive protein [hsCRP] and NLR) and its efficacy and safety in adult patients with active PsA and concurrent CV risk factors.

Study Design/Methods

• Patients with active PsA who had a current or documented history of PsO were eligible for the study.
  • Inclusion criteria (DISCOVER-1, N=381): patients with tender joint counts (TJC) ≥3, swollen joint counts (SJC) ≥3, and C-reactive protein (CRP) ≥0.3 mg/dL.
    • Approximately 31% of patients previously received 1-2 tumor necrosis factors.
  • Inclusion criteria (DISCOVER-2, N=739): patients were naïve to biologic agents and Janus Kinase (JAK) inhibitor with TJC ≥5, SJC ≥5, CRP ≥0.6 mg/dL.
• Patients were randomized 1:1:1 to receive TREMFYA 100 mg SC at w0, w4, and then Q4W, TREMFYA 100 mg SC at w0 and w4, then Q8W, or PBO Q4W with PBO crossover to TREMFYA 100 mg SC Q4W at w24.
• Patients included in this analysis had ≥1 of the following CV risk factors:
  • Obesity (BMI ≥30 kg/m²)
  • Smoking (past or current history)
  • History of hypertension (HTN), diabetes mellitus (DM), or hyperlipidemia.
• Achievement of endpoints at w24 (missing data was imputed as no response) was compared between TREMFYA and PBO groups with logistic regression adjusting for baseline levels, prior TNFi use, baseline disease-modifying antirheumatic drug (DMARD) use with nominal p-value reported.
• The trials evaluated endpoints as follows:
  • Key endpoints at w24:
    • American College of Rheumatology (ACR) response criteria (ACR20/ACR50/ACR70) improvement from baseline
    • Disease activity (DA) in PsA (DAPSA) low DA (LDA) score ≤14
    • Psoriasis Area and Severity Index (PASI) response (PASI 90/ PASI 100) improvement from baseline
    • IGA response score of 0/1
    • Dactylitis and enthesitis resolution: dactylitis severity score (DSS) and Leeds enthesitis index (LEI) score of 0, respectively
    • Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) response ≥4 points improvement from baseline
    • Health Assessment Questionnaire Disability Index (HAQ-DI) response ≥0.35 points improvement from baseline
    • PsA Disease Activity score (PASDAS) LDA score ≤3.2
    • Minimal Disease Activity (MDA) achievement of ≥5 from 7 criteria
  • The mean/median values at baseline of hsCRP and NLR
    • High risk of CV event: hsCRP>10 mg/L4 and NLR >2.5
  • The incidence of major adverse CV events (MACE): CV death, nonfatal myocardial infarction, or nonfatal stroke.

Results

• A total of 1120 patients were included in the analysis: 758 (68%) patients had ≥1 CV risk factor. Of these patients, 448 (59%) were obese, 420 (55%) had HTN, 315 (42%) were smokers, 171 (23%) had hyperlipidemia, and 103 (14%) had DM.⁷ 
• Among patients with ≥1 CV risk factor, TREMFYA significantly reduced hsCRP and NLR levels compared to PBO through w24 (TREMFYA 100 mg Q4W vs PBO, P<0.01; TREMFYA 100 mg Q8W vs PBO, P<0.0001). See Figure: hsCRP and NLR in TREMFYA vs PBO in PsA patients with ≥1 CV risk factor.

Kavanaugh et al (2023)³ reported post-hoc analysis results from DISCOVER-2 to assess the effect of TREMFYA on biomarkers of inflammation and CV risk (NLR and hsCRP) in biologic-naïve adult patients with active PsA through w112.

Study Design/Methods

• Patients with active PsA who were naïve to biologic agents and JAK inhibitors with a current or history of PsO, TJC ≥5, SJC ≥5, and CRP ≥0.6 mg/dL were eligible for the study.
• A total of 739 patients were randomized into a 1:1:1 ratio to receive TREMFYA 100 mg SC Q4W, TREMFYA 100 mg SC at w0 and w4, then Q8W, or PBO Q4W crossover to TREMFYA 100 mg SC Q4W at w24.
• This analysis included patients who had baseline NLR values >2.5 (the high NLR group) or baseline hsCRP levels >10 mg/L (the high hsCRP group).
• The study assessed the following outcomes:
  • LSM changes from baseline through w100 in NLR and hsCRP
  • Mean NLR and hsCRP levels at w0, w24, w52, and w100
  • Proportions of high NLR and high hsCRP cohorts achieving NLR ≤2.5 and hsCRP ≤10 mg/L through w100
  • SBP, DBP, and BMI through w100 were assessed using descriptive statistics.

Results

• A total of 445 patients were included in the high NLR cohort and 393 patients in the high hsCRP cohort, respectively.
  • Approximately 60% of patients in the high NLR group met the criteria for the high hsCRP group.
• Upon adjusting for baseline values of NLR, or hsCRP, and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs), patients receiving TREMFYA exhibited significantly greater reductions compared with PBO in both NLR and hsCRP from w4 through w24 with sustained reductions across 2 years. See Figure: LSM Changes and Mean NLR Through W100

• TREMFYA showed significantly higher proportions of high CV-risk patients who achieved NLR ≤2.5 compared to PBO by w24 and maintained the rate through w100. See Figure: LSM Changes and Mean hsCRP Levels Through W100.

Kirby et al (2023)⁴ conducted a post-hoc analysis of the VOYAGE 1 and VOYAGE 2 clinical trials to evaluate the changes in NLR over time in adult patients receiving TREMFYA and to determine whether NLR was associated with PsO severity.

Study Design/Methods

• Patients with moderate-to-severe PsO who had IGA score of ≥3, PASI score of ≥12, and BSA of ≥10% for at least 6 months and were candidates for systemic therapy or phototherapy were eligible for the study.^5,6
  • Pearson correlation coefficients (r) were calculated for baseline values and changes from baseline to w16 for NLR vs PASI in patients with both PASI and NRL data available.

Results

• In VOYAGE 1, at w16, the median NLR changes were -0.21 and +0.01 for patients receiving TREMFYA (n=317) and PBO (n=161), respectively.
• In VOYAGE 2, at week 16, the median NLR changes were -0.36 and -0.05 for patients receiving TREMFYA (n=470) and PBO (n=227), respectively.
• A nominally significant correlation between NLR and PASI was observed in patients treated with TREMFYA:
  • At baseline: VOYAGE 1, r=0.115 (P=0.037) and VOYAGE 2, r=0.140 (P=0.002).
  • Changes in NLR and PASI from baseline to week 16: VOYAGE 1, r=0.179 (P=0.001) and VOYAGE 2, r=0.161 (P=0.001).

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 21 April 2025.