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TREMFYA® (guselkumab)
Medical Information
TREMFYA - Effect on Inflammatory Cardiovascular Risk Biomarkers in Adult Patients with Plaque Psoriasis or Psoriatic Arthritis
Last Updated: 04/23/2026
SUMMARY
- The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
- Available data from post hoc analyses of VOYAGE 1, VOYAGE 2, ECLIPSE, DISCOVER 1, and DISCOVER 2 phase 3 clinical trials in adult patients with moderate to severe plaque psoriasis (PsO) and psoriatic arthritis (PsA) evaluating the impact of TREMFYA on inflammatory biomarkers associated with an increased risk of cardiovascular (CV) events are summarized below.1
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clinical DATA
Phase 3 Studies
Kearney et al (2025)1 reported post hoc analyses results from 3 phase 3 studies
(VOYAGE 1, VOYAGE 2, and ECLIPSE) evaluating the impact of TREMFYA on the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in adult patients with moderate to severe plaque PsO.
Study Design/Methods
- VOYAGE 1, VOYAGE 2, and ECLIPSE included patients with moderate to severe plaque PsO.
- A total of 837 patients in VOYAGE 1 were randomized through week (w) 16 in a 2:1:2 ratio to receive TREMFYA 100 mg at w0, w4, and w12 (n=329); placebo (PBO) at w0, w4, and w12 (n=174); or adalimumab 80 mg at w0, 40 mg at w1, and every 2 weeks (Q2W) thereafter (n=334).
- A total of 992 patients in VOYAGE 2 were randomized through w16 in a 2:1:1 ratio to receive TREMFYA 100 mg at w0, w4, and w12 (n=496); PBO at w0, w4, and w12 (n=248); or adalimumab 80 mg at w0, 40 mg at w1 and Q2W thereafter (n=248).
- A total of 1048 patients in ECLIPSE were randomized through w12 in a 1:1 ratio to receive TREMFYA 100 mg at w0, w4, and w12 (n=534); or secukinumab 2 x 150 mg at w0, 1, 2, 3, 4, 8, and 12 (n=514).
- Inclusion criteria: Adult patients with plaque PsO who were candidates for systemic treatment or phototherapy with a Psoriasis Area and Severity Index (PASI) score ≥12, an Investigator’s Global Assessment (IGA) score ≥3, and a body surface area (BSA) involvement ≥10%.
- Patients in the post hoc analysis had a full blood count test at baseline, and at w12 or w16. The associations between baseline NLR, PLR, and MLR and baseline PASI and C- reactive protein (CRP) levels were evaluated, along with the associations of these biomarkers with PASI at weeks 12 or 16 depending on the clinical trial.
Results
- In the VOYAGE 1 and VOYAGE 2 trials, TREMFYA treatment led to greater reductions in mean NLR, PLR, and MLR at w16 compared with PBO.
- In the ECLIPSE trial, no differences in mean NLR, PLR, and MLR were observed at w12 between patients treated with TREMFYA and those receiving secukinumab. See Table: Changes in NLR, PLR, and MLR from Baseline over Time.
| TREMFYA | P-Value | ||
|---|---|---|---|
| Baseline Mean (SD) | W16 or W12 Mean (SD) | Change from Baseline Mean (SD) | |
| Mean NLR and change from baseline to w16 (VOYAGE 1) | |||
| 2.68 (1.21) (n=326) | 2.42 (1.04) (n=320) | -0.28 (1.10) (n=320) | Nominal P=0.011a |
| Mean NLR and change from baseline to w16 (VOYAGE 2) | |||
| 2.73 (1.30) (n=483) | 2.25 (0.86) (n=480) | -0.47 (1.10) (n=480) | Nominal P=0.003a |
| Mean NLR and change from baseline to w12 (ECLIPSE) | |||
| 2.80 (1.35) (n=527) | 2.45 (1.15) (n=520) | -0.34 (1.23) (n=520) | - |
| Mean PLR and change from baseline to w16 (VOYAGE 1) | |||
| 151.7 (56.30) (n=325) | 135.8 (48.86) (n=318) | -15.6 (41.33) (n=318) | Nominal P=0.015a |
| Mean PLR and change from baseline to w16 (VOYAGE 2) | |||
| 152.80 (56.92) (n=478) | 131.90 (44.49) (n=476) | -20.9 (37.48)(n=478) | Nominal P=0.006a |
| Mean PLR and change from baseline to w12 (ECLIPSE) | |||
| 146.00 (55.20) (n=523) | 135.20 (48.98) (n=519) | -10.7 (38.84) (n=519) | - |
| Mean MLR and change from baseline to w16 (VOYAGE 1) | |||
| 0.243 (0.104) (n=326) | 0.234 (0.102) (n=320) | -0.010 (0.098) (n=320) | Nominal P=0.004a |
| Mean MLR and change from baseline to w16 (VOYAGE 2) | |||
| 0.257 (0.107) (n=483) | 0.224 (0.087) (n=480) | -0.034 (0.098) (n=479) | Nominal P=0.001a |
| Mean MLR and change from baseline to w12 (ECLIPSE) | |||
| 0.258 (0.115) (n=527) | 0.241 (0.104) (n=520) | -0.017 (0.091) (n=520) | Nominal P=0.498b |
| Abbreviations: MLR, monocyte/lymphocyte ratio; NLR, neutrophil/lymphocyte ratio; PBO, placebo; PLR, platelet/lymphocyte ratio; SD, standard deviation; w, week. aNominal P-value for TREMFYA vs PBO at week 16. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established. bNominal P-value for TREMFYA vs secukinumab at week 12. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established. | |||
- The association between baseline NLR, PLR, and MLR with PASI scores and CRP levels are presented in Table: Correlation of Baseline NLR, PLR, and MLR with Baseline PASI and CRP.
- There was a weak correlation between the three biomarkers with PASI at baseline and a modest correlation with CRP levels.
- No differences were observed in baseline NLR, PLR, and MLR levels between PASI 90 responders and nonresponders.
| NLR (Pearson’s r) | PLR (Pearson’s r) | MLR (Pearson’s r) | ||||
|---|---|---|---|---|---|---|
| PASI | CRP | PASI | CRP | PASI | CRP | |
| VOYAGE 1 | 0.146a | 0.307a | 0.116a | 0.215a | 0.043b | 0.181a |
| VOYAGE 2 | 0.178a | 0.248a | 0.123a | 0.234a | 0.155a | 0.229a |
| ECLIPSE | 0.129a | 0.226a | 0.083c | 0.122a | 0.117a | 0.155a |
| Abbreviations: CRP, C-reactive protein; MLR, monocyte/lymphocyte ratio; NLR, neutrophil/lymphocyte ratio; PASI, Psoriasis Area and Severity Index; PLR, platelet/lymphocyte ratio. Note: The endpoint was not controlled for multiple comparisons. Therefore, P-values are nominal, and statistical significance has not been established. aP=<0.001 bP=0.213 cP=0.008 | ||||||
DISCOVER 2
Merola et al (2024)2
Study Design/Methods
- DISCOVER 1 and DISCOVER 2 included patients with PsA who had a current diagnosis or a history of plaque 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
w0, 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 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 count (TJC) ≥3, swollen joint count (SJC) ≥3, and 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 included 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 an IGA score ≥3, PASI score ≥12, BSA ≥10%.
- Approximately 80% of patients from these 2 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 with 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).
aUsing MMRM adjusting for PsD type (PsO vs PsA); sex; prior biologic use; and NLR, presence of MetS, and medication use (csDMARDs, corticosteroids, NSAIDs) at BL. *P<0.05, **P<0.01, ***P<0.001 for GUS Q8W vs PBO. Included 34 (‡
Abbreviations: BL, baseline; csDMARD, conventional synthetic disease-modifying antirheumatic drug; GUS, guselkumab; LSM, least-squares mean; MetS, metabolic syndrome; MMRM, mixed model repeated measure; NLR, neutrophil-to-lymphocyte ratio; NSAID, nonsteroidal anti-inflammatory drug; PBO, placebo; PsA, psoriatic arthritis; PsD, psoriatic disease; PsO, psoriasis
- 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)3
, 8 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 CV 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 TJC ≥3, SJC ≥3, and CRP ≥0.3 mg/dL.
- Approximately 31% of patients previously received 1-2 tumor necrosis factor inhibitors (TNFi).
- Inclusion criteria (DISCOVER 2, N=739): patients were naïve to biologic agents and Janus kinase (JAK) inhibitors with TJC ≥5, SJC ≥5, CRP ≥0.6 mg/dL.
- Inclusion criteria (DISCOVER 1, N=381): patients with TJC ≥3, SJC ≥3, and CRP ≥0.3 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 were 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 in Psoriatic Arthritis (DAPSA) Low Disease Activity (LDA) score ≤14.
- 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.
- Psoraitic Arthritis Disease Activity score (PASDAS) LDA score ≤3.2.
- Minimal Disease Activity (MDA) achievement of ≥5 from 7 criteria.
- Mean/median values at baseline of hsCRP and NLR.
- High risk of CV events: hsCRP>10 mg/L4
and NLR >2.5.
- High risk of CV events: hsCRP>10 mg/L4
- The incidence of major adverse CV events (MACE): CV death, nonfatal myocardial infarction, or nonfatal stroke.
- Key endpoints at w24:
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.8
- Among patients with ≥1 CV risk factors, TREMFYA significantly reduced hsCRP and NLR levels compared with 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 Factors.
†
Abbreviations: BL, baseline; GUS, guselkumab; hsCRP, high-sensitivity C-reactive protein; LSM, least-squares mean; NLR, neutrophil-to-lymphocyte ratio; PBO, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks
Kavanaugh et al (2023)4 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 DMARDs, corticosteroids, and nonsteroidal 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.
Among the observed number of patients with available data at each visit. *P<0.05, **P<0.01, ***P<0.0001 for GUS Q4W/Q8W vs PBO. aAdjusted for BL NLR or hsCRP and BL use of csDMARDs, corticosteroids, and NSAIDs. bPercentage reductions were calculated based on the mean NLR values at BL and W100.
Abbreviations: BL, baseline; csDMARD, conventional synthetic disease-modifying antirheumatic drug; GUS, guselkumab; hsCRP, high-sensitivity C-reactive protein; LSM, least-squares mean; NLR, neutrophil-to-lymphocyte ratio; NSAID, nonsteroidal anti-inflammatory drug; PBO, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks
- TREMFYA showed significantly higher proportions of high CV-risk patients who achieved NLR ≤2.5 compared with PBO by w24 and maintained the rate through w100. See Figure: LSM Changes and Mean hsCRP Levels through W100.
Among the observed number of patients with available data at each visit. *P<0.01, **P<0.001, ***P<0.0001 for GUS Q4W/Q8W vs PBO. aAdjusted for BL NLR or hsCRP and BL use of csDMARDs, corticosteroids, and NSAIDs. bPercentage reductions were calculated based on the mean hsCRP levels at BL and w100.
Abbreviations: BL, baseline; csDMARD, conventional synthetic disease-modifying antirheumatic drug; GUS, guselkumab; hsCRP, high-sensitivity C-reactive protein; LSM, least-squares mean; NSAID, nonsteroidal anti-inflammatory drug; PBO, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks
Kirby et al (2023)5
Study Design/Methods
- Patients with moderate to severe PsO who had an IGA score ≥3, PASI score ≥12, and BSA ≥10% for at least 6 months and were candidates for systemic therapy or phototherapy were eligible for the study.6
,7 - 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 NLR 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®
References
| 1 | Kearney N, Gorecki P, Acciarri L, et al. Treatment of plaque psoriasis with guselkumab reduces systemic inflammatory burden as measured by neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and monocyte/lymphocyte ratio: a post hoc analysis of three randomised clinical trials. Dermatology. 2025;241(3):272-286. |
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