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TREMFYA® (guselkumab)
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TREMFYA - Overview of the APEX Clinical Trial
Last Updated: 12/17/2025
SUMMARY
- The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
- APEX was designed to evaluate the clinical, radiographic, and safety outcomes of TREMFYA in a phase 3b, randomized, double-blind, placebo-controlled study in biologic-naïve patients with active psoriatic arthritis (PsA) and known risk factors for radiographic progression. Results are available through week (W) 48 in this ongoing study.1
- 5 - The primary endpoint was the proportion of the patients who achieved ≥20% improvement from baseline in the American College of Rheumatology Criteria (ACR20) at W24. Results were significantly greater in both TREMFYA groups compared to placebo (PBO) (ACR20: TREMFYA every 4 weeks [q4w], 66.6% and TREMFYA every 8 weeks [q8w], 68.3% vs placebo, 47.0%; P<0.001 and P<0.001, respectively).1-3
- At W24, for the major secondary endpoint of least square (LS) mean change from baseline in total PsA-modified van der Heijde-Sharp (vdH-S) score, patients in both TREMFYA groups exhibited significantly less radiographic progression compared to those in the placebo group (LS mean changes in PsA-modified vdH-S score: TREMFYA q4w, 0.55 and TREMFYA q8w, 0.54, vs placebo, 1.35; P=0.002 and P<0.001, respectively).1-3
- At W48, the ACR20 response was 71% in patients receiving TREMFYA q4w, 74% in patients receiving TREMFYA q8w, and 71% in the placebo crossover to TREMFYA q4w group.4
- From W24 to W48, the LS mean change in PsA-modified vdH-S score was 0.24 in patients receiving TREMFYA q4w, 0.32 in patients receiving TREMFYA q8w, and 0.41 in the placebo crossover to TREMFYA q4w group.4
- Through W48, adverse events (AEs), serious adverse events (SAEs), infection rates, and serious infection rates were reported as follows:4
- AEs occurred in 51% (142/280) and 55% (214/388) of patients in the TREMFYA q4w and q8w groups, respectively vs 34% (127/372) in the placebo crossover to TREMFYA q4w group.
- SAEs occurred in 4% (10/280) and 5% (21/388) of patients in the TREMFYA q4w and q8w groups, respectively vs 4% (16/372) in the placebo crossover to TREMFYA q4w group.
- Infection rates were reported at 30% (84/280) and 34% (131/388) of patients in the TREMFYA q4w and q8w groups, respectively vs 13% (50/372) in the placebo crossover to TREMFYA q4w group.
- Serious infection rates were reported at 1% (2/280) and 2% (6/388) of patients in the TREMFYA q4w and q8w groups, respectively vs 1% (4/372) in the placebo crossover to TREMFYA q4w group.
CLINICAL STUDY
Mease et al (2025)1-3 and Ritchlin et al (2025)4 reported efficacy and safety outcomes of TREMFYA compared with placebo in biologic-naïve adult patients with active PsA and known risk factors for radiographic progression in an ongoing phase 3b, randomized, double-blind, placebo-controlled study. Results are available through W48 in this ongoing study.
- Selected inclusion criteria:1-3,
5,6 - Adults (≥18 years old) with a diagnosis of PsA for ≥6 months and met ClASsification criteria for Psoriatic ARthritis (CASPAR) at screening
- Active PsA (despite previous conventional synthetic disease-modifying antirheumatic drugs [csDMARD], apremilast, and/or nonsteroidal anti-inflammatory drug [NSAID] therapy): ≥3 swollen/tender joints and CRP ≥0.3 mg/dL
- ≥2 joints with erosions on baseline radiographs of the hands and feet
- Active plaque psoriasis (PsO), with ≥1 psoriatic plaque of ≥2 cm diameter and/or nail changes consistent with PsO
- Selected exclusion criteria:
- Previous biologic or Janus kinase inhibitor therapy
- Received the following therapies within the specified timeframe before the first study agent administration:
- Any treatment that could confound PsO evaluation: topical (2 weeks), systemic (4 weeks), or phototherapy (4 weeks)
- Systemic immunosuppressants (4 weeks)
- csDMARDs (other than methotrexate [MTX], sulfasalazine, hydroxychloroquine, or leflunomide; 4 weeks)
- Experimental antibody or biological therapy (6 months)
- Intramuscular or intravenous corticosteroids (4 weeks)
- Lithium (4 weeks)
- Patients were allowed to receive concomitant stable NSAIDs, oral corticosteroids (prednisone ≤10 mg/d or equivalent), and select csDMARDs (MTX ≤25 mg/wk, sulfasalazine ≤3 g/d, hydroxychloroquine ≤400 mg/d, or leflunomide ≤20 mg/d). Patients could not receive >2 concomitant csDMARDs or MTX with leflunomide through W24.
- The study design is summarized in Figure: APEX Study Design.
Abbreviations: EE, early escape; F/U, follow-up; GUS, guselkumab; LTE, long-term extension; Q4W, every 4 weeks; Q8W, every 8 weeks; PBO, placebo; PE, primary endpoint; R, randomization; SC, subcutaneous; vs, versus; W, week.
a
b
c
d
- Multiplicity-controlled endpoints:1-3,5,6
- Primary endpoint: ACR20 response at W24
- Major secondary endpoint: LS mean change from baseline in total PsA-modified
vdH-S score at W24
- Selected other endpoints at W24 or W48:
- Proportion of patients achieving ACR20 at W48, ACR50/70 at W24, ACR50/70 at W48
- LS mean change in total PsA-modified vdH-S score at W24→W48
- LS mean changes in erosion score and joint space narrowing (JSN) score from W0→W24 and from W24→W48
- Proportions of patients with no radiographic progression: change from baseline in PsA-modified vdH-S score of ≤0 at W24 and W48
- Among patients with ≥3% psoriatic body surface area (BSA) and Investigator’s Global Assessment (IGA) ≥2 at baseline: the response rates for patients achieving ≥90% improvement from baseline in Psoriasis Area Severity Index scores (PASI 90) and IGA 0/1 response at W24 and W48
- LS mean percent change in modified Nail Psoriasis Severity Index (among patients with mNAPSI>0 at baseline) from W0→W24 and from W24→W48
- LS mean change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from W0→W24 and from W24→W48
- The modified full analysis set (mFAS) was defined as all randomized patients excluding those from Ukraine sites rendered unable to support key study operations due to major disruptions (main efficacy analysis set).
- Safety analyses included all patients who received ≥1 dose of study treatment through W48.
Results
Patient Characteristics
- A total of 1054 patients were enrolled and randomized.1-3
- The mFAS included 1020 patients (TREMFYA q4w, n=273; TREMFYA q8w, n=371; PBO, n=376).
- The safety analysis set included all 1054 patients randomized.
- Selected baseline characteristic are summarized in Table: Selected Baseline Characteristics.
| Parameters | TREMFYA 100 mg q4w (n=273) | TREMFYA 100 mg q8w (n=371) | PBO (n=376) |
|---|---|---|---|
| Baseline Demographics | |||
| Age, years | 52.2 (13.2) | 53.2 (12.9) | 53.5 (13.0) |
| Male,c n (%) | 149 (54.6) | 199 (53.6) | 213 (56.6) |
| BMI, kg/m2 | 29.4 (6.0) | 29.0 (5.6) | 28.9 (5.7) |
| PsA Characteristics | |||
| PsA disease duration, years | 7.5 (7.1) | 7.2 (7.6) | 7.2 (6.9) |
| SJC (0-66) | 11.6 (9.4) | 12.1 (8.5) | 11.8 (8.9) |
| TJC (0-68) | 21.2 (14.6) | 20.6 (13.4) | 20.5 (13.9) |
| HAQ-DI (0-3) | 1.2 (0.7) | 1.2 (0.6) | 1.2 (0.7) |
| CRP (mg/dL) | 1.7 (2.9) | 1.5 (2.0) | 1.7 (2.5) |
| Enthesitis/Dactylitis, % | 57.9/43.9 | 58.6/39.3 | 58.6/44.9 |
| PsO Characteristics | |||
| % BSA | 15.0 (19.2) | 16.5 (21.9) | 16.3 (21.5) |
| PASI (0-72) | 7.6 (8.3) | 8.3 (10.1) | 8.2 (9.5) |
| Radiographic Characteristics | |||
| PsA-modified vdH-s score (0-528) | 27.7 (47.6) | 26.7 (43.4) | 26.8 (42.2) |
| Erosion score (0-320) | 13.7 (24.3) | 13.4 (21.9) | 13.4 (20.7) |
| JSN score (0-208) | 14.0 (24.2) | 13.3 (22.8) | 13.4 (22.4) |
| Abbreviations: BMI, body mass index; BSA, body surface area; CRP, C-reactive protein; DSS, dactylitis severity score; HAQ-DI, health assessment questionnaire-disability index; IQR, interquartile range; JSN, joint space narrowing; LEI, Leeds enthesitis index; PASI, psoriasis area and severity index; PBO, placebo; PsA, psoriatic arthritis; PsO, psoriasis; q4W, every 4 weeks; q8W, every 8 weeks; SD, standard deviation; SJC, swollen joint count; TJC, tender joint count; vdH-S, van der Heijde-Sharp. aValues are reported as mean (SD), n (%) unless otherwise noted. bBaseline characteristics are reported for the modified full analysis set, excluding 34 participants who were enrolled at 5 sites in Ukraine that could not carry out key study operations. cParticipant sex was reported by the investigators by selecting one of the following options: female, male, unknown, or undifferentiated. | |||
Efficacy
Week 24 Efficacy Results
- Results for the primary, major secondary, and selected other endpoints at W24 are summarized in the following tables:1-3
| Endpoints | TREMFYA 100 mg q4w (n=273) | TREMFYA 100 mg q8w (n=371) | PBO (n=376) |
|---|---|---|---|
| Primary endpointa,c | |||
| ACR20 response at W24, % | 66.6 | 68.3 | 47.0 |
| Treatment difference vs PBO (95% CI) | 19.7 (12.1, 27.2) | 21.3 (14.4, 28.2) | - |
| P-value | <0.001 | <0.001 | - |
| Major secondary endpointb,c,e | |||
| LS mean change in total PsA-modified vdH-S score W0→W24 | 0.55 | 0.54 | 1.35 |
| Treatment difference vs PBO (95% CI) | -0.80 (-1.31, -0.28) | -0.80 (-1.28, -0.33) | - |
| P-value | 0.002 | <0.001 | - |
| Selected other endpointsc | |||
| ACR50 response at W24, % | 41.4 | 42.2 | 20.5 |
| Nominal P-value | <0.001d | <0.001d | - |
| ACR70 response at W24, % | 22.0 | 22.4 | 11.2 |
| Nominal P-value | <0.001d | <0.001d | - |
| LS mean change in ES from W0→W24f,g | 0.35 | 0.32 | 0.87 |
| Nominal P-value | 0.002d | <0.001d | - |
| LS mean change JSN scoreg,h | 0.22 | 0.24 | 0.50 |
| Nominal P-value | 0.025d | 0.027d | - |
| Change from baseline in PsA-modified vdH-S score ≤0, % | 67.3 | 62.8 | 53.0 |
| Nominal P-value | <0.001d | 0.007d | - |
| LS mean change in HAQ-DI from W0→W24fc,i,j,k | -0.41 (n=271) | -0.42 (n=365) | -0.27 (n=372) |
| Nominal P-value | <0.001d | <0.001d | - |
| Abbreviations: ACR, American College of Rheumatology; ANOCOVA; analysis of covariance; BSA, body surface area; CI, confidence interval; CMH, Cochran-Mantel-Haenszel; ES, erosion score; HAQ-DI, health assessment questionnaire-disability index; JSN, joint space narrowing; LS, least square; mFAS, modified full analysis set; MI, multiple imputation; MMRM, mixed-effect model for repeated measures; ND/MD, natural disaster/ major disruption; PBO, placebo; PsA, psoriatic arthritis; q4W, every 4 weeks; q8W, every 8 weeks; vdH-S, van der Heijde-Sharp; W, week. aTheprimary endpoint P-value is multiplicity controlled using a fixed sequence testing procedure and can be used to determine statistical significance. Statistics are based on CMH across multiply imputed datasets. bThe major secondary endpoint P-value is multiplicity controlled using a fixed sequence testing procedure and can be used to determine statistical significance. Statistics are based on analysis of covariance across multiply imputed datasets. cEfficacy analyses are from the mFAS, which included all randomized patients excluding those from Ukraine sites rendered unable to support key study operations due to major disruptions. dThese endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established. e f g h i j k | |||
| Endpoints | TREMFYA 100 mg q4w (n=159) | TREMFYA 100 mg q8w (n=231) | PBO (n=223) |
|---|---|---|---|
| PASI 90 response, %a-d | 69.4 | 60.0 | 22.0 |
| Nominal P-value | <0.001e | <0.001e | - |
| IGA 0/1 response, %a,b,c,f,g | 72.8 | 67.9 | 31.3 |
| Nominal P-value | <0.001e | <0.001e | - |
| mNAPSI, LS mean % change from baselinea,b,c,h | -43.0 (n=163) | -35.8 (n=227) | 16.1 (n=257) |
| Nominal P-value | <0.01e | <0.01e | - |
| Abbreviations: CI, confidence interval; DMARD, disease-modifying antirheumatic drug; GLMM, generalized linear mixed model; IGA, Investigator’s Global Assessment; LS, least square; mFAS, modified full analysis set; MMRM, mixed-effect model for repeated measures; mNAPSI, modified Nail Psoriasis Severity Index; ND/MD, natural disaster/ major disruption; NRI, non-responder imputation; PASI, psoriasis area and severity index; PBO, placebo; PsA, psoriatic arthritis; q4W, every 4 weeks; q8W, every 8 weeks; W, week. aEfficacy analyses are from the mFAS, which included all randomized patients excluding those from Ukraine sites rendered unable to support key study operations due to major disruptions. bBased on Generalized Linear Mixed Models. cAmong patients who had ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline. PASI 90 response: ≥90% improvement from baseline in PASI score. dResponse rates based on GLMMs adjusted for treatment group, visit, treatment group x visit, and randomization stratification level. Through W24, patients who initiated/increased dose of oral corticosteroid or non-biologic DMARD or initiated protocol prohibited therapies for PsA were also considered nonresponders. Other missing data were imputed using NRI. eThese endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established. fIGA 0/1 response is defined as an IGA score of 0 (cleared) or 1 (minimal) and ≥2 grade improvement from baseline. gAfter application of treatment failure rules, data from participants with study agent discontinuation/severe noncompliance due to ND/MD were not used. Any other missing data were imputed by NRI; response rates were determined using a GLMM. hAfter application of treatment failure rules, data from participants with study agent discontinuation/severe noncompliance due to ND/MD were not used. Other missing data were not imputed; LS mean changes were determined using MMRM. | |||
- The results for other endpoints at W48 are summarized in the table: Summary of Selected Other Endpoints at W484,7
| Endpoints | TREMFYA 100 mg q4w (n=273) | TREMFYA 100 mg q8w (n=371) | PBO crossover to TREMFYA q4w (n=376) |
|---|---|---|---|
| ACR20 response, %b-d | 71 | 74 | 71 |
| ACR50 response, %b-d | 51 | 56 | 48 |
| ACR70 response, %b-d | 31 | 35 | 26 |
| LS mean change in total PsA-modified vdH-S scoreW24→W48b,e,f,g,h | 0.24 | 0.32 | 0.41 |
| LS mean change in erosion score W24→W48b,e,h,i,j | 0.09 | 0.12 | 0.16 |
| LS mean change in JSN score W24→W48b,e,h,i,j | 0.15 | 0.21 | 0.25 |
| Change from baseline in PsA-Modified vdH-S score ≤0 at W48, %b,c,e,m | 69.1 | 65.7 | 60.1 |
| PASI 90 response, %b,k,l | 80 (n=159) | 74 (n=231) | 71 (n=223) |
| IGA 0/1 response, %b,l,o,n,p,q | 73 | 77 | 79 |
| LS mean % change in mNAPSI W24→W48b,r,s,t | -60.6 | -65.0 | -63.1 |
| LS mean change in HAQ-DI W24→W48b,r,s,u | -0.49 (n=271) | -0.52 (n=366) | -0.49 (n=372) |
| Abbreviations: ACR, American College of Rheumatology; ANCOVA, Analysis of Covariance; BSA, body surface area; CI, confidence interval; CMI, clinical meaning improvement; GLMM, generalized linear mixed model; HAQ-DI, health assessment questionnaire-disability indexICE, intercurrent event; IGA, Investigator’s Global Assessment; JSN, joint space narrow; LS, least square; mFAS, modified full analysis set; MI, multiple imputation; MMRM, mixed-effect model for repeated measures; ND/MD, natural disaster or major disruption; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; PBO, placebo; PsA, psoriatic arthritis; q4W, every 4 weeks; q8W, every 8 weeks; vdH-S, van der Heijde-Sharp; W, week. aNo statistical testing was conducted after W24 in the APEX trial. bEfficacy analyses are from the mFAS, which included all randomized patients excluding those from Ukraine sites rendered unable to support key study operations due to major disruptions. cShown are the average proportion of mFAS pts with ACR20/50/70 responses, over the 200 MI datasets. dThrough w48, patients who discontinued study intervention for any reason except ND/MD were treated as nonresponders. Through w24, pts who initiated/increased dose of oral corticosteroid or non-biologic DMARD or initiated protocol prohibited therapies for PsA were treated as nonresponders; after W24, these pts were not treated as nonresponders; after W24, these pts were not treated as nonresponders. Data from pts who discontinued study intervention or with severe treatment noncompliance due to ND/MD were imputed using MI at all subsequent timepoints or at the next timepoint, respectively. Other missing data were imputed using NRI. eReading sessions 1 and 2 were prespecified in the protocol. Session 1 included independent assessment of images by two blinded central readers and a blinded adjudicator from W0–W24. Session 2 included re-reading of images by two blinded central readers and a blinded adjudicator from W24–W48. The same readers were used for reading sessions 1 and 2. fFor patients with missing W48 radiographs, W0/24 radiographs were not re-read during reading session 2; W0/24 data from reading session 1 was used if available. gScore change was assessed in the mFAS according to the Adjusted Treatment Policy Estimand: irrespective of background PsA medication or adherence to study intervention; in situations when ND/MD occurred, observed data collected after ND/MD was not used; data for visits after ND/MD and missing data were imputed using full conditional specifications multiple imputation. hLS mean change and CIs based on combining ANCOVA model (explanatory variables: baseline modified vdH-S score, treatment group, and randomization stratification level) results from each multiple imputation dataset. iMissing Data Imputation: After applying the ICE strategies, the remaining missing data were imputed using MI. The corresponding n includes all subjects with change data at W48 after applying the ICE strategies and Missing Data Imputation. jAnalysis Model: after applying the ICE Strategy and Missing Data Imputation, data at W48 was analyzed using an ANCOVA model for each MI dataset. The explanatory variables of the ANCOVA model included baseline modified vdH-S score, treatment group, and the randomization stratification level. kResponse rates based on GLMMs adjusted for treatment group, visit, treatment group x visit, and randomization stratification level. Through W48, patients who discontinued study intervention for any reason except ND/MD were treated as nonresponders. Through W24, patients who initiated/increased dose of oral corticosteroid or non-biologic DMARD or initiated protocol prohibited therapies for PsA were also considered nonresponders; after W24, these patients were not treated as nonresponders. Missing data from ND/MD was handled within the model. Other missing data were imputed using NRI. l m n o p q r s t u | |||
Safety
Week 24 Safety Results
- Safety results through W24 are summarized in Table: Summary of Safety Results Through W24.1,3
| TREMFYA 100 mg q4w (n=280) | TREMFYA 100 mg q8w (n=388) | PBO (n=386) | |
|---|---|---|---|
| Mean weeks of follow up | 24.0 | 23.9 | 23.8 |
| Patients with ≥1: | |||
| AE | 107 (38.2%) | 165 (42.5%) | 144 (37.3%) |
| SAE | 5 (1.8%) | 12 (3.1%) | 10 (2.6%) |
| AE leading to study agent d/c | 2 (0.7%) | 6 (1.5%) | 1 (0.3%) |
| Infection | 52 (18.6%) | 91 (23.5%) | 81 (21%) |
| Serious infection | 2 (0.7%) | 5 (1.3%) | 1 (0.3%) |
| Active tuberculosis | 0 | 0 | 0 |
| Opportunistic infection | 0 | 0 | 0 |
| Malignancya | 0 | 2 (0.5%) | 0 |
| Venous thromboembolism event | 1 (0.4%) | 1 (0.3%) | 1 (0.3%) |
| MACEb | 0 | 1 (0.3%) | 0 |
| Anaphylactic or serum sickness reaction | 0 | 0 | 0 |
| Clinically important hepatic disorderc | 0 | 0 | 0 |
| Injection-site reactionb | 8 (2.9%) | 2 (0.5%) | 10 (1.5%) |
| Abbreviations: AE, adverse event; d/c, discontinuation; MACE, major adverse cardiovascular event; PBO, placebo; q4W, every 4 weeks; q8W, every 8 weeks; SAE, serious adverse event; W, week. Note: Data are n (%) unless otherwise noted aTwo patients with malignancy were prostate cancer and renal cancer. bOne patient with MACE was myocardial infarction. cClinically important hepatic disorders were prespecified as AE terms within the Medical Dictionary for Regulatory Activities category of Drug-Related Hepatic Disorders that met the criteria for an SAE or led to study agent discontinuation. dInjection-site reactions were defined as any adverse reactions at a study intervention injection site. | |||
- One unvaccinated patient in the TREMFYA q4w group died due to COVID-19.
- No new onset for inflammatory bowel disease was reported.1,3,8
- The most common AEs (>5%) were upper respiratory infections (TREMFYA q4w, 15 cases [5.4%]; TREMFYA q8w, 20 cases [5.2%]; PBO, 22 cases [5.7%]) and COVID-19 (TREMFYA q4w, 9 cases [3.2%]; TREMFYA q8w, 22 cases [5.7%]; PBO, 21 cases [5.4%]).3
Week 48 Safety Results
- Safety results through W48 are summarized in Table: Summary of Safety Results Through W48.4
| TREMFYA 100 mg q4w W0→W48 (n=280) | TREMFYA 100 mg q8w W0→W48 (n=388) | PBO crossover to TREMFYA 100 mg q4w W24→W48a (n=372) | |
|---|---|---|---|
| Mean weeks of follow up | 47.3 | 46.9 | 23.5 |
| Patients with ≥1: | |||
| AE | 142 (51%) | 214 (55%) | 127 (34%) |
| SAE | 10 (4%) | 21 (5%) | 16 (4%) |
| AE leading to study agent d/c | 4 (1%) | 10 (3%) | 8 (2%) |
| Infection | 84 (30%) | 131 (34%) | 50 (13%) |
| Serious infection | 2 (1%) | 6 (2%) | 4 (1%) |
| Active tuberculosis | 0 | 0 | 0 |
| Opportunistic infection | 0 | 0 | 0 |
| Venous thromboembolism event | 1 (0.4) | 2 (0.5) | 0 |
| MACEb | 0 | 2 (0.5%) | 4 (1%) |
| Anaphylactic or serum sickness reaction | 0 | 0 | 0 |
| Clinically important hepatic disorder | 1 (0.4) | 0 | 0 |
| Abbreviations: AE, adverse event; d/c, discontinuation; PBO, placebo; q4W, every 4 weeks; q8W, every 8 weeks; SAE, serious adverse event; W, week. Note: Data are n (%) unless otherwise noted aFor subjects in the PBO group who received TREMFYA at Week 24 or another time point, only data on or after the first administration of GUS are included. Data prior to the first administration of TREMFYA are not included. bThis includes the case reported through Week 24. | |||
Literature Search
A literature search of MEDLINE®
References
| 1 | Mease PJ, Ritchlin CT, Coates LC, et al. Inhibition of structural damage progression with guselkumab, a selective IL-23i, in participants with active PsA: results through week 24 of the phase 3b, randomized, double-blind, placebo-controlled APEX study. Oral Presentation presented at: European Alliance of Association for Rheumatology (EULAR); June 11-14, 2025; Barcelona, Spain. |
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