Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• The effect of TREMFYA on radiographic progression in adult patients with active psoriatic arthritis (PsA) was evaluated in a randomized, double-blind, placebo-controlled, multicenter, phase 3 study (DISCOVER-2).^1-6
  • In the first and second reading sessions, the least squares (LS) mean change from baseline at week 24 in the PsA-modified van der Heijde-Sharp (vdH-S) score in the TREMFYA 100 mg every 4 weeks (q4w) group vs the placebo group was 0.29 vs 0.95 (P=0.011), and in the TREMFYA 100 mg every 8 weeks (q8w) group vs the placebo group was 0.52 vs 0.95 (P=0.072).
  • The LS mean change from baseline at week 52 in the PsA-modified vdH-S score in the TREMFYA 100 mg q4w and q8w groups was 1.10 and 1.13, respectively.
  • The mean change from baseline at week 100 in the PsA-modified vdH-S score in the TREMFYA 100 mg q4w and q8w groups was 1.68 and 1.50, respectively.
  • In the third reading session, the mean change from baseline in the total PsAmodified vdH-S score in the TREMFYA 100 mg q4w and q8w groups from weeks 52 to 100 was 0.8 and 0.5, respectively.⁶ 
• 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 24 in this ongoing study.^7-9 
  • At week 24, for the major secondary endpoint of LS mean change from baseline in total PsA-modified 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).^7,8

CLINICAL DATA

Phase 3 Study – DISCOVER-2

Mease et al (2020)^1,10, McInnes et al (2020)², McInnes et al (2021)³, Mease et al (2024)^4,11, Mease et al (2024)⁵, and Gottlieb et al (2023)^6,12 evaluated the effect of TREMFYA on radiographic progression using the PsAmodified vdH-S score in biologic-naïve adult patients with active PsA who had inadequate response to or intolerance of standard therapies (nonbiologic disease-modifying antirheumatic drugs [DMARDs], apremilast, and nonsteroidal anti-inflammatory drugs [NSAIDs]) in a randomized, doubleblind, placebo-controlled, multicenter, phase 3 study (DISCOVER-2).

Study Design/Methods

• The study design is presented in Figure: DISCOVER-2 Study Design.

• The primary endpoint was the proportion of patients achieving ≥20% improvement in the American College of Rheumatology criteria (ACR20) at week 24.
• Secondary endpoints adjusted for multiplicity included change from baseline in PsAmodified vdH-S score at week 24.
• Radiographs of the hands (posteroanterior) and feet (anteroposterior) were obtained at weeks 0 and 24 for the first reading session and at weeks 0, 24, and 52 for the second reading session and were evaluated independently by 2 central readers (masked to the order of radiographs and clinical data) using the PsA-modified vdH-S score. A third reader was used for adjudication and was blinded to treatment group and time point.
  • The total PsA-modified vdH-S score (range, 0-528) included addition of the following scores:
    • Joint erosion score (range 0-320; 0 for no erosions to 5 for extensive loss of bone from >50% of the articulating bone)
    • Joint space narrowing (JSN) score (range 0-208; 0 for no joint space narrowing to 4 for complete loss of joint space, bony ankylosis, or complete luxation)
  • The average of the joint erosion and the JSN scores were used in the analysis.
• For radiographic data, treatment failure rules, including discontinued study treatment, terminated study participation, initiated or increased DMARD or oral corticosteroid doses, or initiated protocol-prohibited PsA treatment, were not applied, and missing data were assumed to be missing at random and were imputed using multiple imputations.

Results

Patient Characteristics

• A total of 739 patients were randomized to receive TREMFYA 100 mg q8w (n=248), TREMFYA 100 mg q4w (n=245), or placebo (n=246). Of the randomized patients, 93% and 88% completed 1 year and 100 weeks of treatment, respectively.
• Baseline demographics were generally similar between the treatment groups and are summarized in Table: Baseline Demographic and Disease Characteristics.
• The majority of patients in the overall population (n=713; 96%), including those who received TREMFYA 100 mg q8w (n=234/248; 94%), TREMFYA 100 mg q4w (n=241/245; 98%), or placebo (n=238/246; 97%), had a PsA-modified vdH-S score >0.

Efficacy in Radiographic Reading

• A significantly greater proportion of patients achieved ACR20 at week 24 in the TREMFYA 100 mg q4w (64%) and q8w (64%) groups vs the placebo (33%) group (P<0.0001 for both TREMFYA groups).
• At week 24, significantly less progression of structural damage, as reflected by smaller changes from baseline in the PsA-modified vdH-S score, was observed in the TREMFYA 100 mg q4w group vs the placebo group (LS mean [95% confidence interval (CI)], 0.29 [0.05 to 0.63] vs 0.95 [0.61 to 1.29]; P=0.011), whereas a nonsignificant decrease in radiographic progression was observed in the TREMFYA 100 mg q8w group vs the placebo group (LS mean [95% CI], 0.52 [0.18 to 0.86] vs 0.95 [0.61 to 1.29]; P=0.072).
• At week 52, the estimated LS mean changes in the TREMFYA 100 mg q4w and q8w groups, respectively, were 1.10 (95% CI, 0.48-1.71) and 1.13 (95% CI, 0.52-1.73), and the LS mean differences compared with placebo were -1.06 (95% CI, -1.89 to -0.23) and -1.03 (95% CI, -1.85 to -0.20).
• At week 100, low rates of radiographic progression were observed across both the TREMFYA 100 mg q4w (1.68) and q8w (1.50) groups. Overall, mean changes in the total PsA-modified vdH-S score showed less radiographic progression from weeks 52 to 100 compared with weeks 0-52 in the 3 groups.
• For the third reading session, patients continuing study treatment at week 52 underwent assessments at weeks 0, 24, 52, and 100 (or at discontinuation after week 52). Readers were blinded to the treatment group and time point.⁶ 
  • Mean changes in the total PsA-modified vdH-S score, JSN, and erosion scores were reported.
  • Among patients who did and did not achieve clinical response at week 100, changes in the total vdH-S scores from weeks 0-100 were determined by ≥20%/≥50%/≥70% improvement in the American College of Rheumatology criteria (ACR20/50/70), low disease activity (LDA) based on Disease Activity in PsA (DAPSA) score (≤14) or PsA Disease Activity Score (PASDAS; ≤3.2), minimal disease activity (MDA), and normalized Health Assessment Questionnaire-Disability Index (HAQ-DI) score (<0.5).
• From weeks 0-24, the mean changes in radiographic scores indicated that the rates of radiographic progression of joint damage were numerically lower in TREMFYA-treated vs placebo-treated patient.
• For mean changes in radiographic scores, see Table: Change in PsA-Modifed vdH-S Score Through Weeks 24, 52, and 100.

• For association between radiographic changes and measures of clinical outcomes, see Table: Changes in PsA-Modified Total vdH-S Score from Baseline Through Week 100 by Clinical Responses at Week 52 and Week 100.

• For clinical response in patients with or without radiographic progression, see Table: Proportions of Patients Achieving MDA Components at Week 24, 52, and 100 by Treatment Groups and Progression Status.

Correlation of Baseline PsA-Modified vdH-S Scores With Baseline PsA Parameters

• For correlation between baseline PsA parameters with PsA-modified vdH-S Score among patients randomized to receive TREMFYA q4w or q8w (n=449), see Table: Correlation Between Baseline PsA-Modified vdH-S Score and Radiographic Progression Risk Factors.

Impact on Total PsA-Modified vdH-S Scores Through Week 100

• The impact on the total PsA-modified vdH-S scores among patients randomized to receive TREMFYA (n=440) is presented in Table: Multivariate Associations of DAPSA Endpoints at Week 8 and Baseline Risk Factors of Radiographic Progression Through Week 100.

• For data on the impact of achieving DAPSA endpoints at week 8 on time-averaged LS mean changes from baseline to week 52 and 100, see Table: Time-Averaged LS Mean Change in Total PSA-Modified vdH-S Score by DAPSA Endpoints.

• The data on effect of clinical Disease Activity Index for psoriatic arthritis (cDAPSA) LDA/remission (REM) are presented in Table: LS Mean Change in Total PSA-Modified vdH-S Score by cDAPSA LDA/REM at Week 52 and Week 100

Safety

• Safety results summarized below are from patients enrolled in DISCOVER-2 and are not limited to patients with radiographic progression.
• The safety results through week 24 are presented in Table: Summary of Safety Results Through Week 24.

• From week 24 through week 52, the rate of serious infection did not increase in patients treated with TREMFYA and no additional malignancies or major cardiovascular events were reported after week 24.²
• Through week 112³:
  • Death was reported in 1 patient from the placebo to TREMFYA q4w crossover group due to road traffic accident.
  • Opportunistic infections, including fungal esophagitis and disseminated herpes zoster, were reported in 2 patients in the TREMFYA q8w group, and listeria meningitis was reported in 1 patient from the placebo to TREMFYA q4w crossover group.
  • Patients treated with TREMFYA did not report any inflammatory bowel disease.
  • Patients did not report any anaphylactic or serum sickness reactions or active tuberculosis.

Phase 3b Study – APEX

Mease et al (2025)^7,8 reported the clinical, radiographic, and safety outcomes of TREMFYA compared with placebo in biologic-naïve patients with active PsA and known risk factors for radiographic progression in an ongoing phase 3b, randomized, double-blind, placebo-controlled study.

Study Design/Methods

• Select inclusion criteria:^9,13
  • Age ≥18 years old
  • 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
• Select exclusion criteria:
  • Previous biologic or Janus kinase inhibitor therapy
  • Currently receiving ≥3 csDMARDs
• The study design is summarized in Figure: APEX Study Design.

• Multiplicity-controlled endpoints:^7,8   
  • Primary endpoint: ACR20 response at week 24
  • Major secondary endpoint: mean change from baseline in total PsA-modified vdH-S score at week 24
• Non-controlled endpoints:
  • Proportion of patients achieving ACR50 and ACR70 responses at week 24
  • Other endpoints at week 24 included LS mean changes from baseline in erosion score and JSN score, the proportions of patients with a change in PsA-modified vdH-S score of ≤0.5 and ≤0, the proportion of patients achieving Investigator’s Global Assessment (IGA) 0/1 response, the proportion of patients achieving ≥90% improvement from baseline in Psoriasis Area Severity Index (PASI 90) score, and LS mean change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI).
• 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 week 24.
• Statistical methods:⁹ 
  • Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively.
  • Statistical testing will be performed using 2-sided tests. Overall type I error of the hypotheses will be controlled at a significance level of ≤0.05 and will be tested in a fixed sequence.

Results

Patient Characteristics

• A total of 1054 patients were enrolled and randomized.⁷
  • The mFAS included 1020 patients.
  • The safety analysis set included all 1054 patients randomized.
• Select baseline characteristics are summarized in Table: Select Baseline Characteristics.

Efficacy: Radiographic Progression Endpoints

• The results for radiographic progression endpoints at week 24 are summarized in the Table: Summary of Radiographic Progression Endpoints at Week 24 in the Completed mFAS

Safety

• The results for the safety profile through week 24 are summarized in Table: Summary of Safety Profile Through Week 24.

• The most common AEs were respiratory infections, headache, diarrhea, and psoriatic arthropathy.⁸ 

LITERATURE SEARCH

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