SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• APEX (NCT04882098) is a phase 3b study designed to evaluate the efficacy and safety of TREMFYA in biologic-naïve patients with active psoriatic arthritis (PsA) and known risk factors for radiographic progression.^1,2 Results are not currently available.
• Details regarding the study status and study design of APEX can be found on clinicaltrials.gov and are summarized below.

CLINICAL STUDY

Phase 3b Study - APEX

Ritchlin et al (2022)¹ designed a phase 3b, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of TREMFYA compared with placebo in biologic-naïve patients with active PsA and known risk factors for radiographic progression (N=950). Results are not currently available.

Study Design/Methods

• Select inclusion criteria included patients ≥18 years old with active PsA despite previous treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), apremilast, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy; diagnosis of PsA for ≥6 months prior to first administration of the study medication and meeting ClASsification Criteria for Psoriatic ARthritis (CASPAR) at screening; active PsA (≥3 swollen and ≥3 tender joints and C-reactive protein [CRP] level ≥0.3 mg/dL); ≥2 joints with erosions on the baseline radiographs of the hands and feet; active plaque psoriasis (PsO) with ≥1 psoriatic plaque of ≥2 cm diameter and/or psoriatic nail changes; ≥1 of the following PsA subsets:
  • distal interphalangeal joint involvement
  • polyarticular arthritis with absence of rheumatoid nodules
  • arthritis mutilans²
  • asymmetric peripheral arthritis
  • spondylitis with peripheral arthritis
• Select exclusion criteria included, current use of ≥3 csDMARDs, previous use of biologic therapy or Janus kinase (JAK) inhibitors for PsA or PsO, prior use of systemic immunosuppressants or apremilast within 4 weeks of the first administration of the study medication, systemic lupus erythematosus, and presence of other inflammatory diseases (including rheumatoid arthritis, axial spondyloarthritis, non-radiographic axial spondyloarthritis, and Lyme disease).^1,2
• Findings from DISCOVER-2 informed the design of APEX. Sample sizes of 350, 250, and 350 for placebo, TREMFYA every 4 weeks, and TREMFYA every 8 weeks treatment groups, respectively, are expected to provide adequate power to detect a significant difference in van der Heijde-Sharp (vdH-S) score change at week 24; and a significant difference in the American College of Rheumatology (ACR) 20% improvement in response rates (ACR20) between each TREMFYA group and placebo at week 24.
• The study design is summarized in Figure: APEX Study Design.

• Primary endpoint:
  • Proportion of patients who achieve the ACR20 response at week 24
    • An improvement of ≥20% from baseline in swollen joint count (66 joints) and tender joint count (68 joints)
    • An improvement of ≥20% from baseline in 3 of the following assessments: patient’s assessment of pain (Visual Analog Scale [VAS]), Patient’s Global Assessment of Disease Activity (arthritis, VAS), Physician’s Global Assessment (PGA) of Disease Activity, Health Assessment Questionnaire Disability Index (HAQ-DI), serum CRP level
• Major secondary endpoint:
  • Mean change from baseline in PsA-modified vdH-S score at week 24
• Other secondary endpoints:
  • Safety through week 60 (through week 168 for patients who enter the long-term extension [LTE])
    • Frequency and type of adverse events (AEs), serious AEs, reasonably related AEs, AEs leading to discontinuation of treatment, infections, and injection-site reactions
    • Frequency of laboratory (chemistry, hematology) abnormalities and maximum toxicity grades based on the Common Terminology Criteria for Adverse Events (CTCAE 5.0)
  • Pharmacokinetics and immunogenicity through week 60 (through week 168 for patients who enter the LTE)
    • Serum guselkumab concentration
    • Incidence of antibodies to TREMFYA
  • Select other endpoints through week 156³:
    • Change from baseline through week 156 in the following:
      • ACR 50% improvement (ACR50) in response rate
      • ACR 70% improvement (ACR70) in response rate
      • HAQ-DI
      • Disease Activity Score 28 (DAS28; CRP)
      • Modified Psoriatic Arthritis Response Criteria (mPsARC)
      • Dactylitis
      • Enthesitis
      • Investigator’s Global Assessment (IGA)
      • Psoriasis Area and Severity Index (PASI)
      • Dermatology Life Quality Index (DLQI)
      • Modified Nail Psoriasis Severity Index (mNAPSI)
      • Work Productivity and Activity Impairment Questionnaire (WPAI)
      • Modified Composite Psoriatic Disease Activity Index (mCPDAI)
      • Psoriatic Arthritis Impact of Disease 12-item Questionnaire (PsAID12)
      • Disease Activity Index for Psoriatic Arthritis (DAPSA)
      • Minimal Disease Activity (MDA)
      • Very Low Disease Activity (VLDA)
      • Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
• Statistical methods:
  • 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.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 11 March 2024.