The effect of guselkumab on inhibiting radiographic progression in patients with active psoriatic arthritis: study protocol for APEX, a Phase 3b, multicenter, randomized, double-blind, placebo-controlled trial

Trials. 2023 Jan 10;24(1):22. doi: 10.1186/s13063-022-06945-y.

Abstract

Background: Guselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression.

Methods: Patients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively.

Discussion: DISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression.

Trial registration: This trial was registered at ClinicalTrials.gov, NCT04882098 . Registered on 11 May 2021.

Keywords: Psoriatic arthritis; Radiographic data; Randomized controlled trial; Spondyloarthritis.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antirheumatic Agents* / adverse effects
  • Arthritis, Psoriatic* / diagnostic imaging
  • Arthritis, Psoriatic* / drug therapy
  • Clinical Trials, Phase III as Topic
  • Double-Blind Method
  • Humans
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • guselkumab
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal
  • Antirheumatic Agents

Associated data

  • ClinicalTrials.gov/NCT04882098