Guselkumab slows joint damage progression in PsA

In an analysis of the phase 3b APEX study, the IL-23p19- targeting antibody guselkumab significantly improved clinical outcomes in biologic-naïve participants with psoriatic arthritis (PsA) over 24 weeks. Moreover, it inhibited joint damage progression.

In active PsA, structural damage resulting from chronic inflammation leads to poorer outcomes [1]. The earlier DISCOVER-2 trial showed that guselkumab administered every 4 weeks (Q4W) but not every 8 weeks (Q8W) significantly reduced radiographic progression versus placebo in biologic- naïve participants [2]. “So, the goal of the phase 3b APEX study is to more closely evaluate the ability of both Q4W and Q8W dosing regimens to prevent structural progression,” explained Prof. Philip J. Mease (Swedish Medical Center, WA, USA) [3].

In the ongoing APEX trial (NCT04882098), 1,020 biologic- naïve adults with ≥3 tender and swollen joints, elevated C-reactive protein (≥0.3 mg/dL), and radiographic evidence of erosive disease despite prior treatment with a disease- modifying anti-rheumatic drug (DMARD), apremilast, or non- steroidal anti-inflammatory drugs (NSAID) were included. Participants were randomised into 3 arms: guselkumab 100 mg Q4W, guselkumab 100 mg at weeks 0, 4, and then Q8W, or placebo.

At week 24, guselkumab demonstrated a significantly higher American College of Rheumatology (ACR)20 response rate versus placebo, meeting the primary endpoint: 67% and 68% of participants in the guselkumab Q4W and Q8W groups, respectively, compared to 47% in the placebo group (P<0.001 for both). In addition, guselkumab significantly reduced radiographic progression (difference -0.80 vs placebo), a key secondary endpoint. “Participants receiving guselkumab Q4W or Q8W showed a significant structural damage inhibition, including improvements in the joint space narrowing (JSN) score,” Prof. Mease emphasised. Importantly, approximately two-thirds of guselkumab-treated participants showed no radiographic progression, defined as ≤0 change in the PsA- modified van der Heijde-Sharp score, compared to 53% of participants in the placebo arm.

Additional improvements were seen in skin clearance and physical function at week 24 in guselkumab-treated participants. Adverse events occurred in 38% (Q4W), 42%

(Q8W), and 37% (placebo) of participants, with respiratory infections, headache, and diarrhoea being the most common.

“Thus, guselkumab remains the only selective IL-23 inhibitor to date to show significant inhibition of structural damage progression," Prof. Mease concluded, highlighting its potential to alter the trajectory of joint damage in PsA.

1. Van der Heijde D, et Arthritis Res Ther 2020;22:18.
2. Mease PJ, et Lancet 2020;395:e30263-4.
3. Mease 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. LB0010, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 8 August 202525 August 2025