Rapid radiographic improvement with IL-23 blockade in biologic-naïve PsA patients

A 24-week analysis of the phase 3b APEX study showed that guselkumab, a monoclonal antibody targeting the IL-23p19 subunit, significantly inhibits structural joint damage and improves clinical outcomes in biologic-naïve patients with active psoriatic arthritis (PsA).

In the earlier DISCOVER-2 trial, biologic-naïve participants with active PsA receiving guselkumab every 4 weeks (Q4W) but not every 8 weeks (Q8W) exhibited significantly less radiographic progression over placebo [1]. “So, the goal of this phase 3b study is to more closely evaluate the ability of both Q4W and Q8W regimens to prevent structural progression”, explained Prof. Philip J. Mease (Swedish Medical Center, Seattle, USA) [2].

In the ongoing APEX trial (NCT04882098), 1020 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 DMARD, apremilast, or 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 ACR20 response rate versus placebo, meeting the primary endpoint. Response rates were  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 comparisons). In addition, guselkumab significantly reduced radiographic progression (D -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, a higher proportion of participants treated with guselkumab experienced no radiographic progression by week 24. “Two-thirds of participants achieved a ≤0 change in the PsA-modified van der Heijde-Sharp score”, Prof Mease added. Consistent benefits were seen in erosion and joint narrowing space scores.

Additional improvements were seen in skin clearance and physical function at week 24 in guselkumab-treated patients. 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 that has shown significant inhibition of structural damage progression”, Prof. Mease concluded.

1. Mease PJ, et al. Lancet 2020;395:e30263-4.
2. Mease PJ. 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 18 June 20258 August 2025