Study Highlights Results of 2 Dosing Regimens of Guselkumab on PsA Symptoms at 24 Weeks

The APEX study is the first to demonstrate that 2 dosing regimens of guselkumab (Q4W and Q8W) significantly inhibit radiographic progression and improve joint symptoms in biologic-naïve patients with active psoriatic arthritis (PsA) by the 24-week mark.1

These data were presented as a poster at the Dermatology Education Foundation (DERM) 2025 NP/PA CME Conference, in Las Vegas, Nevada. Philip J. Mease, MD, a Clinical Professor at the University of Washington School of Medicine and Director of Rheumatology Research at the Swedish Medical Center in Seattle, led the APEX trial investigators in authoring this poster.

Those living with active PsA face high risk of permanent damage to their joints, which Mease and colleagues note can result in a considerable decline in quality of life. Guselkumab is a drug, designed as a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, which has demonstrated both efficacy and a favorable safety profile among those with active PsA.2

“We are now getting more and more choices, so as we strive to get patients into minimal disease activity state and maintain them there, even when we lose effect with one drug or one mechanism, we've now got others to be able to cycle to, and that's very helpful for us,” Mease told HCPLive in a recent interview.2

The interim results of APEX through Week 24 in the ongoing phase 3b APEX trial (NCT04882098) study provide insights into the clinical and radiographic effects of guselkumab in individuals with active PsA. The trial has a randomized, double-blind, placebo-controlled trial design.

Biologic-naïve adults with active PsA were recruited, with active disease being defined by Mease et al as having a C-reactive protein (CRP) level ≥0.3 mg/dL, reporting at least 3 tender and 3 swollen joints, and showing radiographic evidence of erosion in 2 joints minimum of the hands or feet.

Those enrolled as subjects, all of whom had previously been given treatment with non-biologic DMARDs, apremilast, or NSAIDs, were randomized in a 5:7:7 ratio to receive 1 of 3 potential regimens: subcutaneous guselkumab 100 mg Q4W, 100 mg at Weeks 0 and 4 followed by Q8W, or a placebo Q4W. In their co-primary outcomes, the investigators looked at the proportion of patients at Week 24 who attained at least 20% improvement in American College of Rheumatology criteria (ACR20) and the mean change from the point of baseline in patients' PsA-modified van der Heijde-Sharp (vdH-S) scores.

The latter endpoint was assessed by 2 independent blinded readers. Both endpoints were adjusted by Mease and coauthors for multiplicity across each medication regimen versus placebo.

The investigative team's safety analysis included all subjects who were treated with at least a single dose of guselkumab through the 24-week mark (N=1054). The team highlighted that the average age of subjects was 53 years, with 55% being listed as male. At study entry, the mean duration of PsA was 7.3 years. Severity of PsA was shown to be notable, with Mease and coauthors finding that the mean PsA-modified vdH-S total and erosion scores were 27.0 and 13.5, respectively.

The investigators also found that mean tender and swollen joint counts were 20.7 and 11.9, respectively. Overall, the primary and major secondary endpoints were met, with 24-week ACR20 responses being significantly higher in the Q4W (67%) and the Q8W (68%) treatment arms versus those in the placebo arm (47%), with p-values <0.001 for both comparisons.1

In terms of structural damage, the Q4W and Q8W patient cohorts were found to have significantly less radiographic progression than participants in the placebo cohorts, as reflected by least squares mean changes in vdH-S scores of 0.55 and 0.54 versus 1.35 (P = .002 and P < .001, respectively). Comparable patterns of benefit were observed in erosion scores, joint space narrowing, the proportion of subjects without radiographic progression, and additional clinical endpoints.

The investigative team determined that incidence of adverse events (AEs) was similar across the cohorts, with 38% in the guselkumab Q4W arm, 42% in the Q8W arm, and 37% in the placebo arm. In their evaluation of the most frequent AEs, examples included headaches, respiratory tract infections, diarrhea, and psoriatic arthropathy. Serious AEs were reported in 2% (Q4W), 3% (Q8W), and 3% (placebo) of individuals in the study, yet no new safety concerns were identified by Mease and colleagues.

References

1. Mease PJ, Ritchlin CT, Coates LC, et al. 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. Presented at DERM 2025 NP PA CME Conference; July 23-26, 2025; Las Vegas, Nevada.

2. Johnson V. J&J Seeks New Guselkumab Label Reflecting Inhibition of PsA Joint Damage. HCPLive. July 29, 2025. Accessed August 8, 2025. https://www.hcplive.com/view/j-j-seeks-new-guselkumab-label-reflecting-inhibition-of-psa-joint-damage.