Q&A: How Trial Enrichment Shaped APEX's Radiographic Findings in Psoriatic Disease

The US Food and Drug Administration (FDA) approved a label update for guselkumab (Tremfya) in May 2026, crediting the phase 3b APEX trial (NCT04882098) with inhibiting radiographic joint damage in psoriatic arthritis.¹ David Oberlin, MD, dermatologist at Forefront Dermatology in Grand Rapids, Michigan, and Jesse Veenstra, MD, PhD, of Henry Ford Health, co-authored a commentary on the findings in the Journal of the American Academy of Dermatology.² The pair questioned whether APEX's enriched population reflects general dermatology patients.

"The most informative trial is not necessarily the one with the largest effect, but the one whose participants most closely resemble the patient being treated," said Oberlin. APEX enrolled biologic-naive patients with erosive disease, elevated CRP, and PsA duration beyond 6 months, criteria far more restrictive than those used in comparator trials such as DISCOVER-2 and KEEPsAKE 1.

Baseline joint damage closely tracked placebo-arm progression on radiographic Sharp scores across trials, with a near-linear correlation of 0.97.² This made a statistically significant treatment effect easier to reach in a more enriched population, regardless of drug mechanism. DISCOVER-2 carried some baseline enrichment of its own, Oberlin noted, but APEX pushed enrichment further to widen the placebo-progression gap.

This relationship helps explain why APEX reached significance on its radiographic endpoint while DISCOVER-2, also testing guselkumab, and KEEPsAKE 1, testing risankizumab (Skyrizi), did not, despite both drugs working through interleukin-23 inhibition.³ No head-to-head trial has directly compared the two drugs on joint damage outcomes, Oberlin noted. In the following interview, Oberlin discusses how trial design, rather than drug mechanism, shaped APEX's radiographic results.

HCPLive: Can you walk me through the core takeaway you and your co-author wanted dermatologists to take from this commentary?

David Oberlin, MD: I think the big thing Dr. Veenstra and I were looking at is, with this label update for guselkumab following the APEX trial demonstrating radiographic inhibition of joint disease in patients with PsO and PsA, what we really wanted to analyze is whether this applies to general dermatology patients. After we looked at the data and the enrichment of the baseline characteristics of these patients, we wanted to make sure we were better educating providers regarding these enrichment strategies and asking whether this particular study applies to our patients in general dermatology.

HCPLive: Why does APEX's baseline erosive-disease requirement matter when comparing radiographic results across trials?

David Oberlin, MD: Because of what we've seen in a regression plot with a correlation of almost 1, at 0.97, it's almost a straight line: the more baseline disease these patients have, the more placebo progression they will have over that 24-week period, with BE OPTIMAL only being a 16-week period. The higher the baseline joint disease, the more likely the placebo group is to progress in terms of Sharp scores. This allows for a statistically significant difference between baseline characteristics and the treatment arm, so by enriching for placebo progression, you're able to show statistical significance for the treatment arm.

HCPLive: What does the correlation between baseline joint damage and placebo progression tell us about differing treatment effects across trials?

David Oberlin, MD: Not all IL-23 agents are created equally, and we know that with the IL-17 inhibitors as well; there are different nuances and different binding capacities. We don't necessarily have head-to-head data, and that's really the key for us to be able to tell these drugs apart. But what we can say is that in this specifically enriched population with APEX, they show statistical significance, whereas the other interleukin-23 agents, specifically guselkumab in DISCOVER-2 and risankizumab in KEEPsAKE, are not showing statistical significance, simply because the lack of placebo progression did not allow for that delta from the treatment arm.

Editor’s note: Oberlin disclosed having received honoraria for serving as a key opinion leader for Amgen, AbbVie, UCB, and Arcutis, and for participating on advisory boards for AbbVie, Sensus, UCB, Sanofi, Incyte, and Apogee. This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Johnson & Johnson. FDA approves label expansion, cementing TREMFYA as the only IL-23 inhibitor proven to help stop further joint damage. Published May 28, 2026. Accessed September 14, 2026. https://www.jnj.com/media-center/press-releases/fda-approves-label-expansion-cementing-tremfya-as-the-only-il-23-inhibitor-proven-to-help-stop-further-joint-damage.

2. Oberlin D, Veenstra J. Interpreting radiographic outcomes across IL-23 inhibitor trials in psoriatic arthritis: the role of trial design. J Am Acad Dermatol. Published online July 3, 2026. doi:10.1016/j.jaad.2026.06.135.

3. Mease PJ, Ritchlin CT, Coates LC, et al. Inhibition of structural damage progression with the selective interleukin-23 inhibitor guselkumab in participants with active PsA: results through week 24 of the phase 3b, randomized, double-blind, placebo-controlled APEX study. Ann Rheum Dis. 2025:S0003-4967(25)04305-5. doi:10.1016/j.ard.2025.08.006.