Q&A: Why APEX May Not Prove Guselkumab is Superior for PsA Joints

Guselkumab (Tremfya) and risankizumab (Skyrizi), both interleukin (IL)-23 inhibitors, maintain different radiographic track records in psoriatic arthritis (PsA). Guselkumab's phase 3b APEX trial (NCT04882098) met its radiographic endpoint, whereas risankizumab's KEEPsAKE 1 trial did not, despite both drugs sharing the same mechanism of action.¹ No head-to-head trial has compared the 2 drugs directly on joint damage outcomes.

DISCOVER-2, also testing guselkumab, carried some baseline enrichment of its own but fell short of the placebo-arm progression APEX generated, according to an analysis of the 3 trials.² The gap left DISCOVER-2 without a statistically significant radiographic finding, even under the same drug and mechanism as APEX.

David Oberlin, MD, dermatologist at Forefront Dermatology in Grand Rapids, Michigan, examined this pattern in a commentary published in the Journal of the American Academy of Dermatology.² His co-author was Jesse Veenstra, MD, PhD, of Henry Ford Health. Oberlin cautioned against reading APEX's radiographic result as evidence of mechanistic superiority over risankizumab, pointing instead to differences in trial enrollment.

APEX required elevated CRP, erosive disease at baseline, PsA duration beyond 6 months, and a biologic-naive population, criteria he said he rarely sees met together in general dermatology practice. "The biggest message we want to get across to providers is make sure the baseline characteristics of the trial represent the patient in front of you," Oberlin said.

Choosing among IL-23 and IL-17 agents for PsA still comes down to disease severity, comorbidities, desired speed of clearance, oral versus injectable preference, dosing frequency, and formulary coverage, he added. In the following interview, Oberlin discussed with HCPLive what dermatologists should weigh when a patient in front of them does not resemble the enriched APEX population.

HCPLive: If a colleague said guselkumab is more effective than risankizumab at stopping joint damage, how would you respond?

David Oberlin, MD: I don't think we have that data. There is no head-to-head data between the two products. Especially what I would compare is what patients were enrolled in the trial. Again, the enrichment strategy requiring elevated CRP, erosive disease at baseline, greater than six months duration, being biologic-naive. In general dermatology practice, in 10 years of practice, I've never seen a patient that meets all of these criteria.

So it's not something necessarily that's going to be walking into my clinic. That more general PsO-PsA overlap is more represented in the KEEPsAKE trial and BE OPTIMAL trial. Even DISCOVER-2 had some baseline enrichment; if you see how we plotted it out, there was some enrichment in terms of the baseline Sharp score characteristics. So APEX just took that to the next level to allow for the placebo progression to show that statistically significant delta from placebo.

HCPLive: What should dermatologists actually weigh when choosing a biologic for a patient with PsA?

David Oberlin, MD: There's a number of things we have to take into account. First of all, do they want an oral option or an injectable option? We have several oral therapies that we can use that are FDA-approved for psoriasis, though not all of them are approved for psoriatic arthritis yet. We also have several injectable options. I'm not anti-guselkumab; I think it's a fantastic molecule, and I use a lot of the IL-23 agents in my practice, along with a lot of the IL-17 agents. So I think we're very blessed in dermatology to have a lot of meaningful therapeutic options. But take multiple factors into account: how severe the patient is, what their other comorbid conditions are, whether they want pills or shots, how rapidly they need to clear, whether they want less frequent dosing.

There's a lot of different factors to consider, and ultimately coverage can make a difference too, since formulary coverage matters for many of these patients. But I don't necessarily think APEX specifically is going to move the needle one way or the other for me. Again, the biggest message we want to get across to providers is to make sure the baseline characteristics of the trial represent the patient in front of you. If the patient in front of you fits the APEX trial, you may be able to inhibit radiographic progression, but otherwise you cannot look at that study and say it has mechanistic superiority compared to other IL-23 agents.

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. Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022;81(2):225-231. doi:10.1136/annrheumdis-2021-221019.

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.