Guselkumab's CD64 Binding Offers Targeted IL-23 Inhibition in PsA

“It's a good time for us in both dermatology and rheumatology to be treating our patients because we have some very good options for treatment to try to achieve either remission of disease activity or low disease activity states, and really try to give the patient back their life. It's rewarding to be able to work with patients and see the kind of improvements that are occurring and celebrate that with them,” said Philip Mease, MD.

Mease, a rheumatologist and director of rheumatology research at Providence Swedish Medical Center in Seattle, discussed the FDA's recent label expansion for guselkumab (Tremfya; Johnson & Johnson) in psoriatic arthritis. The approval adds inhibition of structural joint damage progression to the drug's label, based on data from the phase 3b APEX trial (NCT04882098).¹ Mease explained guselkumab’s binding to CD64 receptors and how it contributes to IL-23 inhibition.

In a previous interview, Mease addressed the rationale for treating psoriatic arthritis early with biologic therapy and what delayed-switch data from APEX show about guselkumab's effect once disease progression has already begun.

Targeted IL-23 Neutralization at the Site of Inflammation

Guselkumab binds to CD64 receptors on monocytes and other immune cells present at sites of active inflammation, whether in the joints or skin, according to Mease. This dual mechanism allows the drug to intercept IL-23 close to where it is produced rather than only in systemic circulation. Mease said this localized activity distinguishes guselkumab's approach to IL-23 inhibition.

"It's acting in the room where it's happening," Mease said, comparing the drug's local activity to a phrase from the musical Hamilton. The medication binds IL-23 as monocytes and other cells emit it at the inflammatory site, neutralizing the cytokine close to its source, Mease said.

FDA Label Expansion for Structural Damage Inhibition

Approximately 30% of patients with psoriasis develop psoriatic arthritis, Mease said, making the condition an important consideration for dermatologists managing psoriasis treatment. Patients may not always report musculoskeletal symptoms during dermatology visits, but the possibility of joint involvement remains relevant to treatment discussions, he said.

"It should be top of mind for dermatologists when they're thinking about treatment for their psoriasis patients and making suggestions," Mease said.

Mease said dermatologists are not expected to assess joints or order imaging themselves, but awareness of a treatment option with demonstrated inhibition of structural damage progression can inform referral and treatment conversations. He noted the dosing schedule, administered once every 2 months, as an additional consideration for patients.

"Here, I've got a choice of using a pretty safe medication," Mease said. "It's conveniently only given once every 2 months."

Mease described the current period as a positive time in both dermatology and rheumatology, with treatment options capable of achieving remission or low disease activity for many patients.

Reference

1. FDA approves label expansion, cementing Tremfya as the only IL‑23 inhibitor proven to help stop further joint damage. News release. Johnson & Johnson. May 28, 2026. Accessed July 10, 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