Study Pinpoints Candidiasis Risk With Dual IL-17A/F Blockade

TOPLINE:

Drugs that simultaneously block interleukin (IL)-17A and IL-17F reduced the movement of protective white blood cells, making it harder for them to clear fungal infections and resulting in a higher risk for mucosal and systemic candidiasis in people taking them, according to results of an in vitro study. The finding helped explain why patients with psoriasis and psoriatic arthritis taking bimekizumab, an IL-17A/IL-17F blocking agent, have been reported to have high rates of fungal infections.

METHODOLOGY:

• Blood was drawn from 10 patients with psoriatic arthritis and centrifuged to isolate neutrophils.
• Chemotaxis assays were performed to measure neutrophil migration based on their optical density in the presence of different combinations of the cytokines IL-17A and IL-17F and anti-IL-17A and anti-IL-17F monoclonal antibodies.
• Candida cells were added to samples to assess how the neutrophils and the Candida interacted under the different cytokine and antibody combinations.

TAKEAWAY:

• Neutrophil chemotaxis was significantly greater in the presence of either cytokine on its own vs its combination with its respective monoclonal antibody, and this effect was most pronounced in the presence of both cytokines together vs a combination of both monoclonal antibodies.
• IL-17A and IL-17F reduced Candida survival both on their own and synergistically when together by inducing neutrophil chemotaxis. This effect was neutralized by the presence of anti-IL-17A and anti-IL-17F monoclonal antibodies separately or together, leading to increased survival of Candida.

IN PRACTICE:

“Clinical trials and post-marketing surveillance of bimekizumab saw higher candidiasis,” said Disha Chakraborty, who presented the results at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2025 Annual Meeting and Trainee Symposium in Bogotá, Colombia. “We thought it might be because of the [effect on] neutrophil chemotaxis, and the results exactly translated to that. However, bimekizumab also has very good efficacy in PsA [psoriatic arthritis]. So we need to balance efficacy with increased monitoring of patients.”

SOURCE:

The poster “Exploring the Synergistic Effects of IL-17A and IL-17F on Neutrophil Chemotaxis: Risk of Candidiasis with Dual Blockade of IL-17A and IL17-F” was presented at GRAPPA 2025 by Chakraborty, who at the time of the study was a postdoctoral research fellow in the Division of Rheumatology & Immunology, Veterans Affairs Medical Center, Mather, California.

LIMITATIONS:

The study sample size was small. The experiments comprised translational research exploring the reasons behind higher candidiasis rates with dual IL-17A/IL-17F blockers. The results do not necessarily correspond with the nature or extent of clinical candidiasis that may occur in patients taking these therapies.

DISCLOSURES:

The authors disclosed having no financial conflicts of interest.