Modulation of IL-23 Signaling With Guselkumab in Biologic-Naïve Patients Versus TNF Inhibitor-Inadequate Responders With Active Psoriatic Arthritis.

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Arthritis Rheumatol


washington; swedish


OBJECTIVE: Assess and compare immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)-23p19-subunit inhibitor, in participants with active PsA who were biologic-naïve or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

METHODS: Serum biomarker levels at baseline and following treatment with guselkumab 100 mg Q8W were compared between biologic-naïve (N=251) and TNFi-IR (N=93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS dataset. Baseline biomarker levels determined by achievement of Week-24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between subgroups.

RESULTS: Baseline IL-22, TNFα, and beta defensin (BD)-2 levels were significantly lower in biologic-naïve than in TNFi-IR participants. With guselkumab, Week-24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naïve and TNFi-IR participants (≥1.4-fold difference, nominal P

CONCLUSION: Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naïve and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses with guselkumab suggest greater dysregulation of IL-23/Th17 signaling in TNFi-IR patients.

Clinical Institute

Orthopedics & Sports Medicine