Guselkumab improves biomarkers in TNFi non-responders with psoriatic arthritis
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Key takeaways:
- Guselkumab may improve biomarkers in patients who do not respond to TNF inhibitors.
- Patients receiving guselkumab demonstrated improved biomarkers at week 24.
In patients with psoriatic arthritis and an inadequate response to TNF inhibitors, guselkumab reduces levels of effector cytokines linked to arthritis and skin disease activity, according to data published in Arthritis Research & Therapy.
“Approximately 40% of patients do not achieve 20% improvement in the American College of Rheumatology criteria (ACR20) response within 6 months of treatment of their first [TNF inhibitor (TNFi)],” Georg Schett, MD, of Friedrich-Alexander University, in Germany, and colleagues wrote. “Furthermore, treatment effectiveness and persistence have been shown to decline with successive TNFi treatments.
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“Guselkumab is a high-affinity, fully human, monoclonal antibody that targets the [interleukin (IL)]-23p19 subunit,” they added. “... Previous analyses have shown that C-reactive protein (CRP) and type 17 effector cytokine serum levels are elevated in patients with PsA and can be reduced by inhibiting the IL-23p19 subunit or the IL-12/23p40 subunit.”
To investigate the impact of guselkumab (Tremfya, Janssen) on measurable biomarkers in patients with PsA who saw poor results with a TNF inhibitor, Schett and colleagues analyzed data from COSMOS, a phase 3b, randomized, double-blind trial that enrolled adults with active PsA, including present psoriatic plaque. Participants were randomized 2:1 to receive either guselkumab 100 mg at baseline, week 4 and every 8 weeks thereafter, or placebo. Patients receiving placebo were ultimately switched to guselkumab at week 24, with possible early escape at week 16.
The researchers compared levels of serum cytokines, including interferon (IFN), IL-10, and TNF alpha; T helper 17 (Th17) effector cytokines IL-17A, IL-17F, and IL-22; and acute phase proteins C-reactive protein (CRP), IL-6, and serum amyloid A (SAA) between patients with PsA and demographically matched healthy controls. Additionally, patients in the guselkumab cohort were evaluated using DAS28 scores based on C-reactive protein, swollen joint count and tender joint count. Schett and colleagues also evaluated psoriasis area and severity (PASI) scores, as well as body surface area impacted by psoriatic plaque.
The analysis included 150 patients, of whom 100 were randomized to receive guselkumab.
According to the researchers, patients in the TNF-inhibitor non-responder cohort demonstrated “significantly higher” baseline serum levels of IL-6, IL-10, IL-17A, IL-17F, IL-22, TNF alpha and IFN, compared with matched healthy controls. Levels of IL-17A and IL-17F were linked to baseline PASI scores, as well as psoriasis body surface area scores, Schett and colleagues wrote.
In addition, patients with swollen and tender joints at baseline did not necessarily have higher baseline biomarker levels. Following 24 weeks, “significant” reductions were recorded in biomarkers including CRP, serum amyloid A, IL-17A, IL-17F and IL-22 among patients who received guselkumab, compared with patients who received placebo therapy, according to the researchers.
“Overall, these data suggest that guselkumab reduces the levels of key effector inflammatory cytokines, including those associated with the IL-23/IL-17 pathway, at early time points in participants with TNFi-[inadequate response] PsA,” Schett and colleagues wrote. “Reductions were generally sustained through week 48, with levels of IL-17F, IL-22, CRP, and SAA approximating those observed in healthy controls.”
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