Guselkumab Produces Long-Lasting Pharmacodynamic Effects, Disease Improvement in PsA

In a cohort of biologic-naïve patients with active psoriatic arthritis (PsA), sustainable pharmacodynamic effects, improvements in disease activity, and significant reductions in serum cytokines and collagen degradation proteins were observed in patients receiving long-term guselkumab treatment, which were maintained through week 100, according to research presented at the 2023 Congress of Clinical Rheumatology West.¹

Stefan Siebert, PhD

Credit: University of Glasgow

“This analysis assessed the long-term effects of guselkumab on serum cytokine and collagen proteins and explored the associations between biomarker levels and longer-term clinical responses through week 100,” wrote lead investigator Stefan Siebert, PhD, professor of inflammation medicine and rheumatology at the University of Glasgow and honorary consultant rheumatologist with NHS Greater Glasgow and Clyde, and colleagues.

The phase 3 DISCOVER-2 trial enrolled biologic-naïve patients with active PsA and randomized them to receive guselkumab 100 mg at week 0 and then every 4 weeks (Q4W), guselkumab 100 mg at week 0, week 4, and then every 8 weeks (Q8W), or placebo. Those in the treatment cohorts demonstrated significantly reduced signs and symptoms of disease when compared with the placebo, with durable response rates among multiple disease domains and low rates of radiographic progression through week 100.

In addition, guselkumab treatment significantly decreased the serum levels of collagen proteins, which is often elevated in this patient population. Changes in these and other serum cytokine levels at the 24-week mark were linked to clinical response through 2 years.

Patients included in this analysis were chosen based on sample availability as well as baseline demographic and disease characteristics in the overall guselkumab-treated population. Of these, 100 patients were included in the serum biomarker group and 178 patients were included in the collagen protein group. Serum samples were collected at baseline, week 4, week 24, week 52, and week 100.

Disease activity and clinical response were based on the Psoriatic Area and Severity Index (PASI) score, Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity in Psoriatic Arthritis (DAPSA) score, and ≥50% improvement in the American College of Rheumatology criteria (ACR50) response.

Reductions in markers of collagen degradation were revealed through week 100 in patients receiving guselkumab, with notable reductions in C1M and C6M levels. Reductions in serum biomarkers were linked to improvements in disease activity at week 24, week 52, and week 100.

Greater reductions in acute phase proteins and collagen degradation proteins in ACR50 non-responders at week 24 who achieved ACR50 at week 100 demonstrated continued improvement in disease activity with long-term guselkumab treatment. Reductions in interleukin (IL)-6 and C-reactive protein were linked to improvements in DAPSA and PASDAS scores, while reductions in IL-17A, IL-22, IL-17F, and β-Defensin 2 (BD-2) were associated with PASI score improvements.

In addition to these results, other research presented at the conference revealed guselkumab treatment improved the activities of daily living in this patient population. Of the items most impaired at baseline, as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), a higher number of patients receiving guselkumab treatment reported ≥1 improvement as early as week 4, which continued to improve through week 24.²

“These results provide molecular evidence that sustained reductions in serum acute phase proteins and collagen degradation proteins seen with guselkumab treatment may contribute to continuous and durable improvements in joint symptoms, consistent with clinical observations in guselkumab-treatment patients through week 100 in DISCOVER-2,” concluded investigators. “Furthermore, the reductions in Th17-related effector cytokines and BD-2 may contribute to durable improvements in skin symptoms seen in patients with PsA treated with guselkumab.”

References

1. ^{Siebert S, Schett G, Raychaudhuri S, Guma, M, et al. Changes in Serum Cytokines and Collagen Proteins Correlate with Durability of Guselkumab Efficacy and Continued Disease Improvement Through 2 Years in Patients with Active Psoriatic Arthritis. Congress of Clinical Rheumatology. September 2023.}
2. ^{Pine, L. (2023, September 8). Guselkumab quickly improves activities of daily living in patients with PSA. HCP Live. https://www.hcplive.com/view/guselkumab-quickly-improves-activities-of-daily-living-in-patients-with-psa}