Guselkumab Decreases Levels of Collagen-Degrading Biomarkers in Patients With PsA

Concentrations of serum collagen biomarkers associated with collagen degradation (C1M, C3M, C4M, and C6M) were significantly higher in patients with psoriatic arthritis (PsA) when compared with healthy controls, according to a study published in Springer.¹ Treatment with guselkumab, a novel interleukin-23p19 subunit monoclonal antibody, decreased levels of these biomarkers, with C1M closely linked to improvement in joint signs and symptoms.

“Biomarkers can be used to elucidate normal and pathological processes and to measure biological response to a therapeutic intervention,” investigators stated. “In PsA, there is a clear unmet medical need for biomarkers that can characterize patients and identify which therapy may provide the most benefit for a particular patient.”

In the double-blind, randomized, placebo-controlled, phase 3 DISCOVER-2 (NCT03158285) trial, investigators analyzed serum concentrations of extracellular matrix (ECM) biomarkers associated with both collagen degradation (C1M, C2M, C3M, C4M, C6M, C10C) and collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6) both at baseline and after initiating guselkumab treatment in a subset (n = 260 out of 739) of biologic-naïve patients with active PsA. Samples were collected at baseline, week 4, week 24, and week 52.

Patients received guselkumab 100 mg every 4 weeks (Q4W, n = 82), 8 weeks (Q8W, n = 92), or placebo (n = 86), and were compared with age- and gender-matched healthy controls (n = 76). Demographics and disease characteristics ensured that the subset group was reflective of the entire study population.

At baseline, collagen degradation biomarkers (C1M, C3M, C4M, and C6M) as well as collagen formation biomarkers (PRO-C3 and PRO-C6) were significantly higher in patients with PsA (i.e., ≥ 1.25-fold and adj p < 0.05).

After initiating treatment, C1M, C3M, C4M, and C6M levels decreased in both groups receiving the drug. At week 24, patients receiving guselkumab (either Q4W or Q8W) were more likely to achieve ≥ 20% improvement in American College of Rheumatology response criteria (ACR20) when compared with the placebo cohort (67%, 59%, and 26%, respectively). Both guselkumab groups were more likely to reach ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI75) responses when compared with placebo (78% vs 24%, respectively). Patients who obtained ACR20 tended to have significantly lower C1M levels when compared with non-responders (−1.26-fold; adj p = 0.0065).

As investigators evaluated collagen biomarker levels via serum, additional large cohort studies are needed to understand the collagen turnover in affected tissues. Future work should also explore the relationship of these biomarkers to PsA specifically, including other characteristics that may affect levels, such as diet, genetics, and environment.

“The need for surrogate blood-based biomarkers of the joint to provide a more granular understanding of disease progression or improvement to support PsA patient care and clinical trials of new therapies is clear, and the results of this study suggest that serum collagen degradation and formation biomarkers have potential as PsA biomarkers,” investigators concluded. “This work provides insight into the potential utility of ECM biomarkers in PsA patients and evidence that guselkumab may decrease collagen turnover.”

Reference:

Schett G, Loza MJ, Palanichamy A, et al. Collagen Turnover Biomarkers Associate with Active Psoriatic Arthritis and Decrease with Guselkumab Treatment in a Phase 3 Clinical Trial (DISCOVER-2) [published online ahead of print, 2022 Mar 30]. Rheumatol Ther. 2022;10.1007/s40744-022-00444-x. doi:10.1007/s40744-022-00444-x