Secukinumab produces a quick increase in WNT signalling antagonists in patients with psoriatic arthritis

Clin Exp Rheumatol. 2019 Jan-Feb;37(1):133-136. Epub 2018 Oct 23.

Abstract

Objectives: Interleukin-17 (IL-17) is an important cytokine involved in the pathogenesis of bone lesions of psoriatic arthritis (PsA). The aim of our study was to explore the short-term effects (≤6 months) of secukinumab (an anti-IL-17 antibody) on the serum levels of bone turnover markers (BTMs) and on the inhibitors of the WNT signalling pathway.

Methods: The study sample consisted of patients with PsA starting treatment with secukinumab 150 mg every month, and healthy controls (HCs). For the PsA group, the DAS28 score was recorded, and serum samples were collected at baseline, and then at Month 1, 3 and 6 of therapy. As for the HCs, a single observation was performed, with the relevant serum collection. Intact N-terminal propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (CTX-I-I), Dickkopf-related protein-1 (Dkk-1) and sclerostin were administered.

Results: 28 patients with PsA and 43 HCs were enrolled. Neither PINP nor CTX-I serum levels showed any significant variation during the observation period. Baseline mean Dkk-1 serum levels for the PsA arm were significantly lower than in the HC (p<0.05). Dkk-1 and sclerostin serum levels increased at Month 6 during the treatment with secukinumab (p<0.05 vs. baseline). When the PsA arm was compared to the HC, the difference between the serum levels of Dkk-1 lost significance at Month 6.

Conclusions: Treatment with secukinumab does not have any significant short-term effect on BTMs, but may influence some fine regulators of the bone cell activity, such as the WNT inhibitors.

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Psoriatic* / drug therapy
  • Biomarkers
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interleukin-17 / antagonists & inhibitors*
  • Wnt Signaling Pathway* / drug effects

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-17
  • secukinumab