Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

RMD Open. 2021 May;7(2):e001679. doi: 10.1136/rmdopen-2021-001679.


Objective: To investigate serum protein expression in participants with psoriatic arthritis (PsA) and changes after guselkumab treatment.

Methods: Participants with PsA were treated with guselkumab or placebo in the DISCOVER-1 and DISCOVER-2 studies. Serum levels of acute phase reactants C reactive protein (CRP) and serum amyloid A (SAA) and inflammatory cytokines/chemokines were measured at weeks 0, 4 and 24 in 300 study participants and 34 healthy controls (HCs). The PSUMMIT studies measured serum interleukin (IL)-17A, IL-17F and CRP after ustekinumab treatment and levels with ustekinumab versus guselkumab treatment were compared.

Results: Baseline serum levels of CRP, SAA, IL-6, IL-17A and IL-17F were elevated in participants with active PsA vs HCs (p<0.05, geometric mean (GM) ≥40% higher). Baseline T-helper cell 17 (Th17) effector cytokines were significantly associated with baseline psoriasis but not joint disease activity. Compared with placebo, guselkumab treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F and IL-22 as early as week 4 and continued to decrease through week 24 (p<0.05, GM decrease from baseline ≥33%). At week 24, IL-17A and IL-17F levels were not significantly different from HCs, suggesting normalisation of peripheral IL-23/Th17 axis effector cytokines postguselkumab treatment. Reductions in IL-17A/IL-17F levels were greater in guselkumab-treated versus ustekinumab-treated participants, whereas effects on CRP levels were similar.

Conclusion: Guselkumab treatment reduced serum protein levels of acute phase and Th17 effector cytokines and achieved comparable levels to those in HCs. In participants with PsA, reductions of IL-17A and IL-17F were of greater magnitude after treatment with guselkumab than with ustekinumab.

Trial registration: NCT03162796 NCT03158285.

Keywords: Arthritis; Biological Therapy; Cytokines; Psoriatic.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Psoriatic* / drug therapy
  • Cytokines
  • Double-Blind Method
  • Humans
  • Severity of Illness Index
  • Treatment Outcome


  • Acute-Phase Proteins
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • guselkumab

Associated data