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

Abstract

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: ClinicalTrials.gov NCT03162796 NCT03158285.

Keywords: Arthritis; Biological Therapy; Cytokines; Psoriatic.

Conflict of interest statement

Competing interests: KS, QS, MJL, KM, KL, VL, CF and PC are employees of Janssen Research & Development, a wholly owned subsidiary of Johnson & Johnson and own company stock. SS, FRCP, PhD has received research grants, consulting fees and/or honoraria (all <US$10 000 per annum) from AbbVie, Amgen (previously Celgene), Biogen, Janssen, and Novartis. Iain B. McInnes, FRCP, PhD has received research grants, consulting fees, and/or honoraria (all US$<10 000 per annum) from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, GSK, Janssen, Novartis, Pfizer, Sanofi and UCB.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Baseline levels of acute phase reactants (A–C) and IL-23/Th17 effector cytokines (D–F) in patients with PsA in DISCOVER studies compared with matched healthy controls. Concentration (log2) of analyte (indicated at top of plots) for PsA patients (baseline) and healthy controls. Data presented as symbols representing individual participants and summarised by box plots. Each box represents the upper and lower IQR; lines inside the boxes represent the median; and whiskers represent the range. *Generalised linear model p<0.05 and absolute value of fold difference ≥1.4 vs healthy controls. CRP, C reactive protein; IL, interleukin; PsA, psoriatic arthritis; SAA, serum amyloid A; Th17, T-helper cell 17.

Figure 2

Boxplots of Baseline IL-17A (A) (p=0.0432) and IL-17F (B) (p=0.0222) levels in PASI75 guselkumab non-responders (open circles) and guselkumab responders (grey) at week 24. Each box represents the upper and lower IQR; lines inside the boxes represent the median; and whiskers represent the range. IL interleukin; PASI, Psoriasis Area and severity index.

Figure 3

Change in serum CRP (A), SAA (B), IL-6 (C), IL-17A (D), IL-17F (E) and IL-22 (F) levels in PsA patients in response to treatment with guselkumab compared with placebo over 24 weeks. *P≤0.05 vs baseline, fold difference ≥1.4; #p≤0.05 vs PBO, fold difference ≥1.4; error bars represent two SEs of the mean (~95% CI). BL, baseline; CRP, C reactive protein; GUS, guselkumab; IL, interleukin; PBO, placebo; PsA, psoriatic arthritis; SAA, serum amyloid A; qw4, every 4 weeks; qw8, every 8 weeks; Wk, week.

Figure 4

Comparison of changes in serum CRP (A), IL-17A (B) and IL-17F (C) levels with guselkumab (data from DISCOVER-1 and DISCOVER-2 phase 3 studies) and ustekinumab (data from PSUMMIT-1 and PSUMMIT-2 phase 3 studies) over 24 weeks. CRP, C reactive protein; IL, interleukin; PsA, psoriatic arthritis; Wk, week.