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. 2024 Mar 5;25(5):3002.
doi: 10.3390/ijms25053002.

Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients

Marie Skougaard  1   2   3 , Magnus Friis Søndergaard  2 , Sisse Bolm Ditlev  2 , Lars Erik Kristensen  1   4
Affiliations

Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients

Marie Skougaard et al. Int J Mol Sci. .

Abstract

This study aimed to examine the changes in biomarker levels in responders and non-responders to tumor necrosis factor alpha inhibitor (TNFi) and interleukin-17A inhibitor (IL-17Ai) in psoriatic arthritis (PsA) patients over a 4-month period after treatment initiation. A total of 68 PsA patients initiating either TNFi, IL-17Ai, or methotrexate treatment were included. Blood plasma and clinical outcome measures were collected adjacent to treatment initiation and after four months. A commercially available multiplex immunoassay was included to evaluate 54 biomarkers. Mean changes were used to evaluate change over time. A statistically significant decrease in pro-inflammatory cytokines IL-6 (log-transformed mean change -0.97, 95%CI -4.30; 2.37, [p = 0.032]) and an increase in anti-inflammatory IL-10 (0.38, 95%CI 1.74; 2.50 [p = 0.010]) were seen in TNFi responders. Meanwhile, a statistically significant increase in the target cytokine IL-17A was seen in both IL-17Ai responders (2.49, 95%CI -1.84; 6.85 [p = 0.031]) and non-responders (2.48, 95%CI -1.46; 6.41 [p = 0.001]). This study demonstrated differing changes in cytokine levels when comparing treatment responders and non-responders, highlighting the need to improve the understanding of the different immune response mechanisms explaining different responses to medical treatment in PsA patients.

Keywords: IL-17A; TNFα; bDMARDs; cytokine; psoriatic arthritis.

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Conflict of interest statement

Marie Skougaard has received research funding from the Danish Rheumatism Association, the Danish National Psoriasis Foundation, Lilly and Pfizer, and a speaker fee from Janssen-Cilag. Sisse B. Ditlev has no conflicts of interest. Magnus Friis Søndergaard has no conflicts of interest. Lars Erik Kristensen has received fees for speaking and consultancy from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, and UCB, as well as IIT grants from Biogen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Correlation analysis. Spearman’s correlation coefficient was implemented to assess associations between individual biomarkers and clinical and patient-reported outcomes. SJC, swollen joint count; TJC, tender joint count; SPARCC, Spondyloarthritis Research Consortium of Canada; PASI, Psoriasis Area Severity Index; DAS28CRP, Disease Activity Score calculated with 28 joints and c-reactive protein; DAPSA, disease activity in psoriatic arthritis; bFGF, basic fibroblast growth factor; Flt-1, Fms-related receptor tyrosine kinase-1; PlGF, placental growth factor; Tie-2, endothelial receptor tyrosine kinase; VEGF, vascular endothelial growth factor; IP-10, IFN-induced protein-10; MCP, monocyte chemoattractant protein; MDC, macrophage-derived chemokine; MIP, macrophage inflammatory protein; TARC, thymus and activation-regulated chemokine; IL, interleukin; IL-1RA, interleukin-1 receptor antagonist; IFN, interferon; TNF, tumor necrosis factor; CRP, c-reactive protein; ICAM, intercellular adhesion molecule; VCAM, vascular cell adhesion molecule.
Figure 2
Figure 2
Mean changes in biomarker levels in TNFi initiators stratified by DAPSA50. Log-transformed mean changes from baseline to four-month follow-up stratified by DAPSA50 corresponding to a 50% improvement in DAPSA, included as a measure of arthritic joint disease (Table S2). * (star) represents changes that are statistically significant. TNFi, tumor necrosis factor alpha inhibitor; DAPSA, disease activity in psoriatic arthritis; VEGF, vascular endothelial growth factor; VCAM, vascular cell adhesion molecule; TNF, tumor necrosis factor; Tie-2, endothelial receptor tyrosine kinase; TARC, thymus and activation regulated chemokine; CCL, CC chemokine ligand; SAA, serum amyloid A; PlGF, placental growth factor; MIP, macrophage inflammatory protein; MDC, macrophage-derived chemokine; MCP, monocyte chemoattractant protein; IP-10, IFN-induced protein-10; CXCL, CX chemokine ligand; IL, interleukin; IL-1RA, interleukin-1 receptor antagonist; IFN, interferon; ICAM, intercellular adhesion molecule; Flt-1, Fms-related receptor tyrosine kinase-1; CRP, c-reactive protein; bFGF, basic fibroblast growth factor.
Figure 3
Figure 3
Mean changes in biomarker level in IL-17Ai initiators stratified by DAPSA50. Log-transformed mean changes from baseline to four-month follow-up stratified by DAPSA50 corresponding to a 50% improvement in DAPSA, included as a measure of arthritic joint disease (Table S3). * (star) represents changes that are statistically significant. IL-17Ai, interleukin-17A inhibitor; DAPSA, disease activity in psoriatic arthritis; VEGF, vascular endothelial growth factor; VCAM, vascular cell adhesion molecule; TNF, tumor necrosis factor; Tie-2, endothelial receptor tyrosine kinase; TARC, thymus and activation regulated chemokine; CCL, CC chemokine ligand; SAA, serum amyloid A; PlGF, placental growth factor; MIP, macrophage inflammatory protein; MDC, macrophage-derived chemokine; MCP, monocyte chemoattractant protein; IP-10, IFN-induced protein-10; CXCL, CX chemokine ligand; IL, interleukin; IL-1RA, interleukin-1 receptor antagonist; IFN, interferon; ICAM, intercellular adhesion molecule; Flt-1, Fms-related receptor tyrosine kinase-1; CRP, c-reactive protein; bFGF, basic fibroblast growth factor.
Figure 4
Figure 4
Mean changes in biomarker levels in TNFi initiators stratified by PASI50. Log-transformed mean changes from baseline to four-month follow-up stratified by PASI50 corresponding to 50% improvement in PASI included as a measure of cutaneous psoriasis (Table S4). * (star) represents changes that are statistically significant. TNFi, Tumor Necrosis Factor alpha inhibitor; PASI, Psoriasis Area Severity Index; VEGF, Vascular Endothelial Growth Factor; VCAM, vascular cell adhesion molecule; TNF, Tumor Necrosis Factor; Tie-2, endothelial receptor tyrosine kinase; TARC, Thymus and activation regulated chemokine; CCL, CC chemokine ligand; SAA, serum amyloid A; PlGF, Placental Growth Factor; MIP, macrophage inflammatory protein; MDC, macrophage-derived chemokine; MCP, monocyte chemoattractant protein; IP-10, IFN-induced protein-10; CXCL, CX chemokine ligand; IL, interleukin; IL-1RA, interleukin-1 receptor antagonist; IFN, interferon; ICAM, intercellular adhesion molecule; Flt-1, Fms-related receptor tyrosine kinase-1; CRP, c-reactive protein; bFGF, basic fibroblast growth factor.
Figure 5
Figure 5
Mean changes in biomarker level in IL-17Ai initiators stratified by PASI50. Log-transformed mean changes from baseline to four-month follow-up stratified by PASI50 corresponding to 50% improvement in PASI included as a measure of cutaneous psoriasis (Table S5). * (star) represents changes that are statistically significant. IL-17i, interleukin-17 inhibitor; PASI, Psoriasis Area Severity Index; VEGF, Vascular Endothelial Growth Factor; VCAM, vascular cell adhesion molecule; TNF, Tumor Necrosis Factor; Tie-2, endothelial receptor tyrosine kinase; TARC, Thymus and activation regulated chemokine; CCL, CC chemokine ligand; SAA, serum amyloid A; PlGF, Placental Growth Factor; MIP, macrophage inflammatory protein; MDC, macrophage-derived chemokine; MCP, monocyte chemoattractant protein; IP-10, IFN-induced protein-10; CXCL, CX chemokine ligand; IL, interleukin; IL-1RA, interleukin-1 receptor antagonist; IFN, interferon; ICAM, intercellular adhesion molecule; Flt-1, Fms-related receptor tyrosine kinase-1; CRP, c-reactive protein; bFGF, basic fibroblast growth factor.
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