Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response

Atte Valli, Krista Kuuliala, Anniina Virtanen, Antti Kuuliala, Maaria Palmroth, Ritva Peltomaa, Krista-Liisa Vidqvist, Marjatta Leirisalo-Repo, Olli Silvennoinen, Pia Isomäki

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Abstract

The data on the effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analyzed how tofacitinib treatment and thus inhibition of the Janus kinase-signal transducer and activation of transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, 16 patients with active RA [28-joint disease activity score (DAS28) >3.2] despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) started tofacitinib treatment 5 mg twice daily. Levels of 92 inflammation-related plasma proteins were determined by proximity extension assay at baseline and at 3 months. Tofacitinib treatment for 3 months, in csDMARD background, decreased the mean DAS28 from 4.4 to 2.6 (P < 0.001). Marked (>20%) and statistically significant (P < 0.05) changes were found in the levels of 21 proteins, 18 of which decreased and 3 increased. Of these proteins, 17 are directly involved in inflammatory responses or in the cellular response to cytokines. The highest (>50%) decrease was observed for interleukin-6 (IL-6), C-X-C motif chemokine ligand 1, matrix metalloproteinase-1, and AXIN1. Higher baseline levels of IL-6 and lower levels of C-C motif chemokine 11 and Delta and Notch-like epidermal growth factor-related receptors were associated with DAS28 improvement. Our results indicate that tofacitinib downregulates several proinflammatory plasma proteins that may contribute to the clinical efficacy of tofacitinib. In addition, soluble biomarkers may predict the treatment response to tofacitinib.

Original languageEnglish
Pages (from-to)141-150
Number of pages10
JournalClinical and Experimental Immunology
Volume210
Issue number2
DOIs
Publication statusPublished - 15 Dec 2022
Publication typeA1 Journal article-refereed

Keywords

  • Humans
  • Antirheumatic Agents/therapeutic use
  • Arthritis, Rheumatoid/drug therapy
  • Biomarkers
  • Blood Proteins
  • Chemokines
  • Inflammation
  • Interleukin-6
  • Protein Kinase Inhibitors/therapeutic use
  • Pyrroles/therapeutic use
  • Treatment Outcome

Publication forum classification

  • Publication forum level 1

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