Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 15;210(2):141-150.
doi: 10.1093/cei/uxac085.

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  1 , Krista Kuuliala  2 , Anniina Virtanen  1 , Antti Kuuliala  2 , Maaria Palmroth  1 , Ritva Peltomaa  3 , Krista-Liisa Vidqvist  4 , Marjatta Leirisalo-Repo  2   3 , Olli Silvennoinen  1   5   6 , Pia Isomäki  1   4
Affiliations

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 et al. Clin Exp Immunol. .

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.

PubMed Disclaimer

Figures

Graphical Abstract
Graphical Abstract
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Firestein GS, McInnes IB.. Immunopathogenesis of rheumatoid arthritis. Immunity 2017, 46, 183–96. doi:10.1016/j.immuni.2017.02.006. - DOI - PMC - PubMed
    1. Schwartz DM, Bonelli M, Gadina M, O’Shea JJ.. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol 2016, 12, 25–36. doi:10.1038/nrrheum.2015.167. - DOI - PMC - PubMed
    1. Gadina M, Le MT, Schwartz DM, Silvennoinen O, Nakayamada S, Yamaoka K, et al. . Janus kinases to jakinibs: from basic insights to clinical practice. Rheumatology 2019, 58, i4–i16. doi:10.1093/rheumatology/key432. - DOI - PMC - PubMed
    1. Kuuliala K, Kuuliala A, Koivuniemi R, Oksanen S, Hämäläinen M, Moilanen E, et al. . Constitutive STAT3 phosphorylation in circulating CD4+ T lymphocytes associates with disease activity and treatment response in recent-onset rheumatoid arthritis. PLoS One 2015, 10, e0137385. doi:10.1371/journal.pone.0137385. - DOI - PMC - PubMed
    1. Isomäki P, Junttila I, Vidqvist KL, Korpela M, Silvennoinen O.. The activity of JAK-STAT pathways in rheumatoid arthritis: constitutive activation of STAT3 correlates with interleukin 6 levels. Rheumatology 2015, 54, 1103–13. - PubMed

Publication types