Mechanistic studies of IL-17 versus TNF blockade in Spondyloarthritis (SpA)

Concept

Both TNF and IL-17A are pivotal pathogenic cytokines in SpA. In this project, we hypothesize that blockade of IL-17A and TNF affects different pathophysiological pathways.

Facts and figures

Project lead
N Yeremenko
AMC Amsterdam
n. g.yeremenko@amsterdamumc.nl
FOREUM research grant: € 300.000
2016–2019

Meet the team

Project Lead

N Yeremenko
AMC Amsterdam
C Miceli
Institute Pasteur Paris
L Rogge
Institute Pasteur Paris
C van der Laken
VU Medisch Centrum
L Salij
Stichting Bechterew in Beweging
G van der Zalm
Stichting Bechterew in Beweging
D Simon
University Hospital

Objectives

We aim to identify specific biological effects by systematic translational comparison of IL-17A versus TNF blockade in SpA patients using combined molecular, cellular and imaging approaches with the overall goal to establish a path towards stratified medicine.

Goals/Milestones

  • Kick-off meeting in March 2017
  • First-patient-in in the 4 key studies (tissue immunopathology, cytokine profiles, PET-CT, micro-CT)
  • Last-patient-out in the 4 key studies
  • Analysis of the individual data sets
  • Integration of the different data sets
  • Completion of the publications and reports

Publications

  • Menegatti S, Bianchi E, Rogge L. Anti-TNF Therapy in Spondyloarthritis and Related Diseases, Impact on the Immune System and Prediction of Treatment Responses. Frontiers in Immunology, Front. Immunol., 19 March 2019 | https://doi.org/10.3389/fimmu.2019.00382
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  • Eleni Kampylafka, Isabelle d’Oliveira, Christina Linz, Veronika Lerchen, Fabian Stemmler, David Simon, Matthias Englbrecht, Michael Sticherling, Jürgen Rech, Arnd Kleyer, Georg Schett, Axel J. Hueber. Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study. Arthritis Res Ther. 2018 Jul 27;20(1):153. doi: 10.1186/s13075-018-1653-5
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  • Menegatti S, Guillemot V, Latis E, Yahia-Cherbal H, Mittermüller D, Rouilly V, Mascia E, Rosine N, Koturan S, Millot G, Leloup C, Duffy D, Gleizes A, Hacein-Bey-Abina S; Milieu Intérieur Consortium, Sellam J, Berenbaum F, Miceli C, Dougados M, Bianchi E, Rogge L. Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo. Ann Rheum Dis. 2020 Dec 2:annrheumdis-2020-218304. doi: 10.1136/annrheumdis-2020-218304. Online ahead of print.PMID: 33268443
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  • Fiechter R.H., de Jong H. M, van Mens L. J.J., Fluri I.A., Tas S. W., Baeten D. L. P., Yeremenko N. G., van de Sande M. G. H. IL-12p40/IL-23p40 Blockade With Ustekinumab Decreases the Synovial Inflammatory Infiltrate Through Modulation of Multiple Signaling Pathways Including MAPK-ERK and Wnt. Front Immunol 4 March 2021. doi: 10.3389/fimmu.2021.611656
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  • N. Yeremenko. Out of the shadow of IL-17A: the role of Il-17F and other IL-17 family cytokines in spondyloarthritis. Current Opinion in Rheumatology

Patient voice

A lay advisory board of patients will be instrumental in the interpretation of the data, in particular in addressing the question if and how the anticipated biologic profiles can be applied in a useful way to stratify individual patients or patient groups to aTNF versus aIL-17A treatment.

Project Map