gms | German Medical Science

43. Kongress der Deutschen Gesellschaft für Rheumatologie, 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 25. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

02.-05. September 2015, Bremen

Canakinumab therapy responding genes in SJIA are INVERSELY disregulated in adult onset still's disease

Meeting Abstract

  • Eugen Feist - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Arndt-Holger Brachat - Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Frank Behrens - CIRI am Klinikum der Johann Wolfgang Goethe-Universität, Rheumatologie, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Frankfurt/Main
  • Norbert Blank - Universitätsklinikum Heidelberg, Medizinische Klinik V, Sektion Rheumatologie, Heidelberg
  • Nanguneri Nirmala - Novartis Institutes of Biomedical Research, Cambridge, Cambridge, United Kingdom
  • Christof Specker - Universitätsklinikum Essen, St. Josef Krankenhaus, Klinik für Rheumatologie und klinische Immunologie, Essen
  • Matthias Witt - Klinikum der Universität München, Medizinische Klinik und Poliklinik IV, Rheumaeinheit, München
  • Jan Zernicke - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Alberto Martini - Ospedale Gaslini Genova, Genova, Italy
  • Guido Junge - Novartis Pharma AG, Basel, Switzerland

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Bremen, 02.-05.09.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc50.06 - RA.06

doi: 10.3205/15dgrh029, urn:nbn:de:0183-15dgrh0297

Published: September 1, 2015

© 2015 Feist et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Introduction: Adult-onset Still’s disease (AOSD) is a rare auto-inflammatory disorder resembling a similar pediatric syndrome known as systemic juvenile idiopathic arthritis (SJIA).1 The superimposable systemic and clinical features in SJIA and AOSD suggest that both clinical phenotypes represent a disease continuum with a pediatric (SJIA) and more adult-onset (AOSD).2 Analyses of gene expression profiles may be useful not only for disease classification, diagnosis, and prognosis, but also to identify disease specific treatment effects that counteract the underlying pathological mechanisms. Here, we address the question: How do genes that respond to canakinumab treatment in SJIA patients3 behave in AOSD patients with active disease relative to healthy controls and prior to IL-1 targeting therapy?

The objective it to determine how genes that respond to IL-1β blockade with canakinumab in SJIA patients behave in AOSD patients relative to healthy controls.

Methods: SJIA gene expression profiles pre- and post canakinumab treatment were compared with AOSD patients relative to healthy subjects using Affymetrix U133Plus2 DNA microarrays.

Results: Consistently, all genes down-regulated in SJIA following canakinumab treatment were upregulated in a majority of AOSD patients with active disease relative to healthy subjects and prior to canakinumab treatment. A few of the AOSD patients resembled healthy subjects. Comparison of the gene expression patterns to neutrophil counts suggested that elevated neutrophil numbers were closely correlated to the upregulation of IL-1 associated gene expression.

Conclusion: Results are consistent with and further support the concept of a Still’s disease continuum that presents as pediatric/juvenile SJIA or adult-onset Still’s disease. Moreover, they suggest that AOSD is an IL-1 driven condition that is also mechanistically similar to SJIA and that the observed canakinumab response signature is likely to show a comparable treatment response to IL-1β blockade in AOSD.