Anne-Marie Knieper1, Jens Klotsche2,3, Elke Lainka4, Thomas Berger5, Frank Dressler6, Annette F Jansson7, Christoph Rietschel8, Prasad T Oommen9, Rainer Berendes10, Tim Niehues11, Ulrich Neudorf4, Dirk Foell12, Helmut Wittkowski12, Tilmann Kallinich1,13. 1. Pediatric Pneumology and Immunology, Charité University Medicine Berlin. 2. German Rheumatism Research Centre Berlin, Leibniz Institute. 3. Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medicine Berlin, Berlin. 4. Pediatric Rheumatology, Department of Paediatrics, University of Duisburg-Essen, Essen. 5. Pediatric Neurology, Vestische Kinderklinik Datteln, Datteln. 6. Centre for Paediatrics and Adolescent Medicine, Hannover Medical School, Hannover. 7. Department of Rheumatology and Immunology, Hauner Children's Hospital, Ludwig Maximilians University, Munich. 8. Clementine Kinderhospital, Verein Frankfurter Stiftungskrankenhäuser, Frankfurt. 9. Department of Pediatric Oncology, Hematology and Clinical Immunology, Center of Child and Adolescent Health, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf. 10. Pediatric Rheumatology, Children's Hospital St Marien, Landshut. 11. Zentrum für Kinder- und Jugendmedizin, HELIOS Klinikum Krefeld, Krefeld. 12. Department of Paediatric Rheumatology and Immunology, University of Münster, Münster. 13. Social Pediatric Center, Charité University Medicine Berlin, Berlin, Germany.
Abstract
Objectives: The aim was to analyse factors influencing the individual colchicine dose in children with FMF, to evaluate the impact of dose adjustment on the clinical course and inflammation and to identify clinical parameters and biomarkers that predict dose increase in the near future. Methods: Data from 409 paediatric FMF patients (4566 visits) derived from the national auto-inflammatory diseases registry were analysed. Serum concentrations of S100 molecules were determined by ELISA. Results: The age-dependent colchicine dose is influenced by the present genotype. The body surface area is the anthropometric parameter that correlates best with the applied dosages. Colchicine introduction and dose increase lead to significant reduction of clinical symptoms and inflammation. During established colchicine therapy, an increase of one single biomarker increases the likelihood of a dose increment in the next 12 months with a factor of 1.62-1.94. A combination of biomarkers including S100 molecules increases this odds ratio up to 4.66 when analysing all patients and up to 7.27 when analysing patients with a high risk of severe disease. Conclusion: Colchicine therapy is currently guided mainly by the occurrence of clinical symptoms and serological inflammation. Other factors, such as the genotype, the body surface area and biomarkers, will help to manage colchicine therapy in a more individualized fashion. The additional analysis of S100 molecules as sensitive biomarkers will help to identify patients at risk for dose increases in the near future.
Objectives: The aim was to analyse factors influencing the individual colchicine dose in children with FMF, to evaluate the impact of dose adjustment on the clinical course and inflammation and to identify clinical parameters and biomarkers that predict dose increase in the near future. Methods: Data from 409 paediatric FMFpatients (4566 visits) derived from the national auto-inflammatory diseases registry were analysed. Serum concentrations of S100 molecules were determined by ELISA. Results: The age-dependent colchicine dose is influenced by the present genotype. The body surface area is the anthropometric parameter that correlates best with the applied dosages. Colchicine introduction and dose increase lead to significant reduction of clinical symptoms and inflammation. During established colchicine therapy, an increase of one single biomarker increases the likelihood of a dose increment in the next 12 months with a factor of 1.62-1.94. A combination of biomarkers including S100 molecules increases this odds ratio up to 4.66 when analysing all patients and up to 7.27 when analysing patients with a high risk of severe disease. Conclusion:Colchicine therapy is currently guided mainly by the occurrence of clinical symptoms and serological inflammation. Other factors, such as the genotype, the body surface area and biomarkers, will help to manage colchicine therapy in a more individualized fashion. The additional analysis of S100 molecules as sensitive biomarkers will help to identify patients at risk for dose increases in the near future.
Authors: Philip C Robinson; Robert Terkeltaub; Michael H Pillinger; Binita Shah; Vangelis Karalis; Eleni Karatza; David Liew; Massimo Imazio; Jan H Cornel; Peter L Thompson; Mark Nidorf Journal: Am J Med Date: 2021-08-18 Impact factor: 4.965
Authors: T Kallinich; N Blank; T Braun; E Feist; U Kiltz; U Neudorf; P T Oommen; C Weseloh; H Wittkowski; J Braun Journal: Z Rheumatol Date: 2019-02 Impact factor: 1.372
Authors: Susanne M Benseler; Jasmin B Kuemmerle-Deschner; Tatjana Welzel; Anna L Wildermuth; Norbert Deschner Journal: Pediatr Rheumatol Online J Date: 2021-09-14 Impact factor: 3.054