Artikel
Combination of clinical parameters and biomarkers for the prediction of colchicine dose increase in patients with Familial Mediterranean Fever
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Autoren
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Anne-Marie Knieper
- Charité - Universitätsmedizin Berlin, Klinik für Pädiatrie mit Schwerpunkt Pneumologie und Immunologie, Berlin
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Jens Klotsche
- Deutsches Rheuma-Forschungszentrum (DRFZ), Programmbereich Epidemiologie, Berlin
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Elke Lainka
- Universitätsklinikum Essen Kinderrheumatologie, Essen
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Annette Friederike Jansson
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Ludwig-Maximilians-Universität, München
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Tim Niehues
- HELIOS Kliniken Krefeld, Krefeld
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Ulrich Neudorf
- Universitätsklinikum Essen Kinderrheumatologie, Essen
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Prasad Thomas Oommen
- Universitätsklinikum Düsseldorf, Zentrum für Kinder- und Jugendmedizin, Klinik für Kinder-Onkologie, Hämatologie und klinische Immunologie, Düsseldorf
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Rainer Berendes
- Kinderkrankenhaus St. Marien, Landshut
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Frank Dressler
- Medizinische Hochschule Hannover, Pädiatrische Pneumologie, Allergologie & Neonatologie, Hannover
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Thomas Berger
- Vestische Kinder- und Jugendklinik der Universität Witten/Herdecke, Pädiatrische Rheumatologie, Datteln
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Christoph Rietschel
- Clementine Hospital Frankfurt, Kinderklinik, Frankfurt/Main
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Dirk Foell
- Department of Paediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster
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Helmut Wittkowski
- Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Klinik für Pädiatrische Rheumatologie und Immunologie, Münster
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Tilmann Kallinich
- Charité - Universitätsmedizin Berlin, Klinik für Pädiatrie mit Schwerpunkt Pneumologie und Immunologie, Sektion Rheumatologie, Berlin
| Veröffentlicht: | 4. September 2017 |
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Gliederung
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Background: Colchicine is the standard therapy for prophylaxis of attacks and amyloid deposition in patients with FMF. The aim of this study was to identify clinical parameters and biomarkers, which predict a colchicine dose increase in patients with FMF in the near future; therefore we analyzed, whether a single parameter (attack frequency and/or various biomarkers) or combinations of them predicted an upcoming dose increment in already treated patients.
Methods: Data from 409 pediatric FMF patients (4566 visits, mean of 3.2 visits/year per patient) with a mean period of follow-up of 63 months derived from the national AID-registry were statistical analysed with SPSS. The AID-Register collects data on patients with autoinflammatory syndromes. Serum levels of S100-molecules were determined by ELISA.
Results: Persistent attacks as well as elevated CRP, SAA, S100A12 or S100A8/9 levels increased - as solely analyzed parameter - the likelihood for a dose increase with a factor of 1.62 to 1.94. Combining two parameters led to a better predictive value, especially when attack frequency and S100A12 or S100A8/9 were analyzed (OR of 3.38 and 3.29). When analyzing combinations of three parameters, it becames obvious that combining SAA and CRP did not lead to a significant increase in the predictive value. In case four or five parameters were increased the OR for a dose increase ranged between 4.26 and 4.66. When analysing only patients with homozygous M694V mutations even higher associations were observed. Especially the inclusion of the biomarker S100A12 increased the OR for a dose increase in the upcoming 12 months up to 7.27.
Conclusion: Colchicine therapy is currently mainly guided by the occurrence of clinical symptoms and serological inflammation. The additional analysis of S100 as sensitive biomarkers help to identify patients at risk for dose increases, especially in patients with a high risk of severe disease. Furthermore, this data suggests that a combined analysis of SAA and CRP does not increase the accuracy of a dose increase prediction.
