Artikel
Prediction of Response to Certolizumab-Pegol in Rheumatoid Arthritis (PreCePRA) by functional MRI of the Brain – an Interim Analysis of an ongoing Investigator initiated Phase III Trial
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Autoren
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Hannah Schenker
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Andreas Hess
- Friedrich-Alexander Universität Erlangen, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Emil-Fischer-Zentrum, Erlangen
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Laura Konerth
- Friedrich-Alexander Universität Erlangen, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Emil-Fischer-Zentrum, Erlangen
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Marina Sergeeva
- Friedrich-Alexander Universität Erlangen-Nürnberg, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Emil-Fischer-Zentrum, Erlangen
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Jutta Prade
- Friedrich-Alexander Universität Erlangen-Nürnberg, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Erlangen
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Arnd Kleyer
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Michaela Reiser
- Universität Erlangen-Nürnberg Medizinische Klinik 3, Rheumatologie & Immunologie, Erlangen
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Axel Hueber
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Matthias Englbrecht
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Eugen Feist
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Reinhard Voll
- Department of Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg
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Bettina Bannert
- Department of Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg
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Christoph G. O. Baerwald
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
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Julie Rösch
- Friedrich-Alexander Universität Erlangen-Nürnberg, Institut für Neuroradiologie, Erlangen
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Arnd Dörfler
- Friedrich-Alexander Universität Erlangen-Nürnberg, Institut für Neuroradiologie, Erlangen
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Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Jürgen Rech
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
| Veröffentlicht: | 4. September 2017 |
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Gliederung
Text
Background: Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as one third of patients do not respond adequately to TNFi. We investigated whether brain activity associated to arthritis measured by functional magnetic resonance imaging (fMRI) can function as a predictor of response to TNFi in RA patients.
Methods: This is an interim analysis of the first 50 patients of the PreCePRA trial, a multi-center, randomized, double-blind, placebo-controlled fMRI trial on patients with RA [1], [2]. Active RA patients failing csDMARDs with a DAS28-ESR>3.2 and at least three tender and/or swollen joints received a BOLD (blood-oxygen-level dependent) brain fMRI scan upon joint compression at screening. Patients were then randomized into a 12-week double-blinded treatment phase with placebo (arm 1) or 200mg Certolizumab-Pegol every two weeks (arm 2: fMRI BOLD signal >2000 voxel, i.e. 2 cm3; arm 3: fMRI BOLD signal <2000 voxel). DAS28-ESR low disease activity at 12 weeks was assigned as primary endpoint. A 12-week follow-up phase in which patients were switched from the placebo to the treatment arm followed the blinded phase. fMRI was carried out at screening as well as after 12 and 24 weeks of receiving Certolizumab-Pegol or placebo.
Results: In 31 patients (responders) screening signal volume, i.e. sum of significantly coupled voxels after FDR thresholding, was significantly higher compared to 19 patients (non-responders) (p<0.001) allowing discrimination between the two groups prior to treatment. In responders we detected a persistent decrease of BOLD volume at week 12 and 24 compared to screening (r2=0.561) whereas BOLD volume in non-responders persistently increased (r2=0.589).
Conclusion: Based on this interim analysis we conclude that high BOLD volumes in fMRI indicating high-level brain representation of pain in arthritis predict response to TNFi. These data represent the first encouraging results of the PreCePRA brain fMRI study supporting the concept that increased RA-related brain activity correlates with response to TNFi.
References
- 1.
- Rech J, et al. Association of brain functional magnetic resonance activity with response to tumor necrosis factor inhibition in rheumatoid arthritis. Arthritis Rheum. 2013;65(2): 325-33.
- 2.
- Hess A, et al. Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A. 2011;108(9):3731-6.
