Association of brain functional magnetic resonance activity with response to tumor necrosis factor inhibition in rheumatoid arthritis
Juergen Rech
University of Erlangen–Nuremberg, Erlangen, Germany
Drs. Rech and Hess contributed equally to this work.
Search for more papers by this authorAndreas Hess
University of Erlangen–Nuremberg, Erlangen, Germany
Drs. Rech and Hess contributed equally to this work.
Search for more papers by this authorStephanie Finzel
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorSilke Kreitz
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorMarina Sergeeva
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorMatthias Englbrecht
University of Erlangen–Nuremberg, Erlangen, Germany
Dr. Englbrecht has received speaking fees from Pfizer, Abbott, and MSD (less than $10,000 each).
Search for more papers by this authorArnd Doerfler
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorCorresponding Author
Georg Schett
University of Erlangen–Nuremberg, Erlangen, Germany
Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen–Nuremberg, Krankenhausstrasse 12, Erlangen D-91054, GermanySearch for more papers by this authorJuergen Rech
University of Erlangen–Nuremberg, Erlangen, Germany
Drs. Rech and Hess contributed equally to this work.
Search for more papers by this authorAndreas Hess
University of Erlangen–Nuremberg, Erlangen, Germany
Drs. Rech and Hess contributed equally to this work.
Search for more papers by this authorStephanie Finzel
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorSilke Kreitz
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorMarina Sergeeva
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorMatthias Englbrecht
University of Erlangen–Nuremberg, Erlangen, Germany
Dr. Englbrecht has received speaking fees from Pfizer, Abbott, and MSD (less than $10,000 each).
Search for more papers by this authorArnd Doerfler
University of Erlangen–Nuremberg, Erlangen, Germany
Search for more papers by this authorCorresponding Author
Georg Schett
University of Erlangen–Nuremberg, Erlangen, Germany
Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen–Nuremberg, Krankenhausstrasse 12, Erlangen D-91054, GermanySearch for more papers by this authorAbstract
Objective
To test whether brain activity predicts the response to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). Since clinical and laboratory parameters have proven unsuccessful in predicting response, we followed a radically different concept, hypothesizing that response to TNFi depends on central nervous system activity rather than the clinical signs of disease.
Methods
Sequential testing by functional magnetic resonance imaging (MRI) of the brain, anatomic MRI of the hand, and clinical assessment of arthritis were carried out in 10 patients with active RA before and 3, 7, and 28 days after the start of TNFi treatment.
Results
Baseline demographic and disease-specific parameters were identical in TNFi responders and nonresponders. The mean ± SEM decrease in the Disease Activity Score in 28 joints after 28 days was −1.8 ± 0.3 in TNFi responders (n = 5) and −0.2 ± 0.1 in nonresponders (n = 5). Responders showed significantly higher baseline activation in thalamic, limbic, and associative areas of the brain than nonresponders. Moreover, brain activity decreased within 3 days after TNFi exposure in the responders, preceding clinical responses (day 7) and responses observed on the anatomic hand MRI (day 28).
Conclusion
These data suggest that response to TNFi depends on brain activity in RA patients, reflecting the subjective perception of disease.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| ART_37761_sm_SupplFigure1.tif2 MB | Supplementary Figure 1. Graph theoretical analysis. A and B, Connectivity networks related to pain (compression paradigm) in patients with rheumatoid arthritis (RA) that responded to tumor necrosis factor inhibitors (TNFi) (A) and patients with RA that did not respond to TNFi (B) before (t0) and 3 days after treatment with certolizumab. Nodes represent brain structures, and edges represent the connectivity based on blood oxygen level---dependent time course correlation between brain structures. The size of the node indicates the node's degree; isolated nodes (with a degree of 0) were removed. Node positions indicate the anatomic centroids of the brain structures derived from a horizontal projection. Node colors represent different functional groups of brain structures. The thickness of each vertex indicates the connection strength (i.e., the correlation value). Arrows indicate brain structures that showed consistent differences in connectivity between responders and nonresponders. (Green arrows indicate the thalamus; red arrows indicate the posterior cingulate cortex; blue arrows indicate the insular cortex; gray arrows indicate the periaqueductal gray matter.) C, Brain structures analyzed for connectivity networks. CONTRA = contralateral; IPSI = ipsilateral; MPFC = medial prefrontal cortex; LPFC = lateral prefrontal cortex; AINS = anterior insular cortex; PINS = posterior insular cortex; MOT = motor cortex; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex; S1 = primary somatosensory cortex; S2 = secondary somatosensory cortex; TH = thalamus; PAR = parietal cortex; PAG = periaqueductal gray matter; CB = cerebellum. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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