Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
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.
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.   Active RA patients failing csDMARDs with a DAS28-ESR>3.2 and at least three tender and/or swollen joints received a brain BOLD (blood-oxygen-level dependent) fMRI scan upon joint compression at screening. Patients were then randomized into a 12-week double-blinded treatment phase with 200mg Certolizumab-Pegol every two weeks (arm 1: fMRI BOLD signal >2000 voxel, i.e. 2 cm3; arm 2: fMRI BOLD signal <2000 voxel) or placebo (arm 3) or. 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.
In responders screening signal volume, i.e. sum of significantly coupled voxels after FDR thresholding, was higher compared to non-responders 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.
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): p. 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): p. 3731-6.
To cite this abstract in AMA style:Schenker H, Hess A, Konerth L, Sergeeva M, Prade J, Kleyer A, Reiser M, Hueber AJ, Englbrecht M, Feist E, Voll R, Bannert B, Baerwald C, Rösch J, Dörfler A, da Silva JAP, Damjanov N, Schett G, Rech J. Prediction of Response to Certolizumab-Pegol in Rheumatoid Arthritis By Functional MRI of the Brain – an Interim Analysis of an Ongoing Investigator Initiated Phase III Trial [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/prediction-of-response-to-certolizumab-pegol-in-rheumatoid-arthritis-by-functional-mri-of-the-brain-an-interim-analysis-of-an-ongoing-investigator-initiated-phase-iii-trial/. Accessed June 26, 2019.
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