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

Hannah Schenker¹, Andreas Hess², Laura Konerth², Marina Sergeeva², Jutta Prade², Arnd Kleyer¹, Michaela Reiser¹, Axel J. Hueber¹, Matthias Englbrecht¹, Eugen Feist³, Reinhard Voll⁴, Bettina Bannert⁴, C Baerwald⁵, Julie Rösch⁶, Arnd Dörfler⁷, José António P. da Silva⁸, Nemanja Damjanov⁹, Georg Schett¹ and Juergen Rech¹, ¹Department of Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ²Institute of Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany, ³Department of Rheumatology and Clinical Immunology, Charité, Berlin, Berlin, Germany, ⁴Clinic for Rheumatology and Clinical Immunology, Medical University of Freiburg, Germany, Freiburg, Germany, ⁵Department of Rheumatology, University of Leipzig, Germany, Leipzig, Germany, ⁶Department of Neuroradiology, University of Erlangen-Nuremberg, Germany, Erlangen, Germany, ⁷Department of Neuroradiology, University of Erlangen-Nuremberg, Germany, e, Germany, ⁸Rheumatology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, ⁹Institute of Rheumatology, Belgrade University School of Medicine, Belgrade, Serbia

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Biologics, FMRI, rheumatoid arthritis (RA) and tumor necrosis factor (TNF)

Session Information

Date: Tuesday, November 7, 2017

Title: Imaging of Rheumatic Diseases Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

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 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.

Results:

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.

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): 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.

Disclosure: H. Schenker, None; A. Hess, None; L. Konerth, None; M. Sergeeva, None; J. Prade, None; A. Kleyer, None; M. Reiser, None; A. J. Hueber, None; M. Englbrecht, None; E. Feist, None; R. Voll, None; B. Bannert, None; C. Baerwald, None; J. Rösch, None; A. Dörfler, None; J. A. P. da Silva, None; N. Damjanov, None; G. Schett, None; J. Rech, None.

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 .

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