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Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study

BACKGROUND: Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as approximately half of the patients do not respond adequately to TNFi. Thus, an unmet need exists to better predict ther...

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Autores principales: Schenker, H.M., Tascilar, K., Konerth, L., Sergeeva, M., Prade, J., Strobelt, S., Kleyer, A., Simon, D., Mendez, L., Hagen, M., Schönau, V., Hueber, A., Roesch, J., Dörfler, A., Hess, A., Schett, G., Rech, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144682/
https://www.ncbi.nlm.nih.gov/pubmed/34041413
http://dx.doi.org/10.1016/j.conctc.2021.100770
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author Schenker, H.M.
Tascilar, K.
Konerth, L.
Sergeeva, M.
Prade, J.
Strobelt, S.
Kleyer, A.
Simon, D.
Mendez, L.
Hagen, M.
Schönau, V.
Hueber, A.
Roesch, J.
Dörfler, A.
Hess, A.
Schett, G.
Rech, J.
author_facet Schenker, H.M.
Tascilar, K.
Konerth, L.
Sergeeva, M.
Prade, J.
Strobelt, S.
Kleyer, A.
Simon, D.
Mendez, L.
Hagen, M.
Schönau, V.
Hueber, A.
Roesch, J.
Dörfler, A.
Hess, A.
Schett, G.
Rech, J.
author_sort Schenker, H.M.
collection PubMed
description BACKGROUND: Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as approximately half of the patients do not respond adequately to TNFi. Thus, an unmet need exists to better predict therapeutic outcome of biologicals. OBJECTIVES: We investigated whether brain activity associated with arthritis measured by functional magnetic resonance imaging (fMRI) of the brain can serve as a predictor of response to TNFi in RA patients. METHODS: PreCePRA is a multi-center, randomized, double-blind, placebo-controlled fMRI trial on patients with RA [1] [2]. Active RA patients failing csDMARDs therapy with a DAS28 > 3.2 and at least three tender and/or swollen joints underwent 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 200 mg Certolizumab Pegol (CZP) every two weeks (arm 1: fMRI BOLD signal activated volume > 2000 voxel, i.e. 2 cm(3); arm 2: fMRI BOLD signal activated volume <2000 voxel) or placebo (arm 3). DAS28 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 CZP or placebo. CONCLUSION: We hypothesize that high-level central nervous representation of pain in patients with rheumatoid arthritis predicts response to the TNFi CZP which we further investigate in the PreCePRA trial.
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spelling pubmed-81446822021-05-25 Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study Schenker, H.M. Tascilar, K. Konerth, L. Sergeeva, M. Prade, J. Strobelt, S. Kleyer, A. Simon, D. Mendez, L. Hagen, M. Schönau, V. Hueber, A. Roesch, J. Dörfler, A. Hess, A. Schett, G. Rech, J. Contemp Clin Trials Commun Article BACKGROUND: Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as approximately half of the patients do not respond adequately to TNFi. Thus, an unmet need exists to better predict therapeutic outcome of biologicals. OBJECTIVES: We investigated whether brain activity associated with arthritis measured by functional magnetic resonance imaging (fMRI) of the brain can serve as a predictor of response to TNFi in RA patients. METHODS: PreCePRA is a multi-center, randomized, double-blind, placebo-controlled fMRI trial on patients with RA [1] [2]. Active RA patients failing csDMARDs therapy with a DAS28 > 3.2 and at least three tender and/or swollen joints underwent 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 200 mg Certolizumab Pegol (CZP) every two weeks (arm 1: fMRI BOLD signal activated volume > 2000 voxel, i.e. 2 cm(3); arm 2: fMRI BOLD signal activated volume <2000 voxel) or placebo (arm 3). DAS28 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 CZP or placebo. CONCLUSION: We hypothesize that high-level central nervous representation of pain in patients with rheumatoid arthritis predicts response to the TNFi CZP which we further investigate in the PreCePRA trial. Elsevier 2021-05-04 /pmc/articles/PMC8144682/ /pubmed/34041413 http://dx.doi.org/10.1016/j.conctc.2021.100770 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Schenker, H.M.
Tascilar, K.
Konerth, L.
Sergeeva, M.
Prade, J.
Strobelt, S.
Kleyer, A.
Simon, D.
Mendez, L.
Hagen, M.
Schönau, V.
Hueber, A.
Roesch, J.
Dörfler, A.
Hess, A.
Schett, G.
Rech, J.
Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study
title Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study
title_full Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study
title_fullStr Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study
title_full_unstemmed Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study
title_short Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain – Study protocol for a randomized double-blind controlled study
title_sort prediction of response to certolizumab-pegol in rheumatoid arthritis (precepra) by functional mri of the brain – study protocol for a randomized double-blind controlled study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144682/
https://www.ncbi.nlm.nih.gov/pubmed/34041413
http://dx.doi.org/10.1016/j.conctc.2021.100770
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