Brain fMRI Predicts Responses to Certolizumab Pegol in RA. an International, Multi-center, Randomized, Double-blind, Placebo-controlled Trial (PreCePRA)

Juergen Rech¹, Hannah Schenker², Koray Tascilar¹, Melanie Hagen², Arnd Kleyer¹, David Simon¹, Larissa Valor Mendez², Verena Schoenau³, Jutta Prade⁴, Marina Sergeeva⁴, Mageshvar Sulvakumar⁵, Sandra Strobelt⁴, Laura Konerth⁴, Frank Behrens⁶, Christoph Baerwald⁷, Stephanie Finzel⁸, Reinhard Voll⁹, Axel Hueber¹⁰, Julie Roesch¹¹, Eugen Feist¹², José A. P. da Silva¹³, Arnd Doerfler¹¹, Nemanja Damjanov¹⁴, Andreas Hess¹⁵ and Georg Schett¹⁶, ¹Department of Internal Medicine 3, Friedrich-Alexander University (FAU) Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Bayern, Germany, ²Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany, Erlangen, Germany, ³Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany, Erlangen, ⁴Institute for Experimental Pharmacology, Erlangen, Germany, ⁵Insitute for Experimental Pharmacology , Fau Erlangen-Nürnberg, Erlangen, Germany, ⁶CIRI/Rheumatology & Fraunhofer TMP, Goethe University, Frankfurt, Germany, ⁷Uniklinik Leipzig, Medizinische Klinik III - Bereich Rheumatologie, Leipzig, Germany, ⁸Universitätsklinikum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Freiburg, Germany, ⁹Universitätsklinikum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Freibrug, ¹⁰Section Rheumatology, Sozialstiftung Bamberg, Bamberg, Germany, ¹¹Abteilung für Neuroradiologie, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany, Erlangen, Germany, ¹²Department of Rheumatology, Helios Vogelsang-Gommern, Vogelsang-Gommern, Germany, ¹³9.Centro Hospitalar e Universitário Coimbra (Rheumatology Department), Coimbra, Portugal, Coimbra, Portugal, ¹⁴University of Belgrade Medical School, Belgrade, Serbia, ¹⁵Institute for Experimental Pharmacology, Erlangen, ¹⁶Friedrich-Alexander-Universität Erlangen- Nuremberg, Erlangen, Germany

Meeting: ACR Convergence 2020

Keywords: Biomarkers, Brain, clinical trial, immunology, rheumatoid arthritis

Session Information

Date: Monday, November 9, 2020

Title: RA – Diagnosis, Manifestations, & Outcomes Poster IV: Lifespan of a Disease

Session Type: Poster Session D

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

Background/Purpose: Personalization of RA treatment is not optimal due to lack of predictors. We previously demonstrated in RA patients that central nervous system (CNS) pain response to tender joint compression, measured by using functional MRI (fMRI) of the brain rapidly wanes after 24 hours of anti-TNF administration and that a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumab-pegol (CZP)1,2. We therefore hypothesized that the CNS pain response upon compression of a painful joint could predict subsequent anti-TNF treatment response.

Methods: Adult RA patients fulfilling the 2010 ACR/EULAR classification criteria with a DAS28 >3.2 under stable DMARD treatment for at least 3 months were eligible. Patients underwent fMRI scanning of the brain at screening for stratification by CNS pain response. Whole brain BOLD-signal-voxel-count of 700 units classifying between low and high, and were randomized to CZP or placebo (2:1) The primary outcome was low disease activity (LDA, DAS28 ≤3.2) after 12 weeks of treatment.

Results: 156 RA patients, inadequate responders to csDMARD, signed the informed consent. 139 patients (46/47, 46/49 and 42/43) (99 females, 71%) with moderate-high disease activity (mean (SD) DAS-28: 4.83 (1.03)) could be included respectively and completed the 12-week study treatment. Geometric mean (SD) numbers of baseline BOLD signal positive voxels were 559 (10), 81 (12) and 2498 (3) in the 3 arms respectively. The mean DAS28 (SD) scores after 12 weeks of study treatment were Placebo: 3.89 (1.29), CZP-L: 3.42 (1.06) and CZP-H: 3.06 (1.04). LDA was achieved in 12/47 patients (25.5 %) in placebo, 22/49 (44.9%) in the CZP-L, and 25/43, (58.1%) in the CZP-H arm. The linear effect term for the ordinal study group variable supported a linear trend of increasing CZP treatment effect with increasing baseline CNS pain response. RR (95% CI) for achieving LDA with each unit increase in treatment category over placebo was 1.79 (1.24 to 2.74, p=0.003).

Conclusion: A higher pre-treatment brain activity in response to pain measured with fMRI predicts the chance of achieving low disease activity with CZP treatment.

Disclosure: J. Rech, Abbie, Biogen, BMS, Chugai, Celgene, EliLilly, Gilead, GSK, Janssen, MSD, Novartis, Roche, Sanofi, Sobi, UCB, 5, 8; H. Schenker, None; K. Tascilar, None; M. Hagen, None; A. Kleyer, Lilly, 8, Novartis, 8, BMS, 8, Sanofi, 8, Gilead, 8; D. Simon, Novartis, 8, Lilly, 5, 8, Janssen, 8, AbbVie, 5; L. Valor Mendez, None; V. Schoenau, None; J. Prade, None; M. Sergeeva, None; M. Sulvakumar, None; S. Strobelt, None; L. Konerth, None; F. Behrens, AbbVie, 2, 5, 8, Pfizer, 2, 5, 8, Roche, 2, 5, 8, Chugai, 2, 5, 8, Janssen, 2, 5, 8, Novartis, 2, 5, 8, UCB, 5, 8, BMS, 5, 8, Celgene, 5, 8, MSD, 5, 8, Biotest, 5, 8, Sanofi, 5, 8, Genzyme, 5, 8, Lilly, 5, 8, Boehringer, 5, 8, Galapagos, 5, 8; C. Baerwald, None; S. Finzel, None; R. Voll, None; A. Hueber, None; J. Roesch, None; E. Feist, AbbVie, 5, 8, BMS, 5, 8, Lilly, 5, 8, MSD, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, Roche, 5, 8, Sanofi, 5, 8, Sobi, 5, 8; J. da Silva, MyFibromyalgia®, a webcompany delivering services to patients with Fibromyalgia, 9; A. Doerfler, None; N. Damjanov, AbbVie, 5, 8, Pfizer, 5, 8, Roche, 5, 8, Richter Gedeon, 5, 8, MSD, 5, 8, Novartis, 5, 8; A. Hess, None; G. Schett, None.

To cite this abstract in AMA style:

Rech J, Schenker H, Tascilar K, Hagen M, Kleyer A, Simon D, Valor Mendez L, Schoenau V, Prade J, Sergeeva M, Sulvakumar M, Strobelt S, Konerth L, Behrens F, Baerwald C, Finzel S, Voll R, Hueber A, Roesch J, Feist E, da Silva J, Doerfler A, Damjanov N, Hess A, Schett G. Brain fMRI Predicts Responses to Certolizumab Pegol in RA. an International, Multi-center, Randomized, Double-blind, Placebo-controlled Trial (PreCePRA) [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/brain-fmri-predicts-responses-to-certolizumab-pegol-in-ra-an-international-multi-center-randomized-double-blind-placebo-controlled-trial-precepra/. Accessed .

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