Longitudinal Change in the Central Nervous System Pain Response After Treatment with Certolizumab or Placebo. a Post-hoc Analysis from the Pre-CEPRA Trial

Juergen Rech¹, Hannah Schenker², Koray Tascilar¹, Melanie Hagen², Larissa Valor Mendez², Verena Schoenau³, Marina Sergeeva⁴, Jutta Prade⁴, Mageshvar Sulvakumar⁵, Laura Konert⁶, Arnd Kleyer¹, David Simon¹, Sandra Strobelt⁴, Frank Behrens⁷, Christoph Baerwald⁸, Stephanie Finzel⁹, Reinhard Voll¹⁰, Axel Hueber¹¹, Eugen Feist¹², Julie Roesch¹³, José A. P. da Silva¹⁴, Arnd Doerfler¹³, Nemanja Damjanov¹⁵, Andreas Hess¹⁶ and Georg Schett¹⁷, 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-Nuremberg, Erlangen, Germany, ⁶Institute for Experimental Pharmacology, FAU Erlangen-Nürnberg, Erlangen, ⁷CIRI/Rheumatology & Fraunhofer TMP, Goethe University, Frankfurt, Germany, ⁸Uniklinik Leipzig, Medizinische Klinik III - Bereich Rheumatologie, Leipzig, Germany, ⁹Universitätsklinikum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Freiburg, Germany, ¹⁰Universitätsklinikum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Freibrug, ¹¹Section Rheumatology, Sozialstiftung Bamberg, Bamberg, Germany, ¹²Department of Rheumatology, Helios Vogelsang-Gommern, Vogelsang-Gommern, Germany, ¹³Abteilung für Neuroradiologie, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany, Erlangen, Germany, ¹⁴9.Centro Hospitalar e Universitário Coimbra (Rheumatology Department), Coimbra, Portugal, Coimbra, Portugal, ¹⁵Belgrade University School of Medicine, Belgrade, Serbia, ¹⁶Institute for Experimental Pharmacology, Erlangen, ¹⁷Friedrich-Alexander-Universität Erlangen- Nuremberg, Erlangen, Germany

Meeting: ACR Convergence 2020

Keywords: autoimmune diseases, Biologicals, Biomarkers, Brain, immunology

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: Biologicals – bring a hope of recovery or amelioration to people suffering from RA, but only half of the patients respond to such treatment. Therefore, finding reliable biomarkers predicting response is very valuable. Previously we demonstrated that central nervous system (CNS) response to nociceptive stimuli, measured by fMRI of the brain, decreases already after 24 hours and that a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumab-pegol (CZP). 1,2 Therefore we hypothesized that the CNS response upon compression of a painful joint could predict subsequent anti-TNF treatment response.

To follow the longitudinal effect of CZP treatment on brain activity in RA patients stratified byhigh and low brain activation volumes measured by BOLD fMRI at baseline and to compare their brain activity during 24 weeks of treatment to that of placebo in DMARD-refractory RA patients.

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 the first fMRI at screening for stratification. Whole brain BOLD-signal-voxel-count of 700 classifying between low and high and patients were randomized to CZP or placebo (2:1 ratio) resulting in 3 study arms (CZP low voxel count (CZP-L), CZP high voxel count (CZP-H), and placebo). The second fMRI was performed after 12 and the third fMRI – after 24 weeks. In parallel control stimulation we measured brain activation during non-painful finger tapping.

Results: 156 patients, inadequate responders to csDMARD signed the informed consent. In the finger tapping control paradigm, fMRI showed no significant changes in the number of brain-wide activated voxels in CZP-L and CZP-H arms, but, surprisingly, there was a significant decrease (p=0.043) in the placebo arm in fMRI-3 compared to the pre-treatment fMRI-1 value. By painful stimulation in CZP-L fMRI showed significant increase in the number of brain-wide activated voxels (p=0.043) in fMRI-2 as compared to fMRI-1 with no further significant changes. Most importantly, in CZP-H the number of activated voxels was significantly reduced (p=0.037) in fMRI-2 and continued to decrease further in fMRI-3 ( p=0.007).

Conclusion: As revealed by our study high pre-treatment fMRI BOLD brain activity in response to pain seems to serve as a (long-term) positive predictor of patient’s response to 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; L. Valor Mendez, None; V. Schoenau, None; M. Sergeeva, None; J. Prade, None; M. Sulvakumar, None; L. Konert, None; A. Kleyer, Lilly, 8, Novartis, 8, BMS, 8, Sanofi, 8, Gilead, 8; D. Simon, Novartis, 8, Lilly, 5, 8, Janssen, 8, AbbVie, 5; S. Strobelt, 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; 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. Roesch, None; J. da Silva, MyFibromyalgia®, a webcompany delivering services to patients with Fibromyalgia, 9; A. Doerfler, None; N. Damjanov, None; A. Hess, None; G. Schett, None.

To cite this abstract in AMA style:

Rech J, Schenker H, Tascilar K, Hagen M, Valor Mendez L, Schoenau V, Sergeeva M, Prade J, Sulvakumar M, Konert L, Kleyer A, Simon D, Strobelt S, Behrens F, Baerwald C, Finzel S, Voll R, Hueber A, Feist E, Roesch J, da Silva J, Doerfler A, Damjanov N, Hess A, Schett G. Longitudinal Change in the Central Nervous System Pain Response After Treatment with Certolizumab or Placebo. a Post-hoc Analysis from the Pre-CEPRA Trial [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/longitudinal-change-in-the-central-nervous-system-pain-response-after-treatment-with-certolizumab-or-placebo-a-post-hoc-analysis-from-the-pre-cepra-trial/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/longitudinal-change-in-the-central-nervous-system-pain-response-after-treatment-with-certolizumab-or-placebo-a-post-hoc-analysis-from-the-pre-cepra-trial/