Disease-associated Central Nervous System Activation Predicts Good Clinical Response to Tumor Necrosis Factor Inhibition in Rheumatoid Arthritis Patients - "The PreCePRA Study"

Juergen Rech¹, Prof. Dr. Andreas Hess², Koray Tascilar¹, Dr. Hannah Schenker³, verena schönau¹, Marina Sergeeva², Jutta Prade², Silke Kreitz², Mageshva Sulvakumar², Laura Konerth², Sandra Strobelt², Matthias Englbrecht⁴, Prof. Dr. Dr. Axel Hueber⁵, Eugen Feist⁶, Prof. Dr. Mario Zaiss¹, Gerd Burmester⁷, Frank Behrens⁸, Dr. Michaela Koehm⁹, Prof. Dr. Christoph Baerwald¹⁰, Dr. Stephanie Finzel¹¹, Dr. Arnd Kleyer¹², Prof. Dr. Reinhard Voll¹¹, Dr. Julie Roesch¹³, Prof. Dr. Arnd Doerfler¹³, Prof. Dr. Nemanja Damjanov¹⁴, Prof. José António P. Da Silva¹⁵ and Georg Schett¹⁶, ¹Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, Deutsches Zentrum für Immuntherapie (DZI), Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany, Erlangen, Germany, ²Institute for Experimental Pharmacology FAU Erlangen-Nürnberg, Erlangen, Germany, ³Department of Internal Medicine 3 - Rheumatology and Immunology, Department of Internal Medicine 1 - Gastroenterology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, Deutsches Zentrum für Immuntherapie (DZI), Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany, Erlangen, Germany, ⁴Freelance Healthcare Data Scientist, Eckental, ⁵Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, + Rheumatologie, Klinik für Innere Medizin 5, Klinikum Nürnberg Nord, Prof.-Ernst-Nathan-Str. 1, 90419, Nürnberg, Deutschland, Erlangen, Germany, ⁶Department of Rheumatology, Helios Clinic Vogelsang-Gommern, cooperation partner of the Otto von Guericke University Magdeburg, Gommern, Germany, ⁷Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, Germany, ⁸University Hospital Goethe University Frankfurt and Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany, ⁹Goethe-University & Fraunhofer ITMP, Frankfurt, Germany, ¹⁰Medizinische Klinik III - Bereich Rheumatologie, Liebigstraße 20, 04103 Leipzig, Leipzig, Germany, ¹¹Universitätsklinikum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Hugstetterstraße 55, 79106 Freiburg, Freiburg, Germany, ¹²Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, Deutsches Zentrum für Immuntherapie (DZI), Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany; Charité - Universitätsmedizin Berlin Med. Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie Berlin, Erlangen, Germany, ¹³Department of Neuroradiology, Friedrich - Alexander - Universitaet Erlangen - Nuernberg and Universitaetsklinikum Erlangen , Erlangen , Germany, Erlangen, Germany, ¹⁴Belgrade University School of Medicine, Institute Institute of Rheumatology, Belgrade, Belgrade, Serbia, ¹⁵Head of Department Reumatologia. Hospitais da Universidade (SRHUC), Coimbra, Portugal, ¹⁶Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

Meeting: ACR Convergence 2024

Keywords: Biomarkers, Magnetic resonance imaging (MRI), rheumatoid arthritis, TNF-blocking Antibody

Session Information

Date: Saturday, November 16, 2024

Title: Abstracts: RA – Diagnosis, Manifestations, & Outcomes II: Bad Blood (Serologic and Imaging Biomarkers)

Session Type: Abstract Session

Session Time: 3:00PM-4:30PM

Background/Purpose: Rheumatoid arthritis (RA) is an chronic inflammatory disease that is frequently treated with tumor necrosis factor inhibitors (TNFi). Little is known about predictors of response to TNFi. As clinical response in RA is measured by composite scores that contain a substantial number of subjective patients-orientated domains (pain, global disease perception) we speculated that patients with high disease representation in the central nervous system (CNS) may respond better to TNFi than patients in whom the disease is less represented in the CNS.

Methods: Phase 3,international multicenter, double-blind, placebo-controlled, parallel-group study with active RA patients. All patients underwent a functional MRI (fMRI) scan of the CNS at baseline measuring central nervous system CNS activation (voxels) by joint compression. Patients were stratified according to fMRI (high voxel, HV; low voxel, LV) and randomized 2:1 into treatment with the TNFi certolizumab-pegol (CZP) or placebo (PLB). The primary efficacy analysis compared the percentages of patients reaching low disease activity (LDA) according to DAS28 (≤3.2) at week 12. In addition, exploratory multi-parametric MRI assessment of brain anatomy and function was performed and analyzed with machine-learning approaches.

Results: 148 RA patients were screened and 139 patients were randomized to the HV-CZP arm(N=49), the LV-CZP arm (N=43) or PLB arm(N=47)patients. LDA was achieved by28/49 (57%) in HV-CZP,19/43 (44%) in LV-CZP and12/47 (26%) in PLB group at week 12. Response in the HV-CZP group but not in the LV-CZP group were significantly (p< 0.002) different from PLB group. HV-CZP and LV-CZP responses differed from placebo in patient-oriented outcomes (pain, patients global) but were similar in objective measures (CRP, joint swelling).The multi-parametric MRI together with machine learning confirmed, that only fMRI voxel size was able to separate CZP and PLB with an accuracy of 95.2%

Conclusion: High disease-associated CNS activation,measured by fMRI,predicts good clinical response of RA patients to TNFi.

148 patients were screened in total, but 9 patients had to be excluded: 8 patients did not fulfill all inclusion
criteria and 1 patient was not able to perform fMRI. Finally 139 patients were randomized into 3 groups:
92 patients received Certolizumab-Pegol (CZP), and were allocated to 2 different groups, stratified by the
fMRI results at baseline: 49 patients were included in the high voxel count (HV-CZP)- group and 43 patients
were included in the low voxel count (LV-CZP)- group. 47 patients were assigned to the placebo control
(PLB) group.

3D surface visualization of activated volumes.

Disclosures: J. Rech: Novartis, 1, 2, 6, Sobi, 1, 2, 6, UCB, 1, 2, 6; P. Hess: None; K. Tascilar: None; D. Schenker: None; v. schönau: None; M. Sergeeva: None; J. Prade: None; S. Kreitz: None; M. Sulvakumar: None; L. Konerth: None; S. Strobelt: None; M. Englbrecht: AbbVie, 2, Sanofi, 6; P. Hueber: None; E. Feist: AbbVie, 2, 6, Galapagos, 2, 5, 6, Lilly, 2, 5, 6, Medac, 6, Novartis, 2, 6, Pfizer, 2, 5, 6, Roche, 2, 6, Sobi, 2, 6; P. Zaiss: None; G. Burmester: AbbVie, 2, Amgen, 2, BMS, 2, Galapagos, 2, Lilly, 2, MSD, 2, Pfizer, 2, Sanofi, 2; F. Behrens: AbbVie, 2, 6, Boehringer Ingelheim, 2, 6, Bristol Myers Squibb, 2, 6, Celgene, 2, 5, 6, Chugai, 2, 5, 6, Eli Lilly, 2, 6, Galapagos, 2, 6, Genzyme, 2, 6, Gilead, 2, 6, Janssen, 2, 5, 6, MSD, 2, 6, Novartis, 2, 6, Pfizer, 2, 5, 6, Roche, 2, 5, 6, Sanofi, 2, 6, UCB, 2, 6; D. Koehm: None; P. Baerwald: None; D. Finzel: None; D. Kleyer: None; P. Voll: None; D. Roesch: None; P. Doerfler: None; P. Damjanov: None; P. Da Silva: None; G. Schett: Bristol-Myers Squibb(BMS), 6, Cabaletta, 6, Janssen, 6, Kyverna Therapeutics, 6, Novartis, 6.

To cite this abstract in AMA style:

Rech J, Hess P, Tascilar K, Schenker D, schönau v, Sergeeva M, Prade J, Kreitz S, Sulvakumar M, Konerth L, Strobelt S, Englbrecht M, Hueber P, Feist E, Zaiss P, Burmester G, Behrens F, Koehm D, Baerwald P, Finzel D, Kleyer D, Voll P, Roesch D, Doerfler P, Damjanov P, Da Silva P, Schett G. Disease-associated Central Nervous System Activation Predicts Good Clinical Response to Tumor Necrosis Factor Inhibition in Rheumatoid Arthritis Patients – “The PreCePRA Study” [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/disease-associated-central-nervous-system-activation-predicts-good-clinical-response-to-tumor-necrosis-factor-inhibition-in-rheumatoid-arthritis-patients-the-precepra-study/. Accessed .

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