Abatacept Reverses Subclinical Arthritis in Patients with High-risk to Develop Rheumatoid Arthritis -results from the Randomized, Placebo-controlled ARIAA Study in RA-at Risk Patients

Juergen Rech¹, Mikkel Ostergaard², Koray Tascilar³, Melanie Hagen⁴, Larissa Valor Mendez⁴, Arnd Kleyer⁴, Gerhard Kroenke⁴, David Simon⁵, Verena Schoenau⁴, Axel Hueber⁶, Stefan Kleinert⁷, Xenofon Baraliakos⁸, Martin Fleck⁹, Andrea Rubbert-Roth¹⁰, Frank Behrens¹¹, David Kofler¹², Martin Feuchtenberger¹³, Michael Zaenker¹⁴, Reinhard Voll¹⁵, Cornelia Glaser¹⁶, Eugen Feist¹⁷, Gerd Burmester¹⁸, Kirsten Karberg¹⁹, Johannes Strunk²⁰, Juan D Cañete²¹, Esperanza Naredo²², Maria Filkova²³, Ladislav Senolt²⁴ and Georg Schett²⁵, ¹Friedrich-Alexander University (FAU) Erlangen-Nuernberg and Universitaetsklinikum Erlangen, Department of Internal Medicine 3 - Rheumatology and Immunology, Germany, Erlangen, Germany, ²Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Glostrup, Denmark, ³Friedrich Alexander University of Erlangen Nuremberg, Universitaetsklinikum Erlangen Department of Medicine-3 Rheumatology and Immunology, Erlangen, Germany, ⁴Friedrich-Alexander University (FAU) Erlangen-Nuernberg and Universitaetsklinikum Erlangen, Medical Department 3, Rheumatology & Immunology, Erlangen, Germany, ⁵Department of Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nrnberg, Erlangen, Germany, ⁶sozialstiftung-bamberg.de, Bamberg, Germany, ⁷Praxisgemeinschaft Rheumatologie - Nephrologie (PGRN), Erlangen, Germany, ⁸Rheumazentrum Ruhrgebiet, Herne, Germany, ⁹Asklepios Klinikum Bad Abbach Klinik und Poliklinik für Rheumatologie/ Klin. Immunologie, Bad Abbach, Germany, ¹⁰Kantonspital St Gallen, St.Gallen, Switzerland, ¹¹Rheumatology & Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Fraunhofer Cluster Immune-Mediated Diseases (CIMD), Fraunhofer Cluster Immune-Mediated Diseases (CIMD), Frankfurt/Main, Germany, ¹²Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine; University Hospital Cologne, Cologne, Germany, ¹³MED | BAYERN OST GmbH Fachbereich Rheumatologie, Burghausen, Germany, ¹⁴Immanuel Klinikum Bernau Herzzentrum Brandenburg, Bernau, Germany, ¹⁵Department of Rheumatology and Clinical Immunology, University Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany, ¹⁶Universitätsklinikum Freiburg Klinik für Rheumatologie und Klinische Immunologie, Freiburg, Germany, ¹⁷Helios Department of Rheumatology, Vogelsang-Gommern, Germany, ¹⁸Charité University Medicine Berlin, Berlin, Germany, ¹⁹Praxis für Rheumatologie und Innere Medizin, Berlin, Germany, ²⁰Krankenhaus Porz am Rhein GmbH Rheumaklinik, Köln (Porz), Germany, ²¹Rheumatology Department, Hospital Clinic, Barcelona, Spain, ²²Department of Rheumatology and Joint and Bone Research Unit, Hospital Fundación Jiménez Díaz and Autónoma University, Madrid, Spain, ²³Institute of Rheumatology and Connective Tissue Research Laboratory, Department of Rheumatology of First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, ²⁴Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, ²⁵Universitätsklinikum Erlangen, Department of Internal Medicine 3 – Rheumatology and Immunology, Erlangen, Germany, Erlangen, Germany

Meeting: ACR Convergence 2021

Keywords: Anti-CCP, autoimmune diseases, Biomarkers, clinical trial, rheumatoid arthritis

Session Information

Date: Saturday, November 6, 2021

Title: Plenary I (0453–0457)

Session Type: Plenary Session

Session Time: 11:15AM-11:30AM

Background/Purpose: Rheumatoid arthritis (RA) has a preclinical phase that is characterized by the presence of antibodies against citrullinated proteins (ACPA), subclinical arthritis and pain. ACPA emerge years before the clinical onset of RA. In a subset of such individuals with ACPA (but not yet RA) imaging studies have revealed the presence of inflammatory and structural lesions. This subset of patients is at increased risk for the development of RA. As T cell mediated B cell activation is a key step for triggering the onset of autoimmune inflammatory diseases, such as RA, interventions that target this process may be useful for very early interventions, ultimately preventing the onset of RA. Abatacept appears to be an attractive approach in such task, as it interrupts the activation of T cells and has a well-known favourable safety profile in the treatment of RA.

To test whether abatacept, compared to placebo, reverses subclinical arthritis in patients with ACPA and MRI signs of inflammation, who have not yet developed RA.

Methods: ARIAA is a randomized double-blinded placebo-controlled multi-center study in RA-at risk individuals that ACPA positive and show MRI signs of inflammation. The study is composed by a 6 months treatment phase with either abatacept s.c. 125 mg weekly or placebo and 12 months follow up with no treatment. The primary analysis is done on the ITT population and missing values were rated as treatment failures. The primary endpoint was defined as an improvement in at least one of the MRI inflammation parameters (any change from baseline > 0 assessing synovitis, tenosynovitis and osteitis) according to the RAMRIS score.

Results: Between November 2014 and December 2019 a total of 139 patients were included into ARIAA by 14 study sites (11 in Germany, 1 in the Czech Republic and 2 in Spain). Of them, 100 patients were randomized to receive either abatacept or placebo. Two patients were excluded from the ITT population. As a result, 98 patients could be evaluated for efficacy and safety. The primary endpoint of ARIAA was reached: 61% of the patients in the abatacept group improved in at least one of the MRI parameters (synovitis, tenosynovitis, and osteitis) compared to only 31% in the placebo group (p=0.0043). Moreover, arthritis developed in 17 patients in the placebo group (34.7%) but only 4 patients (8.2%) in the abatacept group (p= 0.0025).
12 serious adverse events (1 gastritis, 1 cellulitis, 1 pneumonia, 1 tendinitis calcificans, 1 Rotator cuff syndrome, 1 Cholelithiasis, 1 x peripheral arterial occlusive disease, 1 x chronic idiopathic pain syndrom, 1 prostate cancer, 1 penile neoplasm; 1 trabeculectomy, 1 cataract operation) have been reported between 2014 – 2021, with only one (pneumonia) was assessed to have a causal relationship to study treatment.

Conclusion: These data show that abatacept significantly improves subclinical arthritis in patients at high risk to develop RA. In addition, the data also support the concept that early intervention may prevent or at least delay the development of RA.

Disclosures: J. Rech, Novartis, 2, 5, 6, SOBI, 2, 5, 6, AbbVie, 2, 6, Biogen, 2, 6, BMS, 2, 6, Chugai, 2, 6, GSK, 2, 6, Janssen, 2, 6, Lilly, 2, 6, MSD, 2, 6, Mylan, 2, 6, Roche, 2, 6, Sanofi, 2, 6, UCB, 2, 6; M. Ostergaard, AbbVie, 2, 5, 6, Bristol-Myers Squibb, 2, 6, Celgene, 2, 6, Novartis, 2, 5, 6, Boehringer Ingelheim, 2, 6, Eli Lilly, 2, 6, Hospira, 2, 6, Janssen, 2, 6, Merck, 2, 5, 6, Novo, 2, 6, Orion, 2, 6, Pfizer Inc, 2, 6, Regeneron, 2, 6, Roche, 2, 6, UCB, 2, 6, GSK, 2, 6, Mundipharma, 2, 6, Schering-Plough, 2, 6, Takeda, 2, 6, Wyeth, 2, 6, Centocor, 2, 5, 6; K. Tascilar, None; M. Hagen, None; L. Valor Mendez, None; A. Kleyer, None; G. Kroenke, None; D. Simon, None; V. Schoenau, None; A. Hueber, None; S. Kleinert, Novartis, 5, Abbvie, 1, Siemens Healthineers, 1, Sanofi, 11; X. Baraliakos, None; M. Fleck, None; A. Rubbert-Roth, AbbVie, 2, 6, Bristol-Myers Squibb, 2, 6, Chugai, 2, 6, Roche, 2, 6, Gilead, 2, 6, Janssen, 2, 6, Eli Lilly, 2, 6, Sanofi, 2, 6, Amgen, 2, 6, Novartis, 2, 6; F. Behrens, Chugai, 5, 6, AbbVie, 6, Amgen, 6, GlaxoSmithKline, 5, Janssen, 5, 6, Pfizer, 5, 6, Roche, 5, 6, Boehringer Ingelheim, 6, Celgene, 6, Eli Lilly, 6, Merck, 6, Novartis, 6, Sanofi, 6, UCB, 6; D. Kofler, None; M. Feuchtenberger, None; M. Zaenker, None; R. Voll, None; C. Glaser, None; E. Feist, R-Pharm, 2, 6, Abbvie, 2, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, AB2Bio, 6, BMS, 6, Celgene, 6, Janssen, 6, Eli Lilly, 2, 5, 6, Medac, 6, MSD, 6, Roche/Chugai, 2, 5, 6, Sanofi, 6, Sobi, 6, UCB, 6; G. Burmester, AbbVie, 2, 5, 6, Eli Lilly, 2, 5, 6, MSD, 2, 5, 6, Pfizer, 2, 5, 6, Roche, 2, 5, 6, Sanofi, 2, 5, 6, UCB, 2, 5, 6, Galapagos, BV, 2, 6, Gilead Sciences, Inc., 2, 6; K. Karberg, None; J. Strunk, None; J. Cañete, Abbvie, 6, Pfizer, 6, Janssen, 6; E. Naredo, AbbVie, 6, Roche, 6, BMS, 6, Pfizer, 6, UCB, 6, Lilly, 5, 6, Novartis, 6, Janssen, 6, Celgene GmbH, 6; M. Filkova, None; L. Senolt, None; G. Schett, Janssen, 6, Novartis, 6, AbbVie, 6, Bristol Myers Squibb, 6, Celgene, 6, Eli Lilly, 6, UCB, 6, Roche, 6.

To cite this abstract in AMA style:

Rech J, Ostergaard M, Tascilar K, Hagen M, Valor Mendez L, Kleyer A, Kroenke G, Simon D, Schoenau V, Hueber A, Kleinert S, Baraliakos X, Fleck M, Rubbert-Roth A, Behrens F, Kofler D, Feuchtenberger M, Zaenker M, Voll R, Glaser C, Feist E, Burmester G, Karberg K, Strunk J, Cañete J, Naredo E, Filkova M, Senolt L, Schett G. Abatacept Reverses Subclinical Arthritis in Patients with High-risk to Develop Rheumatoid Arthritis -results from the Randomized, Placebo-controlled ARIAA Study in RA-at Risk Patients [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/abatacept-reverses-subclinical-arthritis-in-patients-with-high-risk-to-develop-rheumatoid-arthritis-results-from-the-randomized-placebo-controlled-ariaa-study-in-ra-at-risk-patients/. Accessed .

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