Long-Term Prevention of RA in high-risk individuals after a 6-Month Placebo-Controlled Intervention with Abatacept -The ARIAA Trial

Koray Tascilar¹, Mikkel Ostergaard², Verena Schoenau³, Uta Kiltz⁴, Xenofon Baraliakos⁴, David Kofler⁵, Martin Feuchtenberger⁶, Ulrike Steffen⁷, Mario Zaiss⁸, Michael Zaenker⁹, Reinhard Voll¹⁰, Cornelia. Glaser¹¹, Holger Bang¹², Eugen feist¹³, Gerd Burmester¹⁴, Kirsten Karberg¹⁵, Joachim Strunk¹⁶, Juan Cañete¹⁷, Esperanza Naredo¹⁸, Mária Filková¹⁹, Ladislav Šenolt¹⁹, Georg Schett²⁰ and Juergen Rech⁷, ¹Department of Medicine ³ - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany, ²Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, and Copenhagen Center for Arthritis Research, Center for Rheumatology, Rigshospitalet, Glostrup, Denmark, ³- Department of Medicine ³ - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany., Erlangen, Germany, ⁴Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Herne, Germany, ⁵University of Cologne, Cologne, Germany, ⁶MED | BAYERN OST GmbH, Fachbereich Rheumatologie, Burghausen, Germany, Burghausen, Bayern, Germany, ⁷Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Department of Internal Medicine ³ - Rheumatology and Immunology, Erlangen, Germany, Erlangen, Bayern, Germany, ⁸¹Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Department of Internal Medicine ³ - Rheumatology and Immunology, Erlangen, Germany, Erlangen, Bayern, Germany, ⁹Immanuel Klinikum Bernau , Herzzentrum Brandenburg, Abteilung Innere Medizin, Bernau, Germany, Berlin, Germany, ¹⁰University Medical Center Freiburg, Freiburg, Germany, ¹¹Department of Rheumatology and Clinical Immunology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Freiburg, Baden-Wurttemberg, Germany, ¹²Orgentec, Mainz, Germany, ¹³Helios Department of Rheumatology, Vogelsang-Gommern, Germany, ¹⁴Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, Germany, ¹⁵Praxis für Rheumatologie und Innere Medizin, Rheumatologie, Berlin, Germany, Berlin, Germany, ¹⁶Krankenhaus Porz am Rhein GmbH, Rheumaklinik, Köln (Porz), Germany, Köln-Porz, Germany, ¹⁷Rheumatology Department, Hospital Clínic and IDIBAPS, Barcelona, Spain, Barcelona, Spain, ¹⁸Department of Rheumatology and Joint and Bone Research Unit. Fundación Jiménez Díaz University Hospital and Health Research Institute FJD-UAM, Madrid, Spain, MADRID, Spain, ¹⁹Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic, ²⁰Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany, Erlangen, Germany

Meeting: ACR Convergence 2025

Keywords: Anti-ACPA, autoimmune diseases, Biologicals, clinical trial, Rheumatoid Factor

Session Information

Date: Tuesday, October 28, 2025

Title: (2265–2289) Rheumatoid Arthritis – Treatment Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: A 6-month intervention with abatacept in the ARIAA trial (EUDRA-CT 2014–000555–93) significantly retarded the development of RA compared to placebo in ACPA-positive individuals with joint pain and subclinical inflammation on hand MRI. This inhibitory effect peaked at the end of the 6-month treatment period and was still discernible after 1-year of follow-up without any intervention. The durability of the inhibitory effect on development of RA is not known.Objectives: To assess the durability of the inhibitory effect of abatacept to develop RA observed in the ARIAA trial.

Methods: The ARIAA trial recruited individuals with positive ACPA antibodies, joint pain and findings of synovitis, tenosynovitis or bone marrow edema on the MRI of the dominant hand. Subjectswere randomized to receive a 6-month course of abatacept 125 mg sc weekly or placebo and followed without any treatment for additional 12 months. Individuals who did not develop RA during the study period of December 2014 and June 2021 were contacted up to November 2024 to ascertain their latest status for RA diagnosis based on the discretion of their primary physician. We used survival analysis methods and calculated restricted mean survival time difference, net average RA-free time gained due to treatment over time to evaluate the durability of treatment effect and compared the characteristics of participants who developed RA during study to those who developed RA later and who never developed RA

Results: 98 individuals with a positive ACPA were randomized to abatacept (49) or placebo (49). At the end of treatment (6 months) and observation (18 months) periods, RA developed in 4 (8%) and 17 (35%) participants in the abatacept group as opposed to 17 (35%) and 28 (57%) participants in the placebo group resulting in 15.3 weeks (95%CI, 4.3 to 26.3) of RA-free time gain on average in the abatacept group compared to placebo by the end of the study. After the closure of the study, 17 participants in the abatacept group and 8 participants in the placebo group developed RA during a median follow-up duration of 5.3 years after randomization (IQR, 1.9 to 7.2 years) which cumulated to 34/49 (69%) in the abatacept group and 36/49 (73%) in the placebo group. During this period the RA-free survival gain in the Abatacept group persisted for up to 5 years (figure 1A) increasing to ~40 weeks (figure-1B). The first derivative (Figure-1C) of the RMST difference curve indicates that the inhibitory effect (a positive slope for RA-free time gain) of abatacept during the treatment-period is offset initially during the first year after treatment cessation but then persisted for up-to five years after randomization and waned afterwards resulting in an ultimate catch-up of the placebo arm. A descriptive comparison of participants who never developed RA indicate that these had a lower ESR, lower RF levels, lower pain scores and better functional status at baseline (Table-1).

Conclusion: Abatacept showed a delayed inhibitory effect against the development of RA lasting for up-to 5 years after the initial 6-month intervention. Systemic inflammation, autoimmunity, pain, and function could help improve risk stratification while selecting individuals at risk of RA for a preventive intervention

RF rheumatoid factor, ACPA anti-citrullinated protein antibodies, MRI magnetic resonance imaging, ESR erythrocyte sedimentation rate, CRP c-reactive protein, VAS visual analog scale, RAID, rheumatoid arthritis impact of disease questionnaire, SF-36 short form 36 items, PCS physical component summary

1 Median (Q1, Q3); n (%)

2 Kruskal-Wallis rank sum test; Pearson’s Chi-squared test

Disclosures: K. Tascilar: None; M. Ostergaard: AbbVie, 2, 5, 6, Amgen, 5, BMS, 2, 5, 6, Celgene, 2, 5, 6, Eli Lilly, 2, 5, 6, Galapagos, 2, 6, Gilead, 2, 6, Janssen, 2, 6, MEDAC, 6, Merck, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 6, Sandoz, 6, UCB, 2, 5, 6; V. Schoenau: AbbVie/Abbott, 1, 6, Chugai, 5, 6, Novartis, 1, 6, Roche, 5; U. Kiltz: AbbVie, 2, 5, Amgen, 2, 5, Biocad, 2, 5, Biogen, 2, 5, BMS, 2, 5, Chugai, 2, 5, Eli Lilly, 2, 5, Fresenius, 2, 5, Gilead, 2, 5, Grünenthal, 2, 5, GSK, 2, 5, Hexal, 2, 5, Janssen, 2, 5, MSD, 2, 5, Novartis, 2, 5, onkowissen.de, 2, 5, Pfizer, 2, 5, Roche, 2, 5, UCB, 2, 5, Viatris, 2, 5; X. Baraliakos: AbbVie, 2, 5, 6, 12, Paid Instructor, Advanz, 2, 6, 12, Paid instructor, Alexion, 2, 6, 12, Paid instructor, Alphasigma, 2, 6, 12, Paid instructor, Amgen, 2, 6, 12, Paid instructor, BMS, 2, 6, 12, Paid instructor, Celgene, 6, Celltrion, 2, 5, 6, 12, Paid instructor, Cesas, 2, 6, 12, Paid instructor, Chugai, 2, 6, Clarivate, 6, 12, Paid instructor, Galapagos, 2, 6, 12, Paid instructor, J&J, 2, 6, 12, Paid instructor, Janssen, 5, Lilly, 2, 6, 12, Paid instructor, Merck, 6, MoonLake, 2, 5, 6, 12, Paid instructor, MSD, 2, Novartis, 2, 5, 6, 12, Paid instructor, Peervoice, 2, 6, 12, Paid instructor, Pfizer, 2, 6, 12, Paid instructor, Roche, 2, 6, 12, Paid instructor, Sandoz, 2, 6, 12, Paid instructor, Springer, 2, 6, 12, Paid instructor, Stada, 2, 6, 12, Paid instructor, Takeda, 2, 6, 12, Paid instructor, UCB, 2, 6, 12, Paid instructor, Zuellig, 2, 6, 12, Paid instructor; D. Kofler: AbbVie, 1, UCB, 1; M. Feuchtenberger: None; U. Steffen: None; M. Zaiss: None; M. Zaenker: None; R. Voll: None; C. Glaser: None; H. Bang: Orgentec, 3; E. feist: AB2Bio, 6, AbbVie/Abbott, 6, Alfasigma, 6, AstraZeneca, 6, Biogen, 6, Bristol-Myers Squibb(BMS), 6, Celgene, 6, Eli Lilly, 6, Galapagos, 6, Hexal, 6, Janssen, 6, Medac, 6, Novartis, 6, Pfizer, 6, Roche/Chugai, 6, R-Pharm, JSC, 6, Sandoz, 6, Sanofi, 6, Sobi, 6, UCB, 6; G. Burmester: Celltrion, 6, Chugai, 6, Fresenius, 6, Gedeon Richter, 6, Sanofi, 6; K. Karberg: None; J. Strunk: None; J. Cañete: None; E. Naredo: None; M. Filková: None; L. Šenolt: None; G. Schett: Cabaletta, 6, Eli Lilly, 6, Janssen, 6, Kyverna, 6, Novartis, 6, UCB, 6; J. Rech: Novartis, Sobi, 1, 2, 5, 6.

To cite this abstract in AMA style:

Tascilar K, Ostergaard M, Schoenau V, Kiltz U, Baraliakos X, Kofler D, Feuchtenberger M, Steffen U, Zaiss M, Zaenker M, Voll R, Glaser C, Bang H, feist E, Burmester G, Karberg K, Strunk J, Cañete J, Naredo E, Filková M, Šenolt L, Schett G, Rech J. Long-Term Prevention of RA in high-risk individuals after a 6-Month Placebo-Controlled Intervention with Abatacept -The ARIAA Trial [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/long-term-prevention-of-ra-in-high-risk-individuals-after-a-6-month-placebo-controlled-intervention-with-abatacept-the-ariaa-trial/. Accessed .

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