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.
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 10). 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 December 8, 2021.
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