Rheumatoid arthritis is a chronic autoimmune inflammatory disease that fundamentally affects the joints and that ends up causing joint destruction and leads to disability and reduced life expectancy if not treated properly. Current drug treatment is usually started after the diagnosis of rheumatoid arthritis, based on clinical symptoms and signs, mainly hand-predominant joint pain and inflammation and the presence of anti-citrullinated protein antibodies, which are proteins that have undergone changes (known as ACPAs). Yet before the first symptoms appear, the disease begins silently (preclinical phase), with the activation of the immune system’s T cells and B cells that will produce ACPA antibodies.
No therapeutic strategies have been developed that take aim at this previously asymptomatic phase of the disease until now. T cells are known to play a key role in the pathogenesis of rheumatoid arthritis, which is why a clinical trial was conducted to determine whether inhibiting these cells early, before clinical signs of inflammation appear, affects the development of the disease.
The results are promising, since treatment with the T cell inhibitor (Abatacept, which has been indicated for patients diagnosed with rheumatoid arthritis for years) seems to halt the development of the disease in a significant percentage of those affected. Specifically, 26% fewer cases of rheumatoid arthritis were diagnosed in people treated with Abatacept in the clinical trial carried out. Moreover, after six months of treatment, over half the patients who received the drug (28 of 49 participants) showed a major improvement in joint inflammation assessed by magnetic resonance imaging (MRI).
Another result to highlight is that after one year of the therapeutic intervention (i.e., the administration of the drug), its beneficial effects persisted, with less inflammation in the joints, clinical symptoms and risk of developing arthritis.
“These results indicate that if we could establish therapeutic interventions in the previous phase of the disease, there could be a window of opportunity to prevent rheumatoid arthritis from developing”, explains Juan D. Cañete. “We believe that this approach could help many people at risk of suffering from the disease”.
The clinical trial included 98 people (71% women, average age of 50 years) without a clinical diagnosis of rheumatoid arthritis, but who presented signs of suffering from the disease (pain without clinical signs of inflammation, but with detection of inflammation in the joints, bones or tendons via MRI). Half the participants were given Abatacept and the other half were given a placebo every week for six months, followed by a 12-month observational period.
Reference article
Rech, J., Tascilar, K., Hagen, M., Kleyer, A., Manger, B., Schoenau, V., Hueber, A. J., Kleinert, S., Baraliakos, X., Braun, J., Kiltz, U., Fleck, M., Rubbert-Roth, A., Kofler, D. M., Behrens, F., Feuchtenberger, M., Zaenker, M., Voll, R., Venhoff, N., … Schett, G. (2024). “Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): a randomised, international, multicentre, double-blind, placebo-controlled trial” in The Lancet. Elsevier BV. https://doi.org/10.1016/s0140-6736(23)02650-8
