Abatacept Reduced Arthritis Progression in Palindromic Rheumatism Trial

A clinical trial led by researchers from Hospital Clínic de Barcelona, the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) has compared the effectiveness of abatacept and hydroxychloroquine in preventing the development of rheumatoid arthritis in patients with palindromic rheumatism, an autoimmune disease that progresses to arthritis in approximately half of all patients. The trial was conducted over two years across 14 hospitals throughout Spain and involved 70 patients with palindromic rheumatism. The findings, published in Nature Medicine, indicate that abatacept is significantly more effective than hydroxychloroquine in preventing the onset of arthritis.

Palindromic rheumatism is characterised by intermittent episodes of joint inflammation, with acute flare-ups lasting a few days and resolving spontaneously. However, around half of patients eventually develop rheumatoid arthritis, a chronic disease that causes irreversible joint damage. This risk is particularly high in individuals with biomarkers such as rheumatoid factor and anti-citrullinated peptide antibodies. The presence of these two autoantibodies—proteins of the immune system that mistakenly attack the body’s own organs and tissues—is used in the diagnosis of the disease.

Until now, in the absence of clinical trial evidence, the standard approach has been to treat patients with palindromic rheumatism using hydroxychloroquine, a drug with anti-inflammatory and immunosuppressive properties aimed at improving disease symptoms. In this context, the team led by Raimon Sanmartí, head of the Inflammatory Arthropathies Research Group at IDIBAPS, conducted a two-year clinical trial involving 70 patients with palindromic rheumatism. The objective was to compare the effectiveness of hydroxychloroquine with abatacept, a lymphocyte inhibitor—a type of white blood cell that attacks the joints after mistakenly identifying them as a threat—in reducing progression from palindromic rheumatism to rheumatoid arthritis

The results show that treatment with abatacept significantly reduces progression to rheumatoid arthritis. Only 20% of patients receiving abatacept developed arthritis, compared with 50% of those treated with hydroxychloroquine. Furthermore, patients treated with abatacept not only avoided progression to rheumatoid arthritis in most cases, but also experienced a significant improvement in palindromic rheumatism symptoms. “The study shows that patients treated with abatacept are more likely to achieve complete remission of attacks associated with acute pain and joint swelling, and that their inflammatory episodes are less severe,” explains Isabel Haro, Head of the Peptide Synthesis and Biomedical Applications Unit at IQAC-CSIC. The research team also highlights that both drugs proved safe and well tolerated throughout the trial.

Early intervention

“The results of this study indicate that we can intervene at an early stage to modify the natural course of the disease and reduce the risk of patients developing more severe and irreversible conditions,” says Sanmartí. “This opens the door to a paradigm shift in the treatment of these patients.”

The study, which involved several national research centres, also analysed the evolution of a number of biomarkers (autoantibodies) developed by the CSIC research group during patient follow-up. “Although no significant differences were observed between abatacept and hydroxychloroquine in terms of autoantibody responses, this work demonstrates the value of immunomodulatory approaches in the early stages of disease, when it is still possible to prevent progression to more severe and chronic forms,” notes Haro.

Rheumatoid arthritis is a disease that significantly affects patients’ quality of life and places a considerable burden on healthcare systems. Preventing its development in a substantial proportion of cases represents an important advance in the management of rheumatic diseases.

Reference: Sanmarti R, Pérez-García C, de-Toro FJ, et al. Abatacept versus hydroxychloroquine for prevention of rheumatoid arthritis in individuals with palindromic rheumatism: a randomized open-label trial. Nat Med. 2026. doi:10.1038/s41591-026-04395-6

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