In Barcelona's Hospital Clínic, researchers have discovered a way to stop an autoimmune disease in its tracks—preventing arthritis from developing in four out of five patients who would otherwise have fallen ill. Over two years, a team led by Raimon Sanmartí at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) tested abatacept, a drug that silences overactive immune cells, against the standard treatment hydroxychloroquine in 70 patients with palindromic rheumatism—a painful condition that strikes without warning and, for roughly half of those who have it, becomes something far worse.
Palindromic rheumatism announces itself through sudden flare-ups: joint inflammation that swells acutely then subsides, only to return days or weeks later. The real danger is that around half of patients eventually cross a threshold into rheumatoid arthritis, a chronic condition that causes irreversible damage to the joints and profoundly disrupts daily life. This progression is most likely in people carrying specific autoantibodies—proteins that their own immune system mistakenly produces to attack their joints—making early intervention crucial.
The clinical trial, conducted across 14 Spanish hospitals and published in Nature Medicine, yielded striking results. Only 20 percent of patients treated with abatacept developed arthritis, compared with 50 percent receiving hydroxychloroquine. Beyond preventing progression, patients on abatacept experienced something more immediate: their palindromic symptoms improved dramatically. "Patients treated with abatacept are more likely to achieve complete remission of attacks associated with acute pain and joint swelling, and their inflammatory episodes are less severe," explains Isabel Haro, head of the Peptide Synthesis and Biomedical Applications Unit at the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC).
For decades, doctors have treated palindromic rheumatism with hydroxychloroquine—an anti-inflammatory that dampens symptoms but does little to stop the underlying progression. Without clinical evidence to guide them toward better options, they had few alternatives. This trial changes that calculus. Both drugs proved safe and well tolerated throughout the two-year period, meaning the choice is now between a treatment that manages symptoms and one that can actually alter the disease's course.
The significance extends beyond the numbers. Rheumatoid arthritis imposes an enormous burden on patients' quality of life and on health systems worldwide. Preventing its development in a substantial portion of cases represents what researchers call a "paradigm shift"—moving from treating active disease to intervening early, when the window to prevent chronic damage remains open. "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," Sanmartí says. Abatacept works by inhibiting lymphocytes, a type of white blood cell that wrongly identifies the joints as a threat and attacks them, stopping that cascade before it becomes established.
The research involved several national centers, including analysis of how different biomarkers evolve during treatment. Though abatacept and hydroxychloroquine produced similar changes in autoantibody levels, the difference in clinical outcomes underscores how important timing is in managing autoimmune disease. Catching patients at the palindromic stage—before irreversible arthritis sets in—and offering them a drug that can achieve remission rather than merely manage flare-ups represents a meaningful step forward in how rheumatic diseases are approached.