Abatacept versus hydroxychloroquine for prevention of rheumatoid arthritis in individuals with palindromic rheumatism: a randomized open-label trial

# Abatacept versus hydroxychloroquine for prevention of rheumatoid arthritis in individuals with palindromic rheumatism: a randomized open-label trial *Published: 2026 May 14* A substantial proportion of individuals with palindromic rheumatism develop rheumatoid arthritis (RA). This randomized, open-label, multicenter trial aimed to assess whether 2 years of treatment with abatacept (n = 34; 125 mg subcutaneous injections weekly during the first year and every 2 weeks during the second year) compared with oral hydroxychloroquine (n = 36; 5 mg kg-1 per day) could reduce the frequency of RA development in individuals with palindromic rheumatism positive for rheumatoid factor and/or anticitrullinated protein antibody. The primary outcome was the development of persistent arthritis that fulfilled the 2010 RA classification criteria of the American College of Rheumatology and the European Alliance of Associations for Rheumatology, as evaluated by the participant clinicians during the 24 months of follow-up. Secondary outcomes included the frequency, intensity and duration of joint attacks, the proportion of patients in remission and the frequency of adverse events. In the primary analysis, in the modified full analysis set with failure imputation, 7 (20.6%) of the 34 participants treated with abatacept and 18 (50.0%) of the 36 participants treated with hydroxychloroquine developed RA during the 24 months of follow-up (P = 0.010; risk difference 29.4%, 95% confidence interval 8.2 to 50.7), meeting the primary endpoint. Using the available-data-only approach, the corresponding figures were 3 (10.0%) of 30 individuals and 10 (35.7%) of 28 individuals, respectively (P = 0.019). Compared with participants treated with hydroxychloroquine, participants treated with abatacept had a significantly longer time to progression to RA (hazard ratio 0.27, 95% confidence interval 0.07 to 0.96; log-rank test P = 0.0299). Abatacept was also associated with a reduced intensity of joint attacks and a higher frequency of symptom remission; however, there were no differences in the frequency of attacks between the two study drugs. No relevant differences in the evolution of antimodified peptide and/or protein antibody titers were observed between the two treatment arms. Both drugs were well tolerated. In patients with seropositive palindromic rheumatism, compared with hydroxychloroquine, abatacept given for 2 years reduced the risk of progression to RA and improved symptoms. ClinicalTrials.gov identifier NCT03669367 and EudraCT no. 2017-004543-20. DOI: 10.1038/s41591-026-04395-6