TOPLINE:

By 10 years, 12.8% of patients initially diagnosed with seronegative rheumatoid arthritis (RA) received a different diagnosis — most often spondyloarthritis — and 26.6% achieved drug-free remission. About one fifth started a biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

METHODOLOGY:

• Researchers conducted a retrospective, population-based cohort study to assess long-term outcomes in patients with seronegative RA.
• They included 176 adults with incident seronegative RA (mean age, 56.3 years; 68% women) from a county in Minnesota between 2005 and 2014. All patients had negative results for rheumatoid factor and anti-cyclic citrullinated peptide antibodies before inclusion in the study.
• Researchers evaluated changes in diagnosis confirmed at two or more rheumatology visits, drug-free remission (defined as at least 6 months off all RA therapy with no synovitis on clinical examination), and initiation of biologics and JAK inhibitors.
• The 10-year cumulative incidences were estimated after accounting for competing risks over a median duration of 11.8 years.

TAKEAWAY:

• By 10 years, 12.8% of patients experienced a change in diagnosis, most commonly to spondyloarthritis (cumulative incidence rate, 4.0%). Only 2% of all patients developed autoantibody-positive RA.
• Drug-free remission was achieved in 26.6% of patients by 10 years; most patients maintained remission for at least 12 months (median duration, 6.3 years).
• By 10 years, 19.9% of patients started a biologic or targeted synthetic DMARD.
• Older age was associated with a reduced risk for diagnosis change, but the association was of borderline statistical significance. No other characteristics were significant predictors of diagnosis change or drug-free remission.

IN PRACTICE:

“Although a change in diagnosis was relatively uncommon compared to other outcomes assessed, ongoing investigation to improve accuracy in initial diagnosis of seronegative inflammatory arthritis is important, which may include specific areas such as advanced imaging, synovial pathology, novel autoantibodies, and integration of artificial intelligence,” the authors of the study wrote.

SOURCE:

This study was led by Bradly A. Kimbrough, MD, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. It was published online on December 12, 2025, in Arthritis Care & Research.

LIMITATIONS:

This retrospective study had no standardized DMARD tapering; some patients in long-term remission may not have discontinued DMARDs, likely underestimating drug-free remission. Drug-free remission was assessed by clinical exam rather than by validated disease activity scores. The median follow-up duration of 11.8 years may have led to missing of outcomes occurring later.

DISCLOSURES:

This study received support from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and National Institute on Aging. Additional support came from the Mayo Clinic Research Committee, fees paid by the users of Rochester Epidemiology Project, and the National Center for Advancing Translational Sciences. Several authors disclosed receiving institutional payments, having pending patents and licensing or royalty relationships, and serving on advisory councils or professional committees of certain organizations, including the American College of Rheumatology.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.