Anti‐carbamylated fibrinogen autoantibodies of IgG and IgA isotypes contribute to a better prognostic stratification in very early rheumatoid arthritis: data from the French national ESPOIR cohort

OBJECTIVE: To investigate the prevalence and longitudinal evolution of anti-carbamylated fibrinogen antibodies (ACa-Fib) of IgG and IgA isotypes in early rheumatoid arthritis (RA), and determine whether these antibodies provide additional diagnostic and prognostic information beyond anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF). METHODS: ACa-Fib IgG and IgA were quantified by in-house ELISA at baseline (M0), 6 months (M6), and 24 months (M24) in 619 patients with available 2010 ACR/EULAR classification criteria, including 575 RA patients, from the French ESPOIR cohort. Clinical, biological, and radiographic data were collected. Multivariable models and appropriate statistical analyses were used to assess associations between ACa-Fib levels and disease activity, therapeutic response, smoking exposure, CRP concentrations, and structural progression. RESULTS: At baseline, ACa-Fib IgG and IgA were detected in 16.6% and 6.3% of anti-CCP-negative RA patients, respectively. Baseline ACa-Fib levels were not associated with therapeutic response or remission. Over 24 months, ACa-Fib IgG levels decreased whereas IgA levels remained stable. Higher ACa-Fib IgA levels were associated with longer smoking duration (p=0.003) and cumulative smoking exposure (p=0.016). Patients in the highest quartile of ACa-Fib IgG (≥20.29 AU) had an increased risk of rapid radiographic progression (global p=0.004). Despite its markedly lower prevalence, ACa-Fib IgA (≥3.07 AU) was also associated with structural progression (OR=1.9, 95% CI 1.1-3.4, p=0.031). CONCLUSION: The distinct longitudinal behaviour and prognostic associations of ACa-Fib IgG and IgA highlight a previously underappreciated component of the anti-CarP response and support their utility as complementary biomarkers for improved risk stratification in early RA.