Prognostic value of longitudinal antinuclear antibody dynamics in rheumatoid arthritis: a retrospective cohort study

Background: The prognostic value of longitudinal antinuclear antibody (ANA) dynamics in rheumatoid arthritis (RA) remains unclear. Objectives: To examine whether ANA development (titer rise/seroconversion) is associated with 12-month clinical remission and to develop a prediction model for DAS28-CRP remission. Methods: We retrospectively enrolled 688 adults with RA (2010 criteria) from 2016-2023. ANA was assessed at baseline and 6 months (± 2 months); development was defined as a ≥1-dilution increase or seroconversion (<1:80 to ≥1:80). The primary endpoint was DAS28-CRP remission at 12 months (<2.6); other endpoints were secondary/exploratory. We used propensity score matching where appropriate. Multivariable logistic regression identified predictors, with performance assessed by AUC and calibration. Subgroup analyses distinguished seroconversion from titer elevation, and were stratified by baseline RF/anti-CCP status. Sensitivity analyses used a higher positivity threshold (≥1:160). Results: Baseline ANA positivity was 63.7%, typically low titers (1:80, 1:160). Among 467 patients with serial ANA data, 94 (20.1%) exhibited ANA development, which was associated with significantly higher post-treatment disease activity and lower remission rates across multiple criteria (e.g., DAS28-CRP 43.8% vs 65.2%, p=0.004). In multivariable analysis, ANA development independently predicted non-remission (OR 0.472, p=0.010) together with baseline DAS28-CRP (OR 0.745, p=0.017). The prediction model achieved moderate discriminative ability, with an area under the curve (AUC) of 0.715 in the training cohort and 0.705 in the testing cohort, alongside acceptable calibration. Stratified analysis revealed that the negative prognostic value of ANA development was most pronounced in RF-negative patients (adjusted OR = 0.29, p=0.048). Intriguingly, baseline homogeneous ANA pattern was associated with higher remission rates (63.8% vs. 41.5% in pure speckled pattern, p<0.001). Sensitivity analysis using a ≥1:160 cutoff yielded distinct findings: high ANA titer was associated with a higher likelihood of remission (OR = 1.624, p=0.016). Conclusions: Rising ANA titers/seroconversion during therapy are associated with reduced probability of DAS28-CRP remission at 12 months. The prognostic impact is modulated by baseline RF status, ANA fluorescence patterns, and the titer cutoff used. Conversely, a high baseline ANA titer (≥1:160) itself may identify a subgroup with distinct characteristics. Incorporating ANA dynamics into routine monitoring may improve risk stratification and clinical decision-making in RA.