Anti-nuclear antibody development is associated with poor treatment response to biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis

Background: It has been well known that TNF-α inhibitor (TNFi) treatment for patients with rheumatoid arthritis (RA) is associated with anti-nuclear antibody (ANA) development. We previously reported that ANA development was associated with poor outcomes of infliximab (IFX) treatment (1). However, no replication studies have been reported to date. In addition, whether the findings are true to general biological disease-modifying anti-rheumatic drugs (bDMARDs) is uncertain. Methods: To evaluate an association between treatment response and ANA development during bDMARDs treatment in RA and to analyze correlates of ANA development, Japanese RA patients treated with (n = 657) or without (n = 211) bDMARDs as a first line bDMARD were enrolled from a single center cohort. ANA was measured by an indirect immunofluorescence assay at multiple time points of treatment. We analyzed associations between ANA development and insufficient response to treatment. Correlates of ANA development were also analyzed. Results: ANA development (≥2 times baseline levels) at 3 months and at 6–12 months after bDMARDs initiation were significantly associated with insufficient response at 3–12 months (odds ratio (OR)=3.51, p = 0.020) and at 12–24 months (OR = 3.16, p = 0.038), respectively. The associations remained significant after conditioning on the use of each bDMARD. The use of IFX (OR = 6.24, p < 0.001) was a risk for ANA development, and other TNFi showed the same tends as infliximab. On the other hand, non-TNFi bDMARDs were not associated with ANA development. Conclusions: ANA development could be a marker of poor treatment response in RA patients undergoing bDMARDs treatment. Undefined factors might influence ANA development and subsequent poor bDMARDs outcome in RA.