Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes

Background: The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. Methods: In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on (1) change in disease activity score (DAS) 44 between 0 and 4 months, (2) initial drug-free remission (DFR, drug-free DAS44 < 1.6) achieved between 1 and 2 years of follow up, and (3) long-term sustained DFR until last follow up. Results: Patients with a broad autoantibody profile at baseline had a significantly better early treatment response: Delta DAS 0-4 months of 1-2, 3-4, and 5-6 vs 7-8 isotypes, -1.5 (p < 0.001), -1.7 (p = 0.03), and -1.8 (p = 0.04) vs -2.2. Similar results were observed for AMPA number. However, patients with a broad baseline autoantibody profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar trends were observed. Conclusions: A broad baseline autoantibody profile is associated with a better early treatment response. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity, which could make the underlying disease processes initially more suppressible by medication. The lack of association with long-term sustained DFR suggests that the relevance of the baseline autoantibody profile diminishes over time.