Background Seropositive and seronegative rheumatoid arthritis (RA) are distinct disease entities with regard to pathophysiological mechanisms and disease outcomes. However, over the past years it has become clear that the autoantibody profile of seropositive RA is very diverse, involving multiple post-translational modifications and isotypes, and it seems unlikely that a single autoantibody will be informative for identifying groups at risk of poor treatment response. Instead of individual autoantibodies, we hypothesized that the breadth of seropositive patients' profile may be the best reflection of the underlying immunopathology, and would be able to identify homogenous treatment response and inform treatment decisions.
Objectives To investigate whether baseline autoantibody profile is associated with treatment response and the ability to taper off medication in RA patients.
Methods All RA patients fulfilling the 2010 ACR/EULAR Criteria included in the IMPROVED study1 that were seropositive for routine clinical testing for anti-cyclic citrullinated peptide-2 (anti-CCP2 IgG), rheumatoid factor (RF IgM), or our in-house assay for anti-carbamylated protein antibodies (anti-CarP IgG) were selected (n=381). In baseline sera of these patients, we measured IgG, IgM, and IgA isotypes for each family (except IgG for RF) and reactivity against 4 citrullinated peptides (cit-vimentin 59–74, cit-fibrinogen β 36–52 and α 27–43, and cit-enolase 5–20). We investigated associations between autoantibody profile and 1) change in disease activity score (DAS)-44 over time and 2) sustained drug-free remission, defined as the ability to taper off medication and remain in remission for ≥1 year after achieving DAS44<1.6.
Results The initial treatment response (mean ΔDAS 0–4 months) in seropositive patients with a broad autoantibody profile (7–8 isotypes present) was better than in those with fewer isotypes present (ΔDAS 0–4 months of 7–8 isotypes vs 1–2, 3–4, and 5–6 isotypes, respectively: -2.2 vs -1.5 [p<0.001], -1.7 [p=0.04], and -1.8 [p=0.04]). In contrast, the presence of multiple autoantibodies was unfavorable regarding the long-term outcome of sustained drug-free remission. Within seropositive disease, patients with more isotypes and more reactivities to citrullinated peptides significantly less often achieved sustained drug-free remission (SDFR) (Figure).
Conclusions Seropositive patients with a broader autoantibody profile at baseline initially react better to treatment, but are not able to taper off medication and remain in remission. This may be relevant in individualized decision-making for tapering medication, as these results suggest that disease with a broad autoantibody response, as proxy for an active humoral autoimmunity, is more difficult to control in the long-term without sustained therapy.
Heimans, AR&T 2016, 18:23.
Disclosure of Interest None declared