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P026 Baseline autoantibody profile in rheumatoid arthritis associates with early treatment response but not long-term outcomes
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  1. EC de Moel1,
  2. VF Derksen1,
  3. LA Trouw1,
  4. H Bang2,
  5. RJ Goekoop3,
  6. I Speyer4,
  7. TW Huizinga1,
  8. CF Allaart1,
  9. RE Toes1,
  10. D van der Woude1
  1. 1Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
  2. 2Orgentec Diagnostika, Mainz, Germany
  3. 3Rheumatology, Haga Hospital
  4. 4Rheumatology, Haaglanden Medical Centre, The Hague, Netherlands

Abstract

Introduction 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 clinically relevant and associates with treatment outcomes.

Objectives To investigate 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 sera of 399 seropositive RA patients in the IMPROVED study1 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 4 citrullinated and 2 acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on;

  • change in disease activity score (DAS)–44 between 0 and 4 months,

  • initial drug–free remission (DFR: drug–free DAS44<1.6) achieved between 1 and 2 years of follow–up, and

  • long–term sustained DFR until last follow–up.

Results Corrected for age, gender, smoking, BMI, and baseline Health Assessment Questionnaire score, patients with a broad autoantibody profile at baseline had a significantly better early treatment response: ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 isotypes: −1.5 [p<0.001], −1.7 [p=0.003], and −1.8 [p=0.001] vs −2.2. Similar results were observed for AMPA-number; ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 AMPAs, respectively: −1.7 [p=0.016], −1.5 [p<0.001], and −1.9 [p=0.22] vs −2.1. 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 results were observed.

Conclusions A broad baseline autoantibody profile is associated with a better early treatment response and a worse chance of achieving DFR at early stages, but not later in the treatment regimen, suggesting that the relevance of the autoantibody profile for treatment outcomes diminishes over time. 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.

Reference

  1. . Heimans. AR&T2016;18:23.

Disclosure of interest None declared

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