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Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status
  1. Debbie M Boeters1,
  2. Leonie E Burgers1,
  3. René EM Toes1,
  4. Annette van der Helm-van Mil1,2
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Rheumatology, Erasmus University Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Debbie M Boeters, Rheumatology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands; D.M.Boeters{at}


Objectives Sustained disease-modifying antirheumatic drug (DMARD)-free status, the sustained absence of synovitis after cessation of DMARD therapy, is infrequent in autoantibody-positive rheumatoid arthritis (RA), but approximates cure (ie, disappearance of signs and symptoms). It was recently suggested that immunological remission, defined as disappearance of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), underlies this outcome. Therefore, this long-term observational study determined if autoantibodies disappear in RA patients who achieved sustained DMARD-free remission.

Methods We studied 95 ACPA-positive and/or RF-positive RA patients who achieved DMARD-free remission after median 4.8 years and kept this status for the remaining follow-up (median 4.2 years). Additionally, 21 autoantibody-positive RA patients with a late flare, defined as recurrence of clinical synovitis after a DMARD-free status of ≥1 year, and 45 autoantibody-positive RA patients who were unable to stop DMARD therapy (during median 10 years) were studied. Anti-cyclic citrullinated peptide 2 (anti-CCP2) IgG, IgM and RF IgM levels were measured in 587 samples obtained at diagnosis, before and after achieving DMARD-free remission.

Results 13% of anti-CCP2 IgG-positive RA patients had seroreverted when achieving remission. In RA patients with a flare and persistent disease this was 8% and 6%, respectively (p=0.63). For anti-CCP2 IgM and RF IgM, similar results were observed. Evaluating the estimated slope of serially measured levels revealed that RF levels decreased more in patients with than without remission (p<0.001); the course of anti-CCP2 levels was not different (p=0.66).

Conclusions Sustained DMARD-free status in autoantibody-positive RA was not paralleled by an increased frequency of reversion to autoantibody negativity. This form of immunological remission may therefore not be a treatment target in patients with classified RA.

  • rheumatoid arthritis
  • autoantibodies
  • sustained DMARD-free remission

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  • Handling editor Josef S Smolen

  • Contributors DMB, LEB, RT and AvdH-vM contributed to the conception and study design. DMB analysed the data. DMB, RT and AvdH-vM contributed to interpretation of the data. DMB and AvdH-vM wrote the first version of the manuscript and LEB and RT revised it critically. DMB, LEB, RT and AvdH-vM read and approved the final manuscript.

  • Funding This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Starting grant, agreement No 714312), the Dutch Arthritis Foundation and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777357. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the local medical ethics committee, which is named ‘Commissie Medische Ethiek’. All patients signed informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.