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Cohort study shows improvement during 25 years of RA treatment

Presented by
Dr Xanthe Matthijssen, Leiden University Medical Center, the Netherlands
EULAR 2019
Improvements in treatment strategies during the last 25 years have led to lower disease activity, more sustained drug-free remission, and better physical functioning of rheumatoid arthritis (RA) patients [1]. ACPA-positive patients benefited most from these improvements.

Broadly speaking, RA consists of two distinct disease subtypes that are characterised by the presence or absence of RA-related auto-antibodies, of which the presence of anti-citrullinated protein antibodies (ACPA) is most specific for RA. Both subtypes have known differences in the severity of the disease course, and ACPA-positive and ACPA-negative RA may differ in their treatment responses. “What we all know, is that RA treatment has improved drastically with earlier treatment and better medication,” said Dr Xanthe Matthijssen (Leiden University Medical Center, the Netherlands). “However, the difference in treatment response between these two subtypes is still unclear and treatment guidelines do not make a clear distinction in RA treatment. Almost all start with methotrexate.”

Dr Matthijssen aimed to investigate the influence of advanced treatment strategies on disease activity, sustained drug-free remission, and functional disability over the last 25 years among ACPA-positive and ACPA-negative RA patients included in the Leiden Early Arthritis cohort. “We used inclusion period as an instrumental variable for treatment strategy,” added Dr Matthijssen. Patients were treated in routine care, and initial and subsequent treatment changed over time (see Table). Baseline age, gender, and antibody status were not significantly different between inclusion periods. Patient assessments included swollen joint counts, the 28-joint count DAS (DAS28-ESR), and health assessment questionnaires (HAQ). Sustained drug-free remission was defined as the persistent absence of synovitis after cessation of DMARD-therapy during all available follow-up (≥1 year).

Table: Treatment strategy in Leiden Early Arthritis cohort


With 1993-1996 as a reference, the DAS28-ESR decreased in the first year and remained lower in all inclusion periods (P<0.05). Drug-free remission was achieved faster in inclusion periods 2006-2010 and 2011-2016. Additionally, HAQ over time was lower in these last two periods. There was no difference in DAS28-ESR between ACPA-positive and ACPA-negative patients in subsequent cohorts. The increased rate of sustained drug-free remission was more prominent in ACPA-positive patients than ACPA-negative patients in inclusion periods 2006-2010 and 2011-2016. HAQ over time improved specifically in ACPA-positive RA. In general, “ACPA-positive RA patients benefited a lot, whereas ACPA-negative RA patients benefited a little. Further improvements are needed for ACPA-negative RA patients,” concluded Dr Matthijssen. It is likely that the extreme immunological heterogeneity within the ACPA-negative group and overlaps with inflammatory hand osteoarthritis and other factors account for these differences [2].

  1. Matthijssen X, et al. Abstract OP0023. EULAR 2019.
  2. McGonagle D, et al. Autoimmun Rev. 2018 Nov;17(11):1115-1123.

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