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EULAR recommendations for DMARDs in rheumatoid arthritis Posted 26/06/2020

The European League Against Rheumatism (EULAR) has updated its recommendations on the management of rheumatoid arthritis (RA) using synthetic and biological disease-modifying antirheumatic drugs (DMARDs) [1].

EULAR developed its first recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological DMARDs in 2010. This update, according to EULAR, takes account of the most recent developments in the field, and covers the following topics:

  • Newly licensed drugs
  • Long-term efficacy and safety of long approved agents
  • Comparative effectiveness studies
  • Therapeutic targets and treatment strategies
  • Consideration of safety aspects and costs
  • Specific items of the 2016 research agenda that have been accomplished during the last few years of the decade

A steering committee and a task force worked on this update of the EULAR recommendations for the management of RA. The steering committee, which included eight rheumatologists, one patient representative and two fellows, performed the systematic literature research (SLR). The task force consisted of 47 individuals, including the steering committee members, and included rheumatologist experienced in RA from 15 European countries, two rheumatologists from Asia, two from Latin America and two from North America.

The results of the SLR was presented to the task force and updates to the recommendations were voted on, with changes to overarching principles requiring a majority of ≥75%. New recommendations were immediately accepted when ≥75% or more of the task force members voted for it. If this result was not achieved, the respective text was amended and subjected to a second ballot, for which a 67% majority was required. If this ballot was not successful, the text was further amended and subjected to a third ballot for which a simple (>50%) was required; failing that, the proposal was rejected.

The 2019 update of the EULAR RA management recommendations reflects the balance of clinical, functional and structural efficacy; safety; costs; and patients’ perceptions as evaluated by the task force. The recommendations include the following five overarching principles, with the fourth being newly added:
Treatment of patients with RA should aim at the best care and must be based on a shared decision between the patient and the rheumatologist.
     A. Treatment of patients with RA should aim at the best care and must be based on a shared decision between
          the patient and the rheumatologist.
     B. Treatment decisions are based on disease activity, safety issues and other patient factors, such as comorbidities
          and progression of structural damage.
     C. Rheumatologists are the specialists who should primarily care for patients with RA.
     D. Patients require access to multiple drugs with different MOAs to address the heterogeneity of RA;
          they may require multiple successive therapies throughout life.
     E. RA incurs high individual, medical and societal costs, all of which should be considered in its management by
          the treating rheumatologist.

The task force’s discussions also resulted in 12 recommendations. The first seven recommendations, as well as recommendations 9 and 12, remain unchanged. New/changed recommendations are highlighted in bold:

     1.  Therapy with DMARDs should be started as soon as the diagnosis of RA is made.
     2.  Treatment should be aimed at reaching a target of sustained remission LDA in every patient.
     3.  Monitoring should be frequent in active disease (every 1–3 months); if there is no improvement by at most
          3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted.
     4.  Methotrexate (MTX) should be part of the first treatment strategy.
     5.  In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered
          as part of the (first) treatment strategy.
     6.  Short-term GC should be considered when initiating or changing conventional synthetic (cs)DMARDs, in different
          dose regimens and routes of administration, but should be tapered as rapidly as clinically feasible.
     7.  If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors,
          other csDMARDs should be considered.
     8. If the treatment target is not achieved with the first csDMARD strategy and poor prognostic factors are
          present, a biological (b)DMARD or a targeted synthetic (ts)DMARD should be added.
     9.  bDMARDs and tsDMARDs should be combined with a csDMARD; in patients who cannot use csDMARDs as
          co-medication, interleukin 6 (IL-6) pathway inhibitors and tsDMARDs may have some advantages compared with
          other bDMARDs.
   10. If a bDMARD or tsDMARD has failed, treatment with another bDMARD or a tsDMARD should be
          considered; if one tumour necrosis factor inhibitor (TNFi) therapy has failed, patients may receive
          an agent with another mode of action or a second TNFi.
   11.  If a patient is in persistent remission after having tapered glucocorticoids, one can consider
          tapering bDMARDs or tsDMARDs, especially if this treatment is combined with a csDMARD.
   12.  If a patient is in persistent remission, tapering the csDMARD could be considered.

The recommendations are ordered in terms of a sequential treatment strategy from the time point of diagnosis and the requirement to immediately start a DMARD therapy. EULAR does not distinguish between originator and biosimilar DMARDs, including biosimilar DMARDs in its recommendations for TNFi inhibitor bDMARDs.

The task force concludes that these recommendations provide rheumatologists, patients, health professionals and other stakeholders ‘with the most recent evidence regarding the management of patients with RA’ and ‘will allow optimal treatment of patients with RA’. The authors expect another update of the recommendations to be necessary in about 3-4 years.

Conflict of interest
The authors of the research paper [1] reported conflict of interest, including having received grants and honoraria from pharmaceutical companies. For full details of the authors’ conflict of interest, see the research paper [1].

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Reference
1. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685‐99.

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