Updated EULAR recommendations on the use of DMARDs for people with RA

Updated EULAR recommendations on the use of DMARDs for people with RA

Since their initial publication in 2010, the EULAR recommendations for the use of disease-modifying anti-rheumatic treatments (DMARDs) in people with RA have become one of the most important publications in the field, and many healthcare professionals rely on their updates from organizations and other stakeholders to provide a timely and robust analysis of an optimal approach to the use of available treatment options in clinical practice. The recommendations were last updated in 2019 and no new drug classes have been published since then; However, two key factors warranted revisiting this fifth version of the document.

First, in early 2022, a randomized, controlled clinical trial in RA patients selected for various risk factors showed a higher rate of major cardiovascular events and malignancies in patients receiving tofacitinib, a Janus kinase inhibitor (JAKi), compared to tumor necrosis factor inhibitors; In fact, the US Food and Drug Administration (FDA) issued a warning about these risks back in 2021. Additionally, the 2021 update of the American College of Rheumatology (ACR) RA management guidelines recommended against the use of glucocorticoids, citing toxicity outweighing benefits.

The updated EULAR recommendations were developed by a multidisciplinary task force of rheumatologists, other healthcare professionals and patient research partners, including infectious disease and epidemiology specialists. The information is based on evidence from three systematic reviews on the effectiveness and safety of both DMARDs and glucocorticoids.

The recommendations have already been presented at the EULAR Congress in June 2022 (in Copenhagen) and the full paper, containing full details of the discussion process for each point, will now be published online in November 2022 in the Annals of the Rheumatic Diseases. The recommendations contain 5 overarching principles and 11 recommendations for the use of DMARDs, including conventional synthetic, biological and targeted synthetic agents, as well as glucocorticoids. Guidance on monotherapy, combination therapy, treat-to-target and tapering strategies is also provided. The general principles state that treatment of RA patients must aim for the best possible care and be based on a shared decision between the patient and the rheumatologist - who is the person who should primarily care for people with RA. Treatment decisions are based on disease activity, safety considerations and other patient factors such as comorbidities and progression of structural damage. But RA also imposes high individual, medical and societal costs, all of which should be taken into account in its management. The principles also emphasize that patients need access to multiple medicines with different modes of action to manage the heterogeneity of their disease and may require multiple consecutive therapies throughout their life.

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Individual recommendations state that DMARD treatment should be started as soon as possible after diagnosis of RA with the aim of achieving sustained remission or low disease activity. The core recommendation for initial treatment with methotrexate plus glucocorticoids is retained from previous versions. For people who respond inadequately to this therapy within 3 (significant improvement) to 6 (goal achievement) months, further lines of treatment should be given based on stratification according to individual risk factors. This requires sufficiently frequent monitoring, which should be performed at least every 3 months in individuals with active disease. Importantly, DMARDs can be tapered in people who achieve sustained remission, but should not be discontinued.

A minor change from the previous version is that the group continues to recommend considering the addition of short-term glucocorticoids when initiating or changing csDMARDs, consistent with the respective SLR results, but emphasizes more strongly that these should be tapered and discontinued as quickly as possible. A newly revised recommendation also specifies that only after discontinuation of glucocorticoids and in a patient in sustained remission can a dose reduction of DMARDs be considered, regardless of whether they are conventional synthetic, biological or targeted synthetic agents.

The most important change is that JAK inhibitors, although still at the same level as bDMARDs, should only be used when risk factors for cardiovascular or malignant disease have been taken into account; Many of these risk factors are listed in the relevant part of the recommendation. This means that bDMARDs, regardless of their mode of action, should be preferred over JAK inhibitors in RA patients with risk factors for malignancies or major adverse cardiovascular events. In this context, EULAR welcomes the recently published recommendations of the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) for JAKi, as they are consistent with this update of the 2022 EULAR recommendations.

EULAR believes these recommendations are the clearest to date and represent a logical summary of the accumulating evidence. It is hoped that the clearer the information provided in the recommendations, the better they can be followed by clinicians.

Source:

European Alliance of Rheumatology Associations, EULAR

Reference:

Smolen, J.S., et al. (2022) EULAR recommendations for the treatment of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Annals of Rheumatic Diseases. doi.org/10.1136/ard-2022-223356.

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