Since their first publication in 2010, the EULAR recommendations for the usage of disease-modifying anti-rheumatic treatments (DMARDs) in individuals with RA have change into a most vital publication in the sphere, and their updates are relied upon by many healthcare professionals, skilled organisations and other stakeholders to supply an up-to-date and robust evaluation on an optimal approach to the applying of accessible treatment options in clinical practice. The recommendations were last updated in 2019, and there have been no recent drug classes released since then; nevertheless, two key aspects warranted revisiting this fifth version of the document.
Firstly, in early 2022 a randomized, controlled clinical trial in RA patients chosen for various risk aspects showed a better rate of major cardiovascular events and malignancies in those receiving tofacitinib, a Janus kinase inhibitor (JAKi) in comparison with tumour necrosis factor inhibitors; indeed, already in 2021 the US Food and Drug Administration (FDA) released a warning on these risks. As well as, the 2021 update of the RA management guidelines from the American College of Rheumatology (ACR), discouraged the usage of glucocorticoids, reasoning that the toxicity outweighs the advantages.
The updated EULAR recommendations were developed by a multidisciplinary task force of rheumatologists, other health professionals, and patient research partners, including infectious disease and epidemiology specialists. The data relies on evidence collected from three systematic reviews across efficacy and safety of each DMARDs and glucocorticoids.
The recommendations were already presented on the EULAR Congress in June 2022 (in Copenhagen) and the complete paper which incorporates all details of the discussion process for each item is now being published within the Annals of the Rheumatic Diseases online on November… 2022. The recommendations include 5 overarching principles and 11 recommendations on the usage of DMARDs, including conventional synthetic, biologic, and targeted synthetic agents, in addition to glucocorticoids. Guidance on monotherapy, combination therapy, treat-to-target, and tapering strategies can also be provided. The final principles say that treatment of RA patients should aim at the perfect care and should be based on a shared decision between the patient and the rheumatologist – who’s the one that should primarily look after individuals with RA. Treatment decisions are based on disease activity, issues of safety and other patient aspects, akin to comorbidities and progression of structural damage. But RA also incurs high individual, medical and societal costs, all of which ought to be considered in its management. The principles also highlight that patients require access to multiple drugs with different modes of motion to deal with the heterogeneity of their disease, they usually may require multiple successive therapies throughout life.
The person recommendations outline that DMARD treatment ought to be began as soon as possible after the RA diagnosis is made, with an aim of reaching sustained remission or low disease activity. The core suggestion for initial treatment with methotrexate plus glucocorticoids is retained from earlier versions. For individuals who have an insufficient response to this therapy inside 3 (significant improvement) to six (goal attainment) months, further lines of treatment ought to be based on stratification in keeping with individual risk aspects. This requires sufficiently frequent monitoring, which ought to be performed a minimum of every 3 months in individuals with lively disease. Importantly, for individuals who achieve sustained remission, DMARDs could also be tapered but shouldn’t be stopped.
One minor change to the previous version is that, in step with the respective SLR results, the group continues to recommend the consideration of the addition of short-term glucocorticoids when initiating or changing csDMARDs, but emphasizes more strongly that they ought to be tapered and discontinued as quickly as possible. A newly amended suggestion also outlines that only after glucocorticoids have been discontinued and a patient is in sustained remission, dose reduction of DMARDs could also be considered, whether or not they are conventional synthetic, biologic, or targeted synthetic agents.
Of note, the most important change is that JAK inhibitors, while still placed at the identical level as bDMARDs, should only be used if risk aspects for cardiovascular or malignant diseases have been considered; lots of these risk aspects are detailed within the respective a part of the suggestion. Which means that bDMARDs, regardless of their mode of motion, ought to be preferred over JAK inhibitors in RA patients with risk aspects for malignancy or major adversarial cardiovascular events. On this respect, EULAR welcomes the recently published recommendations for JAKi by the European Medicine Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC), as they’re in step with this 2022 update of the EULAR recommendations.
EULAR consider these recommendations are the clearest yet, and represent a logical summary of accumulating evidence. It’s hoped that the clearer the data provided in recommendations, the higher they might be followed by clinicians.
Source:
European Alliance of Associations for Rheumatology, EULAR
Journal reference:
Smolen, J.S., et al. (2022) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Annals of the Rheumatic Diseases. doi.org/10.1136/ard-2022-223356.