EULAR Issues Updated Recommendations for RA Management

An international task force established by the European League Against Rheumatism (EULAR) has updated its guidelines for the treatment of rheumatoid arthritis (RA), including 5 overarching principles and 11 specific treatment recommendations that reflect recent new drug approvals and research results since the 2019 guideline was issued.

The principles are:

• “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.
• “Treatment decisions are based on disease activity, safety issues, and other patient factors, such as comorbidities and progression of structural damage.
• “Rheumatologists are the specialists who should primarily care for patients with RA.
• “Patients require access to multiple drugs with different modes of action to address the heterogeneity of RA; they may require multiple successive therapies throughout life.
• “RA incurs high individual, medical and societal costs, all of which should be considered in its management by the treating rheumatologist.”

EULAR continues to recommend methotrexate (MTX) with glucocorticoids (GCs) as first-line treatment for RA. When patients do not show sufficient response to this therapy within 3 to 6 months, the association recommends that further treatment be based on stratification according to risk factors. Among patients with poor prognostic factors, such as the presence of autoantibodies, high disease activity, early erosions, or failure of 2 conventional synthetic (cs) DMARDs), EULAR recommends the addition of any biologic (b) DMARD to the csDMARD. After considering risks of major adverse cardiac events (MACEs), malignancies, and/or thromboembolic events, targeted synthetic (ts) DMARDs may also be considered.

“If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations,” the guideline states.

The recommendations included in the updated guideline are:

• 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.
• Treatment decisions are based on disease activity, safety issues and other patient factors, such as comorbidities and progression of structural damage.
• Rheumatologists are the specialists who should primarily care for patients with RA.
• Patients require access to multiple drugs with different modes of action to address the heterogeneity of RA; they may require multiple successive therapies throughout life.
• RA incurs high individual, medical and societal costs, all of which should be considered in its management by the treating rheumatologist.
• Therapy with DMARDs should be started as soon as RA is diagnosed.
• Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient. While there was general agreement with this recommendation, certain questions arose. “‘Sustained’ remission or low disease activity refers to the maintenance of this state for at least 6 months,” the guideline states.
• Patients should be monitored frequently—every 1 to 3 months—when in active disease. If there is no improvement after 3 months of treatment or the target has not been reached by 6 months, therapy should be adjusted. 
• MTX should be part of the first treatment strategy. 
• Among patients with a contraindication to or early intolerance of MTX, leflunomide or sulfasalazine should be considered as part of the initial treatment strategy. 
• Short-term GCs should be considered when initiating or changing csDMARDs, in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible. The guideline report notes, “[I]t must be reiterated that chronic use of GCs is neither meant nor suggested by this recommendation; therefore, ‘short term’ has been placed at the beginning of this item and the time frame is clearly defined as not more than 3 months.”
• If the first csDMARD strategy does not reach the target, other csDMARDs should be considered when poor prognostic factors are not present. The guideline notes that EULAR does not advocate combining csDMARDs, “but they also do not strongly recommend against such strategies. These recommendations are meant as a guidance document prepared by numerous experts in the field, but in daily practice and in front of an individual patient the individual rheumatologist must arrive at the best decision together with the patient.”
• If a patient with poor prognostic factors does not reach the treatment target with the first csDMARD strategy, a bDMARD should be added. This includes JAK inhibitors, with the caution that “pertinent risk factors must be taken into account…The majority of the Task Force members were of the opinion that the data on risks due to tofacitinib currently pertain only to patients at risk and that these risk factors should be clearly communicated. On the other hand, the Task Force found no evidence for greater risk of tofacitinib versus TNFi [tumor necrosis factor inhibitors] in patients without risk factors.”
• bDMARDs and tsDMARDs should be combined with a csDMARD. Among patients who cannot use csDMARDs as comedication, IL-6 inhibitors and tsDMARDs may have some advantages compared with other bDMARDs, the task force found. “No new compelling evidence was gained regarding monotherapy of bDMARDs or tsDMARDs compared with combination therapy,” the guideline states. “Therefore, the EULAR Task Force continues to advocate the continuation of MTX (or other csDMARDs) when treatment with bDMARDs or JAKi is planned.”
• If a bDMARD or tsDMARD has failed, EULAR recommends trying another bDMARD or a tsDMARD. In the case of failure of a TNFi- or IL-6 receptor inhibitor therapy, an agent with another mode of action or a second TNF- or IL-6 receptor inhibitor should be considered. 
• After GCs have been discontinued and a patient is in sustained remission, dose reduction of DMARDs (bDMARDs/tsDMARDs and/or csDMARDs) may be considered. “Importantly, though, there is also compelling evidence that stopping bDMARDs and/or csDMARDs will ultimately lead to flares in most patients. Therefore, the Task Force felt that either dose reduction or interval increase (‘spacing’) is preferred, but completely stopping may not be advisable.”

—Rebecca Mashaw

Reference:

Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3-18. https://ard.bmj.com/content/82/1/3.info