Based on emerging new evidence and expert consensus, an international task force put together by the European League Against Rheumatism (EULAR) released updated recommendations for the management of rheumatoid arthritis (RA) with synthetic and biologic disease-modifying antirheumatic drugs (DMARDs). This report was published in Annals of the Rheumatic Diseases.
Investigators performed a systematic review of studies focused on the efficacy and safety of DMARDs as monotherapy or combination therapy, including conventional synthetic, targeted synthetic, and biologic DMARDs. The task force agreed on 5 overarching principles and 12 recommendations by devising related questions, eliciting expert opinions, and reaching consensus by vote.
Overarching Principles for Managing RA
1. According to the researchers, treatment of patients with RA should be based on shared decision-making between the patient and the treating rheumatologist. In addition, patient and provider education should be included in best care practices, which may increase adherence to medications and appropriate assessment strategies, respectively.
2. Researchers indicated that decisions regarding the treatment of patients with RA — particularly when considering biologic and targeted synthetic DMARDs — should be based on disease activity, safety issues, and other patient factors, including comorbidities and progression of structural damage.
3. Recommendations included that primary care for patients with RA should be provided by rheumatologists; it is especially important for patients with RA to receive specialty care when initiating any type of DMARD therapy.
4. The newest principle in managing patients with RA recognizes the heterogeneity of RA, in which the increasing number of drugs with different modes of action should be made accessible to patients as they may require multiple successive drug options throughout life to reach their therapeutic goal.
5. According to the researchers, RA is associated with a high economic burden to both patients and society; the treating rheumatologist should recommend drugs that are less costly compared with drugs that are more costly if efficacy and safety profiles are therapeutically similar.
Recommendations for Goals of Therapy
Therapy with DMARDs should be immediately initiated upon RA diagnosis as the disease will not remit spontaneously.
Sustained remission or low disease activity should be the primary goal in treating patients with RA, and both the American College of Rheumatology and EULAR agreed on the Boolean- and index-based definitions of remission.
Recommendations included the rapid attainment of the treatment target. It was agreed by the task force that disease activity should be assessed every 1 to 3 months; if no improvement is observed after 3 months or the target has not been achieved after 6 months, the treatment strategy should be adjusted.
Recommendations for First-Line Treatment Strategies
In treating patients with RA, methotrexate was recommended as first-line treatment. Investigators indicated that methotrexate is an efficacious conventional synthetic DMARD used as monotherapy but is also the basis for combination therapies with other DMARDs or glucocorticoids; dose escalation should occur within 4 to 6 weeks to reach a weekly dose of about 0.3 mg per kg.
If patients experience early intolerance or have a contraindication to methotrexate, the task force recommended that leflunomide or sulfasalazine be considered as part of first-line treatment strategy.
The EULAR recommended a short-term course of glucocorticoids as a bridging therapy when initiating or changing conventional synthetic DMARD therapies; once the treatment exhibits efficacy, rapidly tapering glucocorticoid use (within 3 months) is important.
Recommendations for Secondary Treatment Strategies
If the treatment target is not achieved after the first-line conventional synthetic DMARD strategy, other conventional synthetic DMARDs should be considered in the absence of poor prognostic factors. These factors include high disease activity and the presence of clinical features, as well as failure to achieve low disease activity after at least 2 conventional synthetic DMARDs.
If poor prognostic factors are present, and the treatment target is not achieved with the first conventional synthetic DMARD strategy, then the task force recommended adding a biologic DMARD or a targeted synthetic DMARD. Patient contraindications, preferences, and cost of care should be considered in deciding on combination therapy.
Recommendations for Combination Therapies
All biologic and targeted synthetic DMARDs are more efficacious in combination therapy compared with monotherapy; EULAR recommends that biologic DMARDs and targeted synthetic DMARDs be combined with a conventional synthetic DMARD. Among patients with contraindications to conventional synthetic DMARDs, interleukin-6 pathway inhibitors and targeted synthetic DMARDs may be used as comedication.
Researchers indicated that if a biologic DMARD or targeted synthetic DMARD therapy fails, treatment with another biologic DMARD or targeted synthetic DMARD should be considered. Similarly, if treatment with tumor necrosis factor inhibitor (TNFi) fails, patients may be effectively treated with a different mode of action or a second TNFi therapy.
Recommendations for Persistent Remission
If persistent remission is achieved after tapering any glucocorticoid bridging therapies, EULAR suggests that clinicians consider tapering biologic DMARDS or targeted synthetic DMARDs, especially when these therapies are combined with a conventional synthetic DMARD. Discontinuation of biologic DMARDs is often associated with flares, and tapering of biologic DMARDs may be preferred just as a dose reduction or interval increase.
Investigators indicated that if persistent remission is achieved with conventional synthetic DMARD monotherapy or if remission can be sustained after cessation of any added therapies from a combination therapy regimen, tapering the conventional synthetic DMARD may be considered.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please refer to the original reference for a full list of authors’ disclosures.
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 [published online January 22, 2020]. Ann Rheum Dis. doi:10.1136/annrhumdis-2019-216655