With rheumatoid arthritis affecting nearly 20 million people worldwide, global medical societies are increasingly focusing on initiating effective treatment strategies earlier to reduce disease burden. Today, we are comparing the latest clinical practice guidelines from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) regarding treatment of rheumatoid arthritis.
The rheumatoid arthritis treatment side-by-side comparison, featured below, showcases recommendations from both societies on treatment initiation, methotrexate (MTX) administration, treatment modification, and more. For the most thorough explanation of these guidelines, visit the full text versions, linked in the following table.
Guidelines for Comparison
| Item | Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs | Treatment of Rheumatoid Arthritis |
|---|---|---|
| Authoring Organization | European League Against Rheumatism (EULAR) | American College of Rheumatology (ACR) |
| Publication Date | March 2026 | July 2021 |
| Links | Summary / Full Text | Overview / Full Text |
Key Takeaways
The ACR guideline features more recommendations than the EULAR guideline and features specific recommendations for particular patient populations (e.g., pulmonary disease, heart failure, nontuberculous mycobacterial lung disease, and more). Tapering DMARDs recommendations are also included in the ACR guideline.
Additionally, the ACR guideline features treatment initiation recommendations for particular patient populations (e.g., DMARD-naive patients with moderate-to-high disease activity, csDMARD-treated, but methotrexate-naive, patients with moderate-to-high disease activity, and more).
The EULAR guideline provides an activity monitoring recommendation, suggesting that disease activity monitoring should take place every one to three months, and if no improvement is noted in three months or the target has not been reached by six months, therapy should be adjusted.
The EULAR guideline features a condensed methotrexate (MTX) recommendation, whereas ACR provides four guidelines regarding MTX.
For the most detailed look and explanation of the EULAR and ACR recommendations, visit the full-text versions, through the links featured above.
Side-by-Side Comparison of Rheumatoid Arthritis Guidelines
| Item | EULAR | ACR |
|---|---|---|
| Treatment Initiation | Therapy with DMARDs should be started as soon as the diagnosis of RA is made. Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient. | Initiation of treatment in DMARD-naive patients with moderate-to-high disease activity: Methotrexate monotherapy is strongly recommended over hydroxychoroquine or sulfasalazine, bDMARD or tsDMARD monotherapy, or combination of methotrexate plus a non-TNF inhibitor bDMARD or tsDMARD. Methotrexate monotherapy is conditiaonally recommended over leflunomide, dual or triple csDMARD therapy, or combination or methotrexate plus a TNF inhibitor. Initiation of csDMARD without short-term (<3 months) glucocorticoids is conditionally recommended over initiation of a csDMARD with short-term glucocorticoids. Initaition of a csDMARD without longer-term (≥3 months) glucocorticoids is strongly recommedned over initiation of a csDMARD with longer-term glucocorticoids. Initiation of treatment in DMARD-naive patients with low disease activity: Hydroxychloroquine is conditionally recommended over other csDMARDS. Sulfasalazine is conditionally recommended over methotrexate. Methotrexate is conditionally recommended over leflunomide. Initiation of treatment in csDMARD-treated, but methotrexate-naive, patients with moderate-to-high disease activity: Methotrexate monotherapy is conditionally recommended over the combination of methotrexate plus a bDMARD or tsDMARD. A minimal initial treatment goal of low disease activity is conditinoally recommended over a goal of remission. |
| Activity Monitoring | Disease activity monitoring should be frequent in active disease (every 1-3 mo); if there is no improvement by at most 3 mo after the start of treatment or the target has not been reached by 6 mo, therapy should be adjusted; when the target is sustained, monitoring can be less frequent. | N/A |
| MTX Administration | MTX should be part of the first treatment strategy; in patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered. | Oral methotrexate is conditionally recommended over subcutaneous methotrexate for patients initiating methotrexate. Initiation/titration of methotrexate to a weekly dose of at least 15 mg within 4 to 6 weeks is conditionally recommended over initiation/titration to a weekly dose of <15 mg. A split dose of oral methotrexate over 24 hours or subcutaneous injections, and/or an increased dose of folic/folinic acid, is conditionally recommended over switching to alternative DMARD(s) for patients not tolerating oral weekly methotrexate. Switching to subcutaneous methotrexate is conditionally recommended over the addition of/switching to alternative DMARD(s) for patients taking oral methotrexate who are not at target. |
| Treatment Modification | Short-term glucocorticoids 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. After glucocorticoids have been discontinued and a patient is in sustained remission, continuation of DMARDs (bDMARDs/tsDMARDs and/or csDMARDs) is recommended, but dose reduction may be considered. If the treatment target is not achieved with the csDMARD strategy, a bDMARD should be added; JAK inhibitors may be considered, but pertinent risk factors* must be taken into account. bDMARDs/tsDMARDs should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, IL-6 pathway inhibitors and JAK inhibitors may have some advantages compared with other bDMARDs. | A TTT approach is strongly recommended over usual care for patients who have not been previously treated with bDMARDs or tsDMARDs. A TTT approach is conditionally recommended over usual care for patients who have had an inadequate response to bDMARDs or tsDMARDs. Addition of a bDMARD or tsDMARD is conditionally recommended over triple therapy for patients taking maximally tolerated doses of methotrexate who are not at target. Switching to a bDMARD or tsDMARD of a different class is conditionally recommended over switching to a bDMARD or tsDMARD belonging to the same class for patients taking a bDMARD or tsDMARD who are not at target. Addition of/switching to DMARDs is conditionally recommended over continuation of glucocorticoids for patients taking glucocorticoids to remain at target. Addition of/switching to DMARDs (with or withou IA glucocorticoids) is conditionally recommended over the use of IA glucocorticoids alone for patients taking DMARDs who are not at target. |
| Tapering DMARDs | N/A | Continuation of all DMARDs at their current dose is conditionally recommended over a dose reduction of a DMARD. Dose reduction is continually recommended over gradual discontinuation of a DMARD. Gradual discontinuation is conditionally recommended over abrupt discontinuation of a DMARD. Gradual discontinuation of sulfasalazine is conditionally recommended over gradual discontinuation of hydroxychloroquine for patients taking triple therapy who wish to discontinue a DMARD. Gradual discontinuation of methotrexate is conditionally recommended over gradual discontinuation of the bDMARD or tsDMARD for patients taking methotrexate plus a bDMARD or tsDMARD who wish to discontinue a DMARD. |
| Recommendations for Specific Patient Populations | N/A | Subcutaneous Nodules: Methotrexate is conditionally recommended over alternative DMARDs for patients with subcutaneous nodules who have moderate-to-high disease activity. Switching to a non-methotrexate DMARD is conditionally recommended over continuation of methotrexate for patients taking methotrexate with progressive subcutaneous nodules. Pulmonary Disease: Methotrexate is conditionally recommended over alternative DMARDs for the treatment of inflammatory arthritis for patients with clinically diagnosed mild and stable airway or parenchymal lung disease who have moderate-to-high disease activity. Heart Failure: Addition of a non–TNF inhibitor bDMARD or tsDMARD is conditionally recommended over addition of a TNF inhibitor for patients with NYHA class III or IV heart failure and an inadequate response to csDMARDs. Switching to a non–TNF inhibitor bDMARD or tsDMARD is conditionally recommended over continuation of a TNF inhibitor for patients taking a TNF inhibitor who develop heart failure. Lymphoproliferative Disorder: Rituximab is conditionally recommended over other DMARDs for patients who have a previous lymphoproliferative disorder for which rituximab is an approved treatment and who have moderate-to-high disease activity. Hepatitis B Infection: Prophylactic antiviral therapy is strongly recommended over frequent monitoring alone for patients initiating rituximab who are hepatitis B core antibody positive (regardless of hepatitis B surface antigen status). Prophylactic antiviral therapy is strongly recommended over frequent monitoring alone for patients initiating any bDMARD or tsDMARD who are hepatitis B core antibody positive and hepatitis B surface antigen positive. Frequent monitoring alone is conditionally recommended over prophylactic antiviral therapy for patients initiating a bDMARD other than rituximab or a tsDMARD who are hepatitis B core antibody positive and hepatitis B surface antigen negative. Nonalcoholic Fatty Liver Disease: Methotrexate is conditionally recommended over alternative DMARDs for DMARD-naive patients with nonalcoholic fatty liver disease, normal liver enzymes and liver function tests, and no evidence of advanced liver fibrosis who have moderate-to high disease activity. Persistant Hypogammagloubulinemia Without Infection: In the setting of persistent hypogammaglobulinemia without infection, continuation of rituximab therapy for patients at target is conditionally recommended over switching to a different bDMARD or tsDMARD. Previous Serious Infection: Addition of csDMARDs is conditionally recommended over addition of a bDMARD or tsDMARD for patients with a serious infection within the previous 12 months who have moderate-to-high disease activity despite csDMARD monotherapy. Addition of/switching to DMARDs is conditionally recommended over initiation/dose escalation of glucocorticoids for patients with a serious infection within the previous 12 months who have moderate-to-high disease activity. Nontuberculous Mycobacterial Lung Disease: Use of the lowest possible dose of glucocorticoids (discontinuation if possible) is conditionally recommended over continuation of glucocorticoids for patients with nontuberculous mycobacterial lung disease. Addition of csDMARDs is conditionally recommended over addition of a bDMARD or tsDMARD for patients with nontuberculous mycobacterial lung disease who have moderate-to-high disease activity despite csDMARD monotherapy. Abatacept is conditionally recommended over other bDMARDs and tsDMARDs for patients with nontuberculous mycobacterial lung disease who have moderate-to-high disease activity despite csDMARDs. |
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