The American College of Rheumatology (ACR) recently released updated guidelines for the pharmacologic management of rheumatoid arthritis (RA). The full report has been published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology

Overall, the updated guidelines include treatment with disease-modifying antirheumatic drugs (DMARDs), including biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs); the use of glucocorticoids (GCs); and treatment options for certain high-risk populations. Of a total of 44 recommendations, which were developed based on the Grading of Recommendations Assessment and Development and Evaluation (GRADE) methodology, 7 were strong and 37 were conditional. However, consensus on both the strong and conditional recommendations was achieved by a 70% level of agreement by the voting panel.

Recommendations for DMARD Initiation

Strong Recommendations
• For DMARD-naive patients with moderate to high disease activity, methotrexate (MTX) is recommended over hydroxychloroquine (HCQ) or sulfasalazine, b/tsDMARDs, and MTX plus b/tsDMARD combination therapy.
• Initiation of csDMARDs without longer-term (≥3 mo) GCs is recommended over initiation with longer-term GCs.
Conditional Recommendations
• For DMARD-naive patients with moderate to high disease activity, MTX is recommended over leflunomide, csDMARDs, and MTX plus tumor necrosis factor inhibitor (TNFi) combination therapy.
• For DMARD-naive patients with low disease activity, HCQ is recommended over other csDMARDs; sulfasalazine over MTX; MTX over leflunomide.
• For csDMARD-treated but MTX-naive patients, MTX monotherapy is recommended over MTX plus b/tsDMARD combination therapy
• Initiation of csDMARDs without short-term (<3 mo) GCs is recommended over initiation with short-term GCs.

Recommendations for MTX Administration

Conditional Recommendations
• For patients initiating MTX, oral MTX is recommended over subcutaneous MTX.
• Initiation/titration of MTX to a weekly dose of at least 15 mg within 4 to 6 weeks is recommended over initiation/titration of MTX to less than 15 mg/week.
• For patients with intolerance to oral weekly MTX, a split dose of oral or subcutaneous injections of MTX over a 24-hour period and/or an increased dose of folic/folinic acid is recommended over switching to alternative DMARDs.
• For patients receiving oral MTX and not at target, switching to subcutaneous MTX is recommended over addition of or switching to alternative DMARDs. 

Recommendations for Treatment Modifications

Strong Recommendations
• For patients not previously treated with b/tsDMARDs, a treat-to-target (TTT) approach is recommended over standard care.
Conditional Recommendations
• For patients with an inadequate response to b/tsDMARDs, a TTT approach is recommended over standard care.
• A minimal initial treatment goal of low disease activity is recommended over a goal of remission.
• For patients receiving maximally tolerated doses of MTX and not at target, addition of a b/tsDMARD is recommended over triple therapy.
• For patients receiving b/tsDMARDs and not at target, switching to a b/ts DMARD of a different class is recommended over switching to the same class.
• For patients receiving GCs to remain at target, addition of or switching to DMARDs is recommended over continuation of GCs.
• For patients receiving DMARDs and not at target, addition of or switching to DMARDs with or without intra-articular (IA) GCs is recommended over use of IA GCs alone.

Recommendations for Tapering DMARDs

Conditional Recommendations
• Continuation of a DMARD at the current dose is recommended over dose reduction; dose reduction is recommended over gradual discontinuation; gradual discontinuation is recommended over abrupt discontinuation of a DMARD.
• For patients receiving triple therapy who intend to discontinue a DMARD, gradual discontinuation of sulfasalazine is recommended over that of HCQ.
• For patients receiving MTX plus a b/tsDMARD who intend to discontinue the DMARD, gradual discontinuation of MTX is recommended over discontinuation of the b/tsDMARD.

Recommendations for Specific Patient Populations

Conditional Recommendations
Subcutaneous Nodules
• For patients with moderate to high disease activity, MTX is recommended over alternative DMARDs.
• For patients with progressive disease receiving MTX, switching to a non-MTX DMARD is recommended over continuation of MTX.
Pulmonary Disease
• For patients with mild or stable airway or parenchymal lung disease with moderate to high disease activity, MTX is recommended over alternative DMARDs for inflammatory arthritis treatment.
Heart Failure
• For patients with New York Heart Association (NYHA) class 3 or 4 heart failure with an inadequate response to csDMARDs, the addition of a non-tumor necrosis factor inhibitor (TNFi) b/tsDMARD is recommended over the addition of a TNFi.
• For patients receiving a TNFi who develop heart failure, switching to a non-TNFi b/tsDMARD is recommended over continuation of a TNFi.
Lymphoproliferative Disorder
• For patients with a previous lymphoproliferative disorder with moderate to high disease activity, rituximab is recommended over other DMARDs.
Nonalcoholic Fatty Liver Disease (NAFLD)
• For DMARD-naive patients with NAFLD, normal liver enzymes and liver function tests, and no advanced liver fibrosis, with moderate to high disease activity, MTX is recommended over alternative DMARDs.
Persistent Hypogammaglobulinemia Without Infection
• For patients at target, continuation of rituximab is recommended over switching to a different b/tsDMARD.
Previous Serious Infection
• For patients with a serious infection in the previous 12 months with moderate to high disease activity despite csDMARD monotherapy, the addition of csDMARDs is recommended over the addition of a b/tsDMARD.
• For these patients, addition of or switching to DMARDs is recommended over the initiation/dose escalation of GCs.
Nontuberculous Mycobacterial Lung Disease
• Lowest dose or discontinuation of GCs is recommended over continuation of GCs.
• For patients with moderate to high disease activity despite csDMARD monotherapy, addition of csDMARDs is recommended over the addition of a b/tsDMARD. However, abatacept is recommended over other b/tsDMARDs.
Hepatitis B Infection – Strong Recommendations
• For patients who test positive for the hepatitis B core antibody (regardless of hepatitis B surface antigen status) and initiating rituximab, prophylactic antiviral therapy is recommended over frequent monitoring alone.
• For patients who test positive for both the hepatitis B core antibody and the surface antigen and initiating b/ts DMARDs, prophylactic antiviral therapy is recommended over frequent monitoring alone.

Hepatitis B Infection – Conditional Recommendation
• For patients who test positive for the hepatitis B core antibody and negative for the hepatitis B surface antigen and initiating a bDMARD other than rituximab or a tsDMARD, frequent monitoring alone is recommended over prophylactic antiviral therapy.

Overall, the authors concluded, “[T]his update includes recommendations related to initiation and adjustment of DMARD therapy in patients with RA. It also emphasizes the importance of minimizing use of [GCs]. It is expected that additional data may modify the direction and/or strength of specific recommendations. The ACR will update the recommendations and answer these and other questions as new data are published.”


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Note: A podcast episode is available highlighting the important updates of the 2021 ACR guidelines for the treatment of RA, as presented at the ACR 2020 Annual Meeting.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol; Arthritis Care Res. Published online June 8, 2021. doi:10.1002/acr.24596