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
