Proposed RA Guidelines: Maximize Methotrexate Before Switching

Marcia Frellick

November 09, 2020

New proposed guidelines for managing rheumatoid arthritis (RA) recommend that methotrexate (MTX) be used aggressively before other treatment options.

Dr Liana Fraenkel

Previous guidelines, last updated in 2015, had not ranked the order of the treatments, said Liana Fraenkel, MD, MPH, principal investigator for the American College of Rheumatology's (ACR's) treatment guidelines.

"There's a strong emphasis on maximizing methotrexate using various means before switching to a biologic or JAK [Janus kinase] inhibitor," she said in a press conference at ACR Convergence 2020. The guidelines draft was developed collaboratively with clinicians, researchers, and patients. In addition, the authors conducted a comprehensive review of the literature.

Fraenkel, an adjunct professor at Yale School of Medicine in New Haven, Connecticut, said the exception for maximizing MTX would be for patients with low disease activity for whom treatments with other medications, such as hydroxychloroquine (HCQ) and sulfasalazine, are feasible, she said.

Stop Defaulting to Prednisone

Another recommendation urges against the use of prednisone as a default treatment.

"We should really be trying to maximize disease-modifying antirheumatic drugs [DMARDs] and try to push the needle away from using prednisone as frequently as we do," she said.

Fraenkel said the panel wanted to emphasize that "even lower doses of prednisone can be harmful."

She noted that patients on the guidelines panel said it's hard to taper off prednisone.

Don Thomas, MD, who is in private rheumatology practice in Greenbelt, Maryland, told Medscape Medical News, "I love the guidelines.

"Most of my patients are not on steroids," he said, "which is a godsend because of the great therapies we have."

He said he was glad to see support for exhausting methotrexate options first before trying new treatments.

"Too many of us are not as aggressive as we should be with using methotrexate initially," he said.

Specific Recommendations

In the proposed guidelines, MTX alone is strongly recommended over HCQ or sulfasalazine and is conditionally recommended over a conventional synthetic DMARD dual or triple combination. MTX alone is also conditionally recommended over MTX in combination with a tumor necrosis factor (TNF) inhibitor and is strongly recommended over MTX in combination with a non-TNF inhibitor, a biologic, or a targeted synthetic DMARD.

For patients with low disease activity who have not taken DMARDs, HCQ is recommended over other conventional synthetic DMARDs. Sulfasalazine is recommended over MTX, and MTX is recommended over leflunomide.

For initial treatment, oral MTX is conditionally recommended over subcutaneous administration. For patients who are not tolerating the oral version, "recommend split-dose or subcutaneous or increasing folic acid over switching to a new DMARD," she said.

Fraenkel said the oral recommendation was based largely on patient preference.

Use of Glucocorticoids

For patients who need glucocorticoids to remain at target, adding or switching DMARDs is recommended over continuing glucocorticoids, the guidelines indicate.

"For patients on DMARDs and not at target, adding or switching DMARDs with or without the use of intraarticular glucocorticoids is conditionally recommended over the use of intraarticular glucocorticoids alone," the proposed guidelines advise.


Tapering should only be considered for patients "who have been at target for at least 6 months," she said. "In these patients, continuation of all DMARDs at their current dose is conditionally recommended over any dose reduction."

Dose reduction is recommended over gradual discontinuation, and gradual discontinuation is recommended over abruptly stopping.

Fraenkel acknowledged that the level of evidence is low to very low for many of the recommendations (only 7 of 44 recommendations were classified as strong), which, she said, underscores the importance of shared decision making for RA.

She added, "We really need trials to address clinically important questions driven by patients and not simply driven by [having] a new molecule to test."

ACR says the final version of the proposed guidelines is expected to be simultaneously published in Arthritis Care and Research and Arthritis and Rheumatology by the end of the year.

These guidelines are focused on pharmacologic agents. Separate ACR guidelines will address nonpharmacologic management of RA and vaccine recommendations for inflammatory disease.

Fraenkel and Thomas have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2020 Annual Meeting: Abstract scientific session 5MO18. Presented November 11, 2020.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune and and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.