New Guidelines for Treating Rheumatoid Arthritis With Drug Therapies Announced

Rheumatoid arthritis (RA), the most common type of inflammatory arthritis, affects more than a million Americans — about three-quarters of them women. Symptoms of rheumatoid arthritis (RA) include joint tenderness, swelling, and pain. The disease is progressive and can be debilitating, which is why experts are always on the hunt for the best treatment regimens.

Now, after a panel exhaustively examined the latest research, the American College of Rheumatology (ACR) has developed new guidelines for the medical treatment of RA. The guidelines were published in Arthritis Care & Research in July 2021, after a draft was first released to physicians and the media on November 9, 2020.

First Update to RA Treatment Guidelines in 5 Years

The recommendations update previous guidelines from 2015, continuing the ACR’s practice of reevaluating and revamping its guidelines every five years, according to Liana Fraenkel, MD, MPH, an adjunct professor of medicine at Yale University School of Medicine in New Haven, Connecticut, and the lead investigator for the update.

Rheumatoid Arthritis Treatment Has Advanced Significantly in Recent Years

RA treatments have several different goals, according to the ACR: reduce symptoms, including pain; prevent joint damage; enhance a patient’s function and quality of life; and lessen complications of the disease.

The primary treatment for RA has long centered on synthetic disease-modifying antirheumatic drugs, known as DMARDs. This includes older drugs like methotrexate and sulfasalazine as well as newer biologics and JAK inhibitors.

All these medicines, along with quality testing and other management tools, have transformed the treatment of RA, said Don Thomas, MD, a board-certified rheumatologist in Greenbelt, Maryland, at a press conference in 2020 announcing the draft report. While years ago, many of his RA patients were debilitated and in wheelchairs, today most are in remission or experience low levels of disease.

Methotrexate: The Tried-and-True RA Drug Remains a Mainstay

The guidelines emphasize that methotrexate should remain the cornerstone of treatment for RA. Instead of rapidly switching a patient to another DMARD if the drug is not sufficient, doctors should aim to find a methotrexate regimen that works (which may include pairing methotrexate with other DMARDs).

The guidelines are definitive in this regard. Methotrexate is strongly recommended over hydroxychloroquine or sulfasalazine as a first-line drug for people with moderate to high disease activity, it states. It is also strongly recommended over beginning with a biologic drug.

An article in the March 2017 issue of Open Access Rheumatology, for instance, offers a range of options physicians should try to increase a person's success with methotrexate. They can continue to increase oral doses of the drug, which, the paper observes, “does not appear to compromise safety or tolerability.” If even that proves inadequate, the drug can be injected. Methotrexate is also effective when combined with other DMARDS, the paper notes.

Steroid Use for Rheumatoid Arthritis Treatment Should Be Minimized

One important shift from prior guidance is an emphasis that glucocorticoids, or steroids, should be prescribed as infrequently as possible.

Steroids are often used as a bridge therapy when a patient is first diagnosed, before their DMARD has time to work. But steroids come with many risks, including infection, weight gain, bone fractures, and osteoporosis. Because of these serious side effects, the guideline recommends that doctors curtail their use.

The panel acknowledged that steroids are often necessary to act as this bridge, but that their toxicity “was judged to outweigh potential benefits," and therefore they “should be limited to the lowest effective dose for the shortest duration possible.”

At the 2020 press conference, Dr. Fraenkel emphasized that "doctors should try to push the needle away from using prednisone as frequently as we do.”

There Is No Safe Steroid Dose

The problem is that research continues to show serious side effects can occur even with low amounts of the drug, says John Davis III, MD, a rheumatologist at the Mayo Clinic in Rochester, Minnesota, who was not involved in drafting the guidelines. “There is no safe steroid dose,” he says.

“The advantages of steroids is that they work quickly, and people feel better on them,” notes Lynn Ludmer, MD, a rheumatologist at Mercy Hospital in Baltimore who was also not involved with the guideline development. But this is their downside, too: Patients feel so good they can find it hard to taper off.

Step Therapy Is Not Always the Best Approach for Successful RA Care

In the 2015 guidelines, doctors were advised to escalate to triple therapy — a combination of methotrexate, sulfasalazine, and hydroxychloroquine — before starting a biologic in patients whose disease was uncontrolled. The new guidelines reverse this, recommending that rheumatologists add a biologic or targeted synthetic DMARD instead of switching to triple therapy.

According to the new guidelines, consensus on this recommendation was not as easily achieved as for most others. “The decision on whether patients with an inadequate response to methotrexate should escalate to a [biologic] DMARD, [targeted synthetic] DMARD, or triple therapy engendered much discussion with contrasting points of view,” the researchers wrote.

Ultimately, the recommendation to bypass triple therapy was made “because of the more rapid onset of benefit and concerns related to the poor tolerability and durability of triple therapy in real-world practice.”

The Move From Step Therapy Is in Response to Patients and Patient Advocates

This recommendation was driven by patients, Fraenkel said at the press conference. Patients who are suffering want to move ahead with a biologic so they can quickly feel better. “What physicians consider a short amount of time, patients do not,” she said.

Dr. Thomas notes that patients also dislike the intense regimen of the medicines (three separate drugs, taken more than once every day) and also the many tests, from blood labs to eye exams, they must regularly undertake on triple therapy. As a clinician, he said at the press conference, “I’m so thankful for this recommendation.”

In some cases, insurance companies require patients to try and fail triple therapy before moving to a biologic. Dr. Ludmer feels strongly that different patients have different needs, and that doctors know each individual patient best. “Insurers don’t always allow for individualizing a treatment. Cost is a factor, but the decision of what drugs are best for patients should be data driven, not insurance driven,” she says.

A Treat-to-Target Approach Is Adopted

To optimize the dose of methotrexate and any subsequent additional DMARDs, the panel recommends a treat-to-target approach. This is where goals are agreed upon at the start by the practitioner and the patient, who is then systematically monitored at regular intervals to determine if the targets are being met. If they are not, doses or medications can be altered.

This approach is the best way to prevent joint damage as well as other serious conditions, such as cardiovascular disease and osteoporosis, the panel explained.

Because remission may not be a realistic goal for many, the panel suggests a wise treat-to-target goal is low disease activity.

Evidence for Effective Drug Tapering Is Low

The panel noted that people who stop their medications risk flares and potential long-term joint damage.

For this reason, they recommend that people stay on at least one DMARD at a therapeutic dose.

Those who have reached their target (low disease activity or remission) for at least six months may attempt to taper their medicine if they and their physician feel it is necessary.

“Continuation of all DMARDs at their current dose is conditionally recommended over a dose reduction of a DMARD, dose reduction is conditionally recommended over gradual discontinuation of a DMARD, and gradual discontinuation is conditionally recommended over abrupt discontinuation of a DMARD for patients who are at target for at least 6 months,” the guidelines state.

Guidelines Add Specifics for Certain Patient Subgroups

The final section of the guidelines address certain specific subgroups of people with RA.

For instance, the panel conditionally recommends that certain people with pulmonary disease take methotrexate over alternative DMARDs, even though lung disease is a risk factor for methotrexate-related pneumonitis, because it is so effective at quelling RA.

And people with certain types of heart failure are conditionally recommended to add a non-TNF inhibitor biologic or targeted synthetic DMARD over a TNF inhibitor if they need an additional medicine.

The certainty of evidence for these subgroup recommendations was deemed by the panel to be very low, however.