Conference Coverage

EULAR revises its RA management recommendations



Pending 2019 revisions to the EULAR recommendations for managing rheumatoid arthritis may be most notable for two discussed changes that were tabled: No change to designating methotrexate the first disease-modifying drug to prescribe, before any biologic drug, and no adoption of imaging criteria to determine whether a patient is in remission.

Dr. Josef S. Smolen, professor of medicine, Medical University of Vienna Mitchel L. Zoler/MDedge News

Dr. Josef S. Smolen

“Imaging with ultrasound or MRI is out” as a remission criterion. “It’s high risk and a waste of resources,” declared Josef S. Smolen, MD, head of the EULAR writing panel, in the most forceful declaration he made while presenting the pending recommendation revision at the European Congress of Rheumatology.

Dr. Smolen’s strong warning against an imaging parameter when treating RA patients toward a remission target was no surprise, as he had already voiced this opinion in an editorial he coauthored earlier this year (JAMA. 2019 Feb 5;321[5]:457-8). The editorial cited data from three independent studies that compared an RA treatment strategy that used an imaging measure of joint inflammation as a treatment target along with clinical assessment against clinical assessment alone. All three studies found no benefit from ultrasound or MRI for defining a treatment goal, and two of the studies showed evidence for harm. “Using imaging to guide therapy led to prescription of potentially harmful medicines without differences in the primary outcomes, but at high costs and potential burden of unnecessary treatment changes and risks for patients,” noted Dr. Smolen and his coauthor in the editorial.

The report that this editorial addressed (JAMA. 2019 Feb 5;321[5]:461-72) also provided some of the most recent evidence for the second omission from the new revision that Dr. Smolen called out: No change to the recommendation to use methotrexate as initial treatment for any RA patient. “We continue to say that methotrexate is the first treatment strategy. There is no new evidence that any biological treatment is better than methotrexate, so there is no change,” said Dr. Smolen, professor of medicine at the Medical University of Vienna, who also led the EULAR writing panel for the immediately preceding set of RA treatment recommendations first unveiled 3 years before (Ann Rheum Dis. 2017 Jun;76[6]:960-77).

Perhaps the most notable changes to the recommendations are the way they handle targeted-synthetic disease-modifying antirheumatic drugs (tsDMARDs), a class that currently is synonymous with the Janus kinase (JAK) inhibitors. “Because of new evidence we have lifted up the tsDMARDs” so that no preference is given to biologic DMARDs over the ts class as happened in the 2016 version, Dr. Smolen said. Another revision to this recommendation was to change the addition of either a biologic or tsDMARD to a patient not fully responsive to a conventional-synthetic (cs) DMARD and with poor prognostic factors from a “should be considered” to a “should be added” recommendation.

Another way in which the pending revision uplifted tsDMARDs was in the wording for the recommendation that deals with patients who do not respond to a first tumor necrosis factor (TNF) inhibitor plus methotrexate or another csDMARD, and now lists as the first option switching to a biologic or tsDMARD with a different mode of action followed by a different TNF inhibitor, a reversal of order from before when a different TNF inhibitor got first mention. This order change was a modest revision that reflected observational evidence that was modestly persuasive that switching to an agent with a different mechanism of action is often the most effective approach, Dr. Smolen said.

The new recommendations also reaffirmed the eleventh recommendation from the 2016 version, which called for tapering of the biologic or tsDMARD from a patient in remission while retaining the csDMARD, usually methotrexate. Dr. Smolen cited new evidence in favor of this approach (Ann Rheum Dis. 2019 Jun;78[6]:746-53), which allowed the writing panel to upgrade the evidence supporting this recommendation to the A level. The concept of tapering down the biologic or tsDMARD for a patient in sustained remission while maintaining the csDMARD was “fully confirmed” in a recent report, he added. The writing panel also upticked its rating of the evidence in favor of cautiously tapering the csDMARD in patients who maintain remission on just a csDMARD.

One final element in the pending revision called out a newly identified safety signal, an increased risk for venous thromboembolism among patients on certain high dosages of JAK inhibitors, especially in patients with increased risk for venous thromboembolism. This new safety concern adds to the already-described increased risk for herpes zoster from JAK inhibitors, especially in Japanese and Korean populations, Dr. Smolen said. In general, more long-term safety data for JAK inhibitors are needed.

The draft update also added one new overarching principle: “Patients require access to multiple drugs with different modes of action to address the heterogeneity of RA, and patients may require multiple, successive treatments throughout life.” Overall, pending changes to the RA recommendations were limited because “the EULAR recommendations have achieved a steady state of the art” for defining whom to treat, treatment targets, and appropriate treatment strategies, Dr. Smolen said.

Dr. Smolen had been a consultant to or a speaker on behalf of several drug companies.

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