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Explore This IssueOctober 2013
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MADRID—The latest European League Against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis give a somewhat greater nod to the use of combination conventional disease-modifying antirheumatic drugs (DMARDs) than past recommendations did, but leaves monotherapy with methotrexate as a perfectly acceptable first-line treatment.
The recommendations also keep all biologic DMARDs—such as tumor necrosis factor (TNF) inhibitors—as second-line treatments, according to a presentation by Josef Smolen, MD, chair of rheumatology at the Medical University of Vienna, who spoke on behalf of the 33-member task force that wrote the updated recommendations. He made his remarks in a presentation at the EULAR 2013 Annual European Congress of Rheumatology, held June 12–15.
The task force included an infectious disease specialist, a health economist, four patient representatives and three fellows who performed systematic literature reviews on synthetic DMARDs, biologic DMARDs, and safety concerns.
The task force recommends that biological DMARDs should be started, along with methotrexate, in patients who don’t respond sufficiently to conventional DMARDs and have risk factors for bad outcome. Those biologics, the task force decided, can include TNF inhibitors, abatacept, or tocilizumab.
There has been “no preference given to any agent as a first biological,” Dr. Smolen said.
The task force also adjusted its recommendations on glucocorticoid use, now saying that “low-dose glucocorticoids should be considered as part of the initial treatment strategy (in combination with one or more conventional synthetic DMARDs) for up to six months, but should be tapered as rapidly as clinically feasible.”
The task force’s recommendations also have a place for tofacitinib, saying it “may be considered after biological treatment has failed.” The recommendations were finalized before the European Medicines Agency refused marketing authorization for the drug. Tofacitinib has been approved in the U.S., Japan, and Russia.
“EULAR recommendations are of a general nature and not only intended for Europe,” Dr. Smolen said.
Changes from 2010 Recommendations
EULAR’s 2010 RA recommendations caused a stir when monotherapy was expressly recommended as first-line treatment over combination conventional synthetic DMARDs. Some rheumatologists in the field felt that the evidence justified a more prominent role for combination therapy.
In the latest recommendations, the task force recommends either “conventional synthetic DMARD monotherapy or combination therapy” in DMARD-naive patients.
“The 2010 recommendations did not intend to say that the use of combination conventional synthetic DMARD therapy was wrong, but only that it was not needed,” Dr. Smolen said. “The 2013 task force reiterates the evidence-based view that conventional synthetic DMARD monotherapy is effective.
“But based on some newer trial data on conventional synthetic DMARD combination therapy,” he continued, “the task force more explicitly endorses combination of conventional synthetic DMARDs, also, early on. Preference to combination is not given because of possible limitations in designs of these trials and conflicting trial data.”
Robert Landewe, MD, PhD, professor of rheumatology at the Academic Medical Center Amsterdam, and a task force member, acknowledged that the 2010 task force has “been bashed by many comments in the literature.”
“We felt the role of glucocorticoids in the trials that were available was dominant,” he said. “And we felt trials solely investigating DMARD combination therapy at that point in time were not convincing.”
For instance, he said, the Swefot trial, which explored triple combination therapy versus methotrexate plus infliximab after a target response was not achieved after three months of methotrexate alone, dropped its intended per-arm cohort to 130 from 200.1 Plus, it involved unblinded physicians and had reduced statistical power. Moreover, it was designed as a superiority trial, but in the end was presented as a noninferior trial.
“These factors make Swefot less appropriate for considering if triple-combo should be advocated as an option before methotrexate plus biologicals,” Dr. Landewe said.
Another trial, TEAR, set out to investigate whether new-onset RA patients should be treated with step-up therapy or immediate combination therapy. But the trial missed its primary endpoint and was beset by attrition and data were missing for 37% of the patients, Dr. Landewe said.
“Making recommendations is a process that should involve all pillars of evidence-based medicine”—including patients and clinical experience—“not only ‘science,’” Dr. Landewe said. “Even the science of randomized controlled trials is subject to interpretation.”
Thomas Collins is a freelance medical writer based in Florida.