COPENHAGEN — Metho-trexate is the “anchor drug” for treating rheumatoid arthritis, and treatment should start at the time of diagnosis, according to the first European League Against Rheumatism recommendations for managing the disease.
“Methotrexate should be part of the first treatment strategy in patients with active rheumatoid arthritis [RA],” said Dr. Robert B.M. Landewé at the annual meeting of the European Congress of Rheumatology. Metho-trexate either can be monotherapy or can be used as part of combination therapy, but “methotrexate should be considered a sort of anchor drug,” said Dr. Landewé, professor of rheumatology at Maastricht (the Netherlands) University.
“This is where treatment has been for 5-10 years. There is nothing new with methotrexate as the anchor drug, except now an expert panel explicitly says it,” he said in an interview.
Dr. Landewé, an epidemiologist for the task force, and several colleagues presented the current draft of the new EULAR recommendations for RA treatment to an overflow crowd in a 90-minute session at the meeting. Although it is likely in close-to-final form, the draft still needs sign-offs by the full task force of about 40 people, said the task force convener, Dr. Josef S. Smolen, professor of medicine and chairman of rheumatology at the Medical University of Vienna. The final version of the guidelines will be published soon, Dr. Smolen said.
Although methotrexate is at the top of the treatment hierarchy, it's on a short leash, noted Dr. Smolen. The second of the task force's 15 major recommendations says that treatment aims to produce “remission or low disease activity as soon as possible in every patient.” As long as this goal is not achieved, the adjustment of treatment “should be done by frequent and strict monitoring.” What this means is that if methotrexate alone doesn't produce a good outcome by about 3 months, then the recommendations endorse adding something to methotrexate, he said in an interview.
The recommendations also relegated biologic agents to the niche category of patients with poor-prognosis factors, such as positivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody, early erosive disease, rapidly progressing disease, or high disease activity. Cost is the major factor limiting biologic DMARDs to just these patients.
“There is a strong opinion” among the task force members that only poor-prognosis patients should receive biologic DMARDs, “because patients without a poor prognosis will do well on synthetic DMARDs,” Dr. Landewé said in the interview. “The cost-effectiveness analysis clearly shows that [biologic DMARDs] are not cost effective. Nonetheless, there is a subgroup of patients who benefit from the combination” of methotrexate and a biologic.
If circumstances warrant a biologic DMARD, current practice would start with a tumor necrosis factor inhibitor (such as etanercept, infliximab, or adalimumab) along with methotrexate, according to Dr. Landewé.
“It's a value decision. You need to balance improvements in outcomes against cost,” commented Dr. Paul Emery, arc professor of rheumatology at the University of Leeds (England), EULAR president, and chairman of the recommendations session at the meeting. (Dr. Emery is not a member of the recommendations task force.) “The recommendations allow biologics, especially in poor-prognosis patients, where the benefit is greatest,” he said in an interview.
On this point, the EULAR recommendations are consistent with the most recent, major RA treatment recommendations that were issued by the American College of Rheumatology (Arthritis Rheum. 2008;59:762-84). The ACR recommendations call for using biologic DMARDs in patients with highly active disease and poor prognosis who have no cost or insurance limitations.
A major point on which the ACR and EULAR recommendations diverge is the role for the synthetic DMARD leflunomide. The EULAR guide makes methotrexate the lone top agent, placing leflunomide alongside sulfasalazine and injectable gold as the top DMARD options for patients who are intolerant of or have contraindications for methotrexate. In contrast, the ACR recommendations made leflunomide completely comparable with methotrexate for initial monotherapy.
If only I had known then what this article...and others...make apparent. >>deep sigh<<