PHILADELPHIA, Pennsylvania—Early rheumatoid arthritis (RA) responds as well to initial methotrexate (MTX) plus 2 more conventional DMARDs if needed after 6 months to bring disease under control as to MTX plus a more expensive anti-TNF inhibitor, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Philadelphia, PA.1

”Patients initially receiving immediate MTX + etanercept or immediate triple-DMARDs were significantly more likely to achieve an ACR 20/50/70 response at 6 months than those randomized to step-up arms.”—Larry W. Moreland, MD
Larry W. Moreland, MD, Chief of the University of Pittsburgh's Rheumatology & Clinical Immunology Center, and a team of other top researchers set out to answer a question not previously addressed in a head-to-head trial: how would triple DMARD (methotrexate [MTX], sulfasalazine, hydroxychloroquine) therapy compare to MTX plus anti-TNF therapy (etanercept) for treatment of early RA?

They set up the TEAR investigator-initiated, multi-center, randomized trial to answer this question, and also to determine the relative benefit of a strategy of either combination versus MTX monotherapy with step-up after 6 months.

The researchers found that at 6 months, either combination therapy approach led to better responses than initial treatment with methotrexate alone. However, during the second year of this trial, they found no differences in the average levels of DAS28 between patients randomized to etanercept or triple DMARD therapy, regardless of whether they received immediate combination treatment or initial therapy with methotrexate with a step-up.

The researchers enrolled 755 participants to compare immediate (I) versus step-up (S) strategy with MTX, etanercept (E) and triple DMARD (T) in 4 arms: immediate MTX + E (IE) or triple therapy (IT); step-up from MTX to MTX+E (SE) or to T (ST).

In the SE/ST part of the study, patients were blindly stepped up to triple DMARD therapy or to MTX + E if DAS28 ≥ 3.2 at 6 months of MTX. All patients were MTX-naive at entry. The mean DAS at entry was 5.8.

The primary endpoint was mean DAS28 from weeks 48-102. Other endpoints: ACR 20, 50, 70; discontinuation for lack of efficacy, DAS28 remission, quality of life, and radiographic progression.

Dr. Moreland reported, “During the second year of treatment, patients randomized to step-up arms had clinical responses that were not statistically different than those who received immediate combination therapy, regardless of treatment arm (p-values: I vs S: 0.95, E vs T: 0.23). There were significant differences in the outcome of ACR response at 6 months between treatment arms: patients initially receiving immediate MTX + etanercept or immediate triple-DMARDs were significantly more likely to achieve an ACR 20/50/70 response at 6 months than those randomized to step-up arms (all p < 0.0001), regardless of treatment (E vs T).”

The investigators concluded, “Initial use of MTX monotherapy with the addition of SSZ/HCQ or etanercept, if necessary after 6 months, is a reasonable therapeutic strategy for early RA.”

Reference
1. Moreland LW, O'Dell JR, Paulus, HM, et al. TEAR: Treatment of Early Aggressive Ra; A Randomized, Double-Blind, 2-Year Trial Comparing Immediate Triple DMARD Versus MTX Plus Etanercept to Step-up From Initial MTX Monotherapy. Presented at the 2009 American College of Rheumatology Annual Meeting, Philadelphia, October 20, 2009. Presentation no. 1895.