By Wayne Kuznar
Chicago, IL—More than 25% of patients with rheumatoid arthritis (RA) who are started on methotrexate (Trexall, Rheumatrex) alone achieve clinical remission at week 24, and the remission is durable out to 2 years, said James R. O’Dell, MD, Professor of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, at the 2011 meeting of the American College of Rheumatology.
In the Treatment of Early Aggressive RA (TEAR) trial, 755 patients were randomized to 1 of 4 treatment arms. One arm received methotrexate and etanercept (Enbrel) from the outset, and a second arm was assigned to methotrexate, sulfasalazine (Azulfidine), and hydroxychloroquine (Plaquenil; triple therapy) from the outset. In the other 2 arms, patients were initiated on methotrexate alone and stepped up to either etanercept or triple therapy at week 24 if they could not achieve a Disease Activity Score in 28 joints (DAS28) of ≤3.2 on methotrexate monotherapy.
To be included, patients had to have active, poor-prognosis RA, which is defined as rheumatoid factor–positive disease or anticyclic citrullinated peptide–positive disease, or the presence of at least 2 erosions. Disease duration had to be <3 years and only limited prior exposure to disease-modifying antirheumatic drug therapy was allowed. Oral prednisone was permitted at ≤10 mg/day.
The mean disease duration was 3.6 months, and patients’ mean DAS28 at baseline was 5.8. Patients in the methotrexate monotherapy arm had dose escalation (from a starting dose of 10 mg) to 15 mg and to 20 mg at weeks 6 and 12, respectively, if they had a single tender or swollen joint at either time point.
In the primary analysis, at 24 weeks, patients assigned to combination treatment had clinically superior responses on DAS28, but the difference was lost by 36 weeks after nonresponders stepped up to double or triple therapy.
Radiographic outcomes between the 4 treatment arms from treatment initiation to week 102 were nearly identical. “There was no radiographic penalty for waiting to make the decision clinically [to step up after initial methotrexate therapy],” said Dr O’Dell.
In the group assigned to methotrexate monotherapy, 72% had a DAS28 >3.2 and stepped up to either etanercept or sulfasalazine/hydroxychloroquine, whereas 28% had low disease activity (DAS28 ≤3.2) and remained on methotrexate monotherapy.
Patients who stepped up had significantly more tender and swollen joints and a higher mean DAS28 score than those who did not require step-up therapy.
Of patients receiving methotrexate alone, 28% achieved DAS28 remission at week 24, and these responders maintained a durable response to 2 years. Of patients receiving methotrexate alone, 57% achieved a meaningful clinical response, which was defined as a DAS28 improvement of at least 1.2 points by week 24.
There was an immediate advantage to using all drugs together when measuring the outcome (DAS28 remission) at 24 weeks, “but if you measure outcome between 1 and 2 years, there is no advantage clinically to doing that, and you should make the decision to step up to these other therapies based on clinical outcome,” he said.
“The methotrexate responders do not progress radiographically at 2 years,” he said. Mean radiographic progression in radiographic Sharp scores over 2 years was 0.15 in those staying on methotrexate alone compared with 1.22 in those who received step-up therapy and 1.01 in those assigned to immediate double or triple therapy.