Triple DMARD Treatment More Effective than Monotherapy in New RA Cases

Although methotrexate with or without glucocorticoids (GCs) is commonly used as a first-line treatment in rheumatoid arthritis (RA), results from a study presented at the American College of Rheumatology 2013 Annual Meeting in San Diego show that combining the medication with two other traditional disease-modifying anti-rheumatic drugs (DMARDs) produces better outcomes in newly-diagnosed RA patients — despite current guidelines against the triple therapy’s administration in those patients.

“There is still debate on the most appropriate initial treatment regimen in patients with newly-diagnosed RA, (but) the most important discussion herein is that of initial methotrexate monotherapy versus a combination of DMARDs,” Pascal de Jong, PhD, of the Department of Internal Medicine at Erasmus University Medical Center, explained in a statement. “Therefore, we investigated in our [Treatment in the Rotterdam Early Arthritis Cohort (tREACH)] trial if triple DMARD therapy was better than methotrexate monotherapy independent of corticosteroids at treating RA symptoms.”

For their single-blinded tREACH clinical trial, de Jong and researchers across the Netherlands randomized 281 recent-onset RA patients with a high probability of progressing to persistent RA to one of three treatment groups:

• 25 mg methotrexate per week, 2 g sulfasalazine per day, and 400 mg hydroxycholorquine per day, in addition to one 120 mg dose of intramuscular GC depomedrol
• The same triple DMARD therapy with a tapered dose of oral GCs starting at 15 mg
• 25 mg methotrexate per week with the same tapered GC dose

According to the investigators, participants were given various dosage forms and strengths of GCs in addition to their methotrexate monotherapy or triple DMARD regimen in order to fulfill the study’s secondary aim of comparing the efficacies of oral GCs and a single dose of intramuscular GCs, which are two current methods of using GCs as bridging therapy in early-stage RA.

After measuring disease activity scores and collecting health assessment data every 3 months — as well as examining radiographic RA progression, medication usage, and adverse events after 12 months of therapy — the study authors wrote that “over time, disease activity and functional ability were respectively lower in patients with triple DMARD therapy compared with methotrexate monotherapy.”

Additionally, the researchers found that “after 3 months, less treatment failure occurred in the triple DMARD therapy groups, resulting in the prescriptions of 50 percent fewer biologicals, (and) this difference remained over time.” However, no significant differences were seen between the two GC bridging therapy approaches.

Comparing one-year radiographic results among the three patient groups, the authors determined that 15% of the triple therapy with intramuscular GC group, 30% of the triple therapy with tapered oral GC group, and 18% of the methotrexate monotherapy group displayed radiographic progression of RA.

Thus, the authors concluded that triple DMARD therapy is superior to methotrexate monotherapy in newly-diagnosed RA patients, even after one full year of treatment. In addition, de Jong recommended “initial triple DMARD therapy over methotrexate monotherapy as the first choice in newly-diagnosed RA patients, because treatment goals are attained faster and maintained with 40% fewer biological” drug prescriptions.