A chronic and potentially crippling inflammatory disorder, rheumatoid arthritis (RA) progressively wears away the cartilage and bone.

Joint erosions are routinely seen within 6 months of RA’s onset, and occur more rapidly earlier in the course of the disease. Moderate disability within 2 years of diagnosis is not uncommon. While conventional DMARD (disease-modifying antirheumatic drug) therapies have been shown to slow joint destruction, they are powerless to stop RA’s progression or reverse joint damage.

As researchers widely agree, early intervention offers RA patients the most promise for preventing irreversible joint damage and avoiding severe disability. In addition to early treatment, combination treatment, with DMARDs as well as with biologic agents, has been shown to yield more favorable outcomes than a single treatment.

The January 2006 issue of Arthritis & Rheumatism presents the first study to compare the effectiveness of DMARD therapy alone, anti-TNF (tumor necrosis factor) therapy alone, and a combination of DMARD and anti-TNF therapy. The compelling results affirm the long-term benefits of early combination therapy for women and men afflicted with aggressive RA.

The study was sponsored by Abbott Laboratories and conducted at 133 sites throughout North America, Europe, and Australia. It focused on patients with active RA for less than 3 years who had never been treated with the DMARD methotrexate (MTX). A total of 799 patients were enrolled in the study. The majority were women. The mean age was 52 years. 57 percent of the participants had RA for 6 months or less. The subjects were randomly divided into one of 3 treatment groups: MTX, in pill form, starting with 20 milligrams weekly; the anti-TNF adalimumab, administered by injection, starting with 40 milligrams every other week; and a combination of adalimumab plus MTX, starting at the same dosage levels as the single treatment groups. For all groups, treatment effectiveness was thoroughly evaluated after 6 months, 1 year, and 2 years. 539 of the participants completed 2 years of their assigned treatment.

In all outcome measured, the combination of treatments was clinically and statistically superior to both adalimumab and MTX alone. Following 1 year of treatment, 62 percent of patients in the combination therapy group had 50 percent improvement in disease symptoms, according to the standard American College of Rheumatology criteria, compared with 41 percent of patients in the adalimumab only group and 46 percent of patients in the MTX only group. In addition, there was significantly less radiographic disease progression at 6 months, 1 year, and 2 years among patients in the combination treatment group than among those in either single treatment group. What’s more, after 2 years of treatment, nearly half the patients in the combination therapy group exhibited a major clinical remission, rates approximately twice those found among patients receiving either single therapy.

The combination of DMARD and anti-TFN therapy proved safe and well tolerated by patients. The incidence of infections and other adverse events were low and comparable in all 3 treatment groups. What’s more, increasing the dosages of either adalimumab or MTX alone failed to yield the improvements experienced by patients receiving both treatments in relatively low dosages.

As spokesperson George T. Spencer-Green points out, the study’s participants had an unusually high level of radiographic damage present at baseline for their average disease duration of under one year. Early RA patients with milder forms of the disease may benefit from early DMARD therapy under a clinician’s supervision. “For the patient with early, aggressive and erosive, RA,” he notes, “treatment with combination therapy is superior to treatment with MTX alone.”

http://www.interscience.wiley.com/journal/arthritis