Early Treatment Benefits Patients with Rheumatoid Arthritis

Newswise — Early, aggressive treatment may be most beneficial, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Diego, California.

The BeSt study is a multi-center, randomized controlled trial designed to evaluate the effectiveness of four different treatment strategies for patients with early, active rheumatoid arthritis who had not yet received DMARD therapy. A total of 508 patients with active rheumatoid arthritis whose symptoms were in place for two years or less were randomized into one of four treatment groups: sequential monotherapy (group one: 126 patients); step-up combination therapy (group two: 121 patients); initial combination therapy with a tapered high dose prednisone (group three: 133 patients); and initial combination therapy with methotrexate and infliximab (group four: 128 patients). Patients were frequently seen and their disease activity was assessed. If the target of low disease activity was not reached, treatment was changed according to an algorithm specific for each of the 4 groups. Researchers will present three sets of findings during the ACR annual meeting based on the BeSt study.

In the first set of findings (presentation #1865), researchers focused on the treatment strategy that should be pursued after patients failed on methotrexate (generally the first line of treatment for early rheumatoid arthritis). After six months of treatment in one of the four treatment groups, 44% of patients in groups one and two did not respond to methotrexate monotherapy. Switching to another DMARD, or adding another DMARD for combination therapy also did not yield acceptable percentages of patients achieving acceptable DAS scores. However, researchers did find that the majority of patients failing on multiple DMARDs still respond to a combination therapy of methotrexate and a TNF inhibitor (infliximab).

In the second set of findings (presentation #1467), researchers set out to determine if the rapid clinical improvement with initiation combination therapy with either prednisone or infliximab were reflected by patients' self-assessed outcomes for pain, disease activity (e.g., prevalence and severity of symptoms) and performance. All patients completed the MACTAR questionnaire, an instrument used to assess improvement in physical disability (functional outcome), as well as scores for pain, overall health and disease activity (known as VAS scores) every visit during the first year of follow-up. Baseline characteristics were comparable for all groups at the beginning of the study. Functional outcomes improved more rapidly in groups three and four. After one year, differences among the four groups were smaller, but patients in group four (methotrexate plus TNF inhibitor) scored significantly better than patients in group one. Patients' scores for pain, overall health and disease activity were significantly lower than baseline in all four groups after one year. In all groups, treatment resulted in substantial improvement in functional ability and self-assessed VAS scores; however, patients initially treated with combination therapy showed more rapid improvement than patients in the mono- or step-up therapy groups. In the third set of findings (presentation #843), researchers set out to identify patients with osteoporosis and evaluate possible risk factors for osteoporosis in people with early, active rheumatoid arthritis. Baseline bone mineral density measurements of the lumbar spine and total hip were performed by DXA in 342 patients (240 women and 102 men with a mean age of 54.6 years). Radiological damage of the hands and feet was also assessed. In this group, the clinical, demographic and radiological characteristics of patients that had osteoporosis and those that did not were compared and assessed. Osteoporosis was found more often in patients with a positive rheumatoid factor, an older age, in postmenopausal women and in those with low body mass index " the last three classic risk factors. However, researchers did note that the duration of rheumatoid arthritis or its activity did not correlate with osteoporosis.

"With various outcome-targeted treatment strategies using tight disease control, more than 40% of patients with early rheumatoid arthritis can be brought into remission, and the large majority in a state of low disease activity without progressive joint destruction," said Ferdinand C. Breedveld, MD, and lead investigator in the BeSt study. "Of the four treatment strategies compared (sequential monotherapy, step up, initial combination therapy with corticosteroids and initial therapy with TNF antagonists), the last two reach an earlier therapeutic success with respect to DAS, HAQ and remission as well as a more complete inhibition of radiographic progression compared to the first two. Given the non-significant outcome of the four groups with respect to disease activity levels after two years, the conclusion at this moment is that all strategies are successful as long as the treatment follows the decision scheme of tight disease control, with every-three-months changes of therapy if the goal is not reached. Also in strategies one, two and three, TNF antagonists are needed at the 10 to 28% level within two years to reach this goal."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.