Patients with rheumatoid arthritis (RA) who receive the anti-tumor necrosis factor (TNF) therapy etanercept (Enbrel) early in their disease show a more marked reduction in disability than those with established RA who receive the therapy, according to findings published in the most recent issue of Journal of Rheumatology.

The investigators particularly saw these differences in Health Assessment Questionnaire (HAQ) scores. "We found that etanercept significantly decreased disability in both early and later stages of RA, most likely by reducing inflammatory disease activity," the authors wrote. "However, patients with recent-onset RA responded with a greater magnitude of HAQ improvement than did those with established RA." The study was funded by Immunex Corporation, a subsidiary of Amgen, which manufactures Enbrel.

"There is a growing body of evidence that with early treatment we can get better results clinically, and perhaps ‘reset' the course of disease in the individual patient," lead author Scott W. Baumgartner, MD, told CiaoMed. "This study shows us a couple of things. First, consistent with other early RA trials, we get better responses in early RA patients. Second, we have a better chance of restoring normal function in the early RA patient than in the later patient if we treat aggressively." Dr. Baumgartner, a rheumatologist, is Medical Director of Clinical Research at the Physicians Clinic of Spokane in Spokane, Wash. He is also Assistant Clinical Professor of Medicine at the University of Washington School of Medicine in Seattle.

The investigative team reviewed the HAQ scores of 2 groups of patients over a 3-year period. One group consisted of 207 methotrexate-naïve patients with recent onset of RA (within the past year), and the other group consisted of 464 patients with established RA (average duration, 12 years) who had not responded to disease-modifying anti-rheumatic drugs (DMARDs).

Although both groups exhibited a sustained and rapid response to etanercept, the HAQ scores showed that the recent-onset group had a more marked decrease in disability, reported the authors, with the differences becoming evident as early as week 2. By the end of the third year, 26 percent of the recent-onset patients had a HAQ score of 0, compared to 14 percent of patients with established RA (P = 0.0095).

"The greater magnitude of improvement, the rapidity of improvement, and the higher percentage of patients achieving a HAQ score of 0 among early-onset patients show the advantages of early intervention," Dr. Baumgartner said. "In the early patient, before significant joint damage has occurred, inflammation is the larger contributor to disability. With early control ... there is a greater probability of restoring normal function." Noting that these findings echo those of others who have studied early intervention with anti-TNF therapies, Dr. Baumgartner said, "We think this is a class effect. This study adds to a growing body of compelling evidence that we can do better for people if we treat earlier with anti-TNF therapies."

In the same issue of Journal of Rheumatology, other researchers reported that patients receiving the anti-TNF agent infliximab (Remicade) may have to increase their doses for efficacy, particularly during the first year of treatment, according to the results of 2 studies evaluating the dosage and rates of increase in infliximab-treated patients with RA. The first study reviewed the charts and infusion records of 394 RA patients from 2 large rheumatology practices in Dallas. The second study surveyed 1324 RA patients using infliximab who participated in a longitudinal study of RA outcomes. In each study patients' doses were increased over the recommended initial dose of 3 mg/kg to an average dose of 5 mg/kg. These increases took place in 61 percent of patients in the first study and in 56 percent of patients in the second study.

According to authors Richard Stern, MD, of the University of Texas Southwest Medical Branch in Dallas, and Frederick Wolfe, MD, of the National Data Bank for Rheumatic Disease in Wichita, Kan, the most common reason for dose increases was insufficient response. They noted that those requiring increased doses had a poorer disease status. Also, patients who received the higher doses exhibited fewer infliximab antibodies and a better response to treatment. "Ideas about infliximab dose and dose interval are changing," noted the authors.

These and other findings reflect the rheumatologic community's increased familiarity with anti-TNF therapies. On August 10, 2004 the FDA approved an expanded indication for adalimumab (Humira, Abbott) to include improvement in physical function for adult patients with moderately to severely active rheumatoid arthritis. The physical function approval was based on a 52-week open-label continuation study of 457 RA patients with inadequate response to methotrexate who were previously enrolled in a double-blind placebo-controlled 52-week lead-in study.

References

Baumgartner SW, et al. Etanercept (EnbrelR) in patients with rheumatoid arthritis with recent onset versus established disease: improvement in disability. J Rheumatol. 2004;31:1532-1537.

Stern R, Wolfe F. Infliximab dose and clinical status: results of 2 studies in 1642 patients with rheumatoid arthritis. J Rheumatol. 2004;31:1538-1545.