Conference Coverage
BOSTON – Aggressive treatment of rheumatoid arthritis patients aimed at achieving Disease Activity Scores of 2.4 or less was associated with mortality rates that were not significantly different from those seen in the general population, based on the results of a 10-year Dutch study.
Irrespective of the treatment regimen, keeping the DAS (Disease Activity Score) at 2.4 or below is associated with lower inflammation, according to Dr. Iris Markusse of Leiden University Medical Center. “Historically, mortality risk in RA was significantly increased when inflammation was not as effectively suppressed ... [but with intensified treatment] inflammation can be so well controlled that it no longer affects overall survival.”
In the Behandel Strategieen (BeST) study, 508 patients with recent active-onset RA were randomized to one of four treatment approaches. Patients received either sequential monotherapy with methotrexate, step-up therapy with methotrexate, methotrexate plus sulfasalazine and prednisone, or methotrexate and infliximab. For all patients, the treatment target was a DAS of 2.4 or less, and follow-up occurred at 3-month intervals.
Patients who started on methotrexate monotherapy and had a DAS exceeding 2.4 received the next step in therapy, which included adding or switching to other therapies as needed. Conversely, if low disease activity was seen for at least 6 consecutive months, combination therapy was tapered to maintenance monotherapy. After the third year of the trial, patients who had at least 6 consecutive months on maintenance monotherapy had to stop that drug as well.
Over the course of the study, 80% of participants had low disease activity, 45% were in remission, and 15% were in drug-free remission, she reported at a press conference during the annual meeting of the American College of Rheumatology.
Of the 508 patients, 72 died at a mean age of 75 years; the deaths occurred in 16 of 126 patients on methotrexate monotherapy, 15 of 121 on step-up methotrexate, 21 of 133 on methotrexate plus sulfasalazine and prednisone, and 20 of 128 on methotrexate and infliximab. Based on the general Dutch population, 62 deaths would have been expected.
While mortality risk was not significantly different among the treatment arms; mortality risk was higher for patients who were older at baseline, male, smokers, and those with poorer scores on a baseline health assessment questionnaire. The most significant risk factor was smoking at baseline (hazard ratio, 5.19; 95% confidence interval, 3.08-8.75).
Encouraging patients to quit smoking might be effective for reducing mortality, she added.
Dr. Markusse declared having no relevant financial disclosures. Funding for the study included a government grant from the Dutch College of Health Insurance Companies, with additional funding from Schering-Plough/MSD and Centocor/Janssen.