Treat-to-target approach prevents increased mortality risk in rheumatoid arthritis

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Researchers in the Netherlands conducted the Behandel Strategieen (BeSt) Study, including 508 patients with recent active-onset RA from March 2000 to August 2002. They compared survival rates of these patients with that of the general Dutch population and sought to define risk factors for mortality during the 10-year duration of the study. "The BeSt study was set up as a four armed comparison study, aiming to find which is the optimal order of use of available anti-rheumatic therapies, with outcomes improvement of functional ability and prevention of radiological damage," said C.F. Allaart, MD of the Leiden University Medical Center and a lead author of the study.

The study's arms mainly differed in initial treatment strategies: arms one and two started with a single anti-rheumatic drug, methotrexate, (and switched to, or added, other therapies if necessary) while arms three and four started with a combination of methotrexate with either sulfasalazine plus prednisone or TNF blocker infliximab, combinations that would be tapered to monotherapy if the clinical response was sufficient.

Response to treatment was measured every three months using a Disease Activity Score (DAS) target of 2.4 or lower. If DAS was higher than 2.4, the researchers took the next treatment step in the respective arm. If low disease activity was achieved for at least six consecutive months, medication was tapered to a monotherapy maintenance dose. From year three, the protocol was extended with the requirement that patients who had achieved at least six consecutive months on monotherapy maintenance dose had to stop that last drug too. Across time, some 80 percent of participating patients were in low disease activity, 45 percent were in remission and 15 percent in drug-free remission.

During the 10-year study, 72 of the 508 RA patients died at a mean age of 75 years. The different treatment strategies used to achieve the DAS goal did not result in a difference in survival rates. Compared with mortality rates in the general population, 62 deaths would have been expected, resulting in a standard mortality ratio of 1.16 for the RA patient population, with a 95-percent confidence interval of 0.92 to 1.46, so the difference was not statistically significant.

Several risk factors were associated with higher mortality: higher age, male gender, smoking and worse functional ability scored on the Health Assessment Questionnaire. The researchers concluded that in RA patients treated at a target of low disease activity, the mortality rate is similar to that in the general population. Because the treatment was targeted to keep the patient at DAS ≤2.4, inflammation was better controlled than in earlier cohorts where there was increased mortality. The medication used to treat to target does not increase mortality, they concluded.

Rheumatologists might reduce mortality by treating all RA patients to a target of low disease activity and encouraging RA patients to stop smoking, the study's authors further concluded.

"Historically, mortality risk in RA was significantly increased when inflammation was not as effectively suppressed as for instance in the BeSt cohort to date. RA was a deadly disease," said Dr. Allaart. "But with earlier treatment and targeted treatment, where medication is intensified until low disease activity is achieved and maintained (and this appears independent of treatment strategy or the order in which medication is used), inflammation can be so well controlled that it no longer affects overall survival."