Managing Remission Using TNF Inhibitors or Maintenance Therapy

Washington, DC—For some patients with rheumatoid arthritis (RA) in clinical remission, tapering the dose of tumor necrosis factor (TNF) inhibitors used for maintenance therapy or extending the time between doses can be done without significantly increasing disease activity or impairing joint function, according to results of a study presented at the ACR meeting.

According to Bruno Fautrel, MD, the study’s lead author and a rheumatologist at the University of Paris Medical Center in France, the use of maintenance therapy for ongoing treatment of patients with RA who achieve disease remission remains debated particularly with the availability of disease-modifying antirheumatic drugs (DMARDs) that, although effective, also carry safety and cost concerns.

To examine the risk/benefit balance of using DMARDs over the long term in RA patients in clinical remission, Dr. Fautrel and colleagues conducted an 18-month randomized trial of patients with RA who were in stable remission (defined as Disease Activity Score 28 [DAS28] score <2.6 for at least 6 months) and receiving treatment with the anti-TNF agent etanercept or adalimumab for 1 year either alone or in combination with other drugs. All patients included in the trial were ≥18 years of age and had no progression of structural damage on imaging. Patients were allowed treatment with prednisone at a daily dose of 5 mg/d.

The STRASS (Spacing of TNF-Blocker Injections in Rheumatoid Arthritis Study) trial compared 2 different treatment strategies for the management of remission in this patient population by randomizing the patients to either a DAS28-driven step-down strategy with progressive spacing of TNF-blocker injections (S arm) or maintenance of therapy at full dose (M arm). In the S arm, the interval between 2 subcutaneous injections was increased by 50% every 3 months up to a full stop at the fourth step. Dose tapering was suspended or reversed to the previous interval based on DAS28 level in patients whose DAS28 remission was not maintained.

A total of 137 patients were included in the study, 64 were randomized to the S arm and 73 to the M arm. For both groups, mean age was 55 years, and most were female (78%). Baseline characteristics of RA disease included mean duration of disease of 9.5 years, DAS28 of 1.8, DAS44 of 1.0, Health Assessment Questionnaire 0.4, and number of previous DMARDs was 2.7.

Patients were followed for 3 months for up to 18 months. At 18 months, 15% of the patients in the S arm had completely stopped anti-TNF treatment and 67% had tapered treatment, while the remaining 18% were unable to taper treatment and remained at the initial injection interval.

The study was unable to demonstrate the equivalence between the 2 treatment arms, which was the primary end point of the study. However, no difference in disease activity at 18 months was seen between the S arm and M arm as demonstrated by DAS28 (2.7 vs 2.2, respectively; P=.22), DAS44 (1.6 vs 1.4; P=.58), and functional status (P=.88). In addition, no difference in safety was seen between the groups.

Because of dose tapering, however, patients in the S arm had a significant increase in relapse compared with those in the M arm (81% vs 56%, P=.0009); the S arm also had a significant increase in RA flares (P<.0001).

According to Dr. Fautrel, a limitation of the study was the likelihood that the study was underpowered because of the lower than expected number of patients included in the study. The study was designed to include 250 patients, 125 in each arm. However, only 144 patients were recruited and of those, only 137 were evaluable.

Overall, the study showed that tapering anti-TNF therapy was feasible in 82% of patients without a significant increase in disease activity or functional impairment. Dr. Fautrel said a follow-up study is now being conducted to examine the impact of tapering treatment as measured by x-ray of structural damage.