Step-Down Strategy Is Feasible in Many Patients with Rheumatoid Arthritis Who Achieve Remission

VBCR - February 2013, Volume 2, No 1 - Arthritis

By Wayne Kuznar

Washington, DC—Tapering the doses of anti–tumor necrosis factor (TNF) drugs can be done successfully in some patients with rheumatoid arthritis (RA) who achieve remission. A step-down strategy was possible in >80% of patients without significant increases in disease activity or functional impairment, although relapses occurred more frequently than in those who remained using a full regimen, said Bruno Fautrel, MD, PhD, a professor at the University of Paris Medical Center, at the 2012 meeting of the American College of Rheumatology.

Dr Fautrel and his colleagues conducted an 18-month equivalence randomized controlled PROBE (Prospective Open Blinded Endpoint) trial in 137 established patients with RA who received etanercept (Enbrel) or ada­limumab (Humira) and were in stable remission by the 28-joint Disease Activity Score (DAS28) criteria (DAS28 ≤2.6).

“A lot of effort has been dedicated to the development of new treatments for RA, leading to a substantial increase in RA costs. Nowadays, remission is achievable and treatment tapering needs to be considered and assessed,” said Dr Fautrel.

The goal of the study was to compare the impact of a step-down strategy based on the progressive spacing of anti-TNF injections with a strategy that maintained the therapy at full doses at the approved time intervals. The study was powered to demonstrate noninferiority of the step-down arm.

All of the patients were using etanercept or adalimumab for 1 year, as monotherapy or in combination with other agents. The patients were permitted to take ≤5 mg of prednisone daily. The mean duration of RA was 9.5 years, and the mean DAS28 was 1.8. The mean number of previous disease-modifying antirheumatic drugs taken per patient was 2.7. Eighty-eight percent of the patients had erosive disease.

In the step-down group, the time between the 2 injections was expanded by 50% every 3 months up to a complete stop by the fourth interval. If DAS28 remission was not maintained, the full regimen was reestablished. The primary end point was disease activity based on DAS28 measures performed every 3 months for 18 months.

After 18 months, 82% of the patients in the step-down arm were able to space out or stop their anti-TNF injections, without significant increases in either disease activity on the DAS28 or in functional impairment. Another 15% of the patients were able to stop therapy completely, and 67% were able to taper off their medication. The remaining 18% of the patients were unable to taper their treatment and remained at the initial injection interval.

“However, we failed to demonstrate the equivalence between the 2 strategies [P = .6] and, due to the step-down strategy, a relapse occurred more frequently in the step-down than in the full regimen arm—81% versus 56%,” said Dr Fautrel. “Although we failed to demonstrate the equivalence between the 2 strategies, the spacing strategy did not result in a significant increase in disease activity or functional impairment.”

The impact of the spacing strategy on x-ray structural damage is currently being analyzed.

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