Some RA Patients May Be Able to Taper Biologics

Alice Goodman

November 15, 2012

WASHINGTON — Tapering and even stopping treatment with tumor necrosis factor (TNF) inhibitors is feasible in a sizable proportion of patients with rheumatoid arthritis (RA) who are stabilized and in remission.

In a randomized trial reported here at ACR 2012, patients whose TNF inhibitor medications were tapered had no more disease activity or functional impairment than patients who continued on their biologic therapy.

"The study showed that we can reduce the number of injections of TNF blockers if patients are in remission for at least 6 months. However, there was an increased risk of flare in the tapered group; we put those patients back on the last treatment schedule they were on before the flare," said lead author Bruno Fautrel, MD, PhD, from the University of Paris Medical Center in France.

"This study is relevant for the burden of treatment for RA patients and the economic burden to society. These drugs are expensive. If we can taper the intervals and use less drug, we can reduce the cost and possibly reduce the risk of infection and lymphoma," Dr. Fautrel said.

The randomized controlled trial was sponsored by the Ministry of Health in France. It involved 137 patients with RA in remission for at least 6 months who were being treated with subcutaneous injections of TNF blockers.

Patients were randomized to receive continued treatment with full-dose etanercept or adalimumab for the approved time intervals (the maintenance group) or tapered treatment in which intervals between full-dose injections increased by 50% every 3 months and completely stopped by the fourth interval.

At any point, if there was evidence of increased disease activity or worsened physical function reflected by the disease activity score (DAS28), patients were moved back to the previous dose interval. The primary end point of disease activity, DAS28, was assessed every 3 months during the 18-month study.

"The stepped-down strategy allowed patients to remain at a low level of disease activity," Dr. Fautrel noted.

At 18 months, DAS28 was 2.7 in the tapered group and 2.1 in the maintenance group; this difference was not statistically different. Health Assessment Questionnaire results were similar between the 2 groups.

At 18 months, 16% of patients in the tapered group had completely stopped their biologic therapy and 70% were able to taper treatment with longer intervals between subcutaneous injections. However, 15% were unable to stop or taper treatment.

The risk for flare increased in both groups, but was higher in the tapered group than in the maintenance group (81% vs 56%; P = .0009).

Dr. Fautrel and his colleagues plan to analyze the data further to determine whether patients who experienced more flares had increased structural damage. Results should be ready for presentation at the 2013 EULAR meeting. "We hypothesize that there will be no difference between the groups in structural damage," he said during his presentation.

Kelly Weselman, MD, a rheumatologist at WellStar Rheumatology in Atlanta, Georgia, said that the analysis of structural damage in the tapered group will be important. Although the number of patients in this study was small, Dr. Weselman said the results are intriguing. She added that if therapy can be tapered, there are obvious benefits for patients and for cost.

"It would be good to know what the cutoff minimal dose of these biologic therapies is; that is, the minimal dose we could use over time," she said.

Dr. Fautrel reports financial ties with Abbott, Bristol-Myers Squibb, MundiPharma, Pfizer, Roche, and UCB. Dr. Weselman reports participating in the Sunstone Study, funded by Genentech, for the postmarketing surveillance of rituximab in RA patients.

ACR 2012: Abstract L7. Presented November 13, 2012.