Rheumatoid arthritis patients with low disease activity are less likely to flare if they continue their treatment with etanercept and methotrexate, even if they take half the dose of the anti-TNF agent, a double-blind, randomized trial showed.

The researchers conducting the trial, called DOSERA (Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State), led by Dr. Ronald F. van Vollenhoven of the Karolinska Institute in Stockholm, reported that the proportion of patients who successfully maintained low disease activity was significantly higher with etanercept 50 mg (52%; P = .007) and 25 mg (44%; P = .044), compared with placebo (13%). They defined failure as an increase in 28-joint Disease Activity Score (DAS28) of 0.6 or more and an absolute value of greater than 3.2 or disease progression as determined by investigator/patient assessment.

According to the authors, the results are important because, theoretically, they represent the first controlled demonstration that an induction maintenance strategy can be applied in some patients with established RA for whom the use of an anti-TNF agent is clinically necessary.

From a clinical practice point of view, the results also suggest that it might be possible to reduce dosages in some patients while maintaining the same favorable disease state.

“However, a full assessment of this possibility would require considerably more robust data in a larger population on the full clinical as well as radiographic effects, both short term and long term,” Dr. van Vollenhoven and his associates wrote, adding that “it is not possible to know whether these data would apply equally to other anti-TNF agents.”

Median time to flare was significantly shorter for patients taking methotrexate plus placebo at 6 weeks, compared with etanercept 50 mg at 48 weeks (P = .001) and 25 mg at 36 weeks (P < .001), the researchers reported (Ann. Rheum. Dis. 2015 April 14 [doi:10.1136/annrheumdis-2014-205726]).

Most patients (91%) who flared and then restarted open-label etanercept 50 mg/week responded promptly, with median times until low disease activity or remission being 6.0 weeks for the 50-mg group, 5.9 weeks for the 25-mg group, and 3.9 weeks for the placebo group.

Adverse events were consistent with the patient population and known side effects of etanercept and methotrexate.

The study had several weaknesses, including its limited size and associated wide confidence intervals, the researchers noted, resulting in “uncertainty regarding the comparison of the clinical efficacies of full-dose and reduced-dose [etanercept] continuation.”

Etanercept also is not approved at doses other than 50 mg for the treatment of adults with RA. A dose reduction was therefore not supported by the product label and also entails some practical difficulties, Dr. van Vollenhoven and his associates added.

The study included 91 patients who had been receiving etanercept, 50 mg/week, plus methotrexate, 7.5-25 mg/week for at least 14 months and had a DAS28 score of 3.2 or lower.

After an 8-week run-in phase, 73 patients were randomized in a double-blind design to etanercept 50 mg/week plus methotrexate, etanercept 25 mg/week plus methotrexate, or placebo plus methotrexate for 48 weeks.

The study was sponsored by Wyeth, which was acquired by Pfizer. The investigators designed the study protocol prior to the agreement by Wyeth to support the study. Some of the authors reported receiving research support and/or honoraria from numerous pharmaceutical companies or serving as consultants to them. Several reported being employees of Wyeth or Pfizer at the time of the study.