Reducing the Dose of Anti-TNF Agents Appears Feasible in Spondyloarthritis

Recently, a study sought to determine whether dose reductions of anti–tumor necrosis factor (anti-TNF) therapies are possible for long-term treatment of spondyloarthritis, and found that a reduced dose is noninferior to a full dose in patients in sustained clinical remission.
The Center for Biosimilars Staff
March 23, 2019
Anti–tumor necrosis factor (anti-TNF) therapies are often efficacious in treating spondyloarthritis, but the optimal duration and dose for long-term treatment are not yet clear; currently, doses recommended for acute and chronic disease are the same. In addition to the high cost of these drugs and their potential to increase the risk of serious infections, it is not yet known whether chronic use may increase malignancies or demyelinating diseases. Recently, a study sought to determine whether dose reductions are possible for long-term treatment of spondyloarthritis, and found that a reduced dose is noninferior to a full dose in patients in sustained clinical remission.

The prospective, multicenter, randomized open-label trial was conducted at 22 studies in Spain. Patients were eligible to enroll if they were taking the recommended dose of infliximab, adalimumab, etanercept, or golimumab and had been in clinical remission for 6 months or more.

The 126 enrolled patients were randomized to receive either the full recommended dose of their anti-TNF agent (n = 63) or a reduced dose (n = 63), according to an agreed-upon protocol. For example, in those taking adalimumab, patients with standard dosing received 40 mg every 2 weeks, while the reduced dose group received 40 mg every 3 weeks. In those taking infliximab, the full-dose group received 5 mg per kg every 6 to 8 weeks, while the reduced-dose group received 3 mg per kg every 8 weeks. The primary end point was the proportion of patients with low disease activity (LDA) at 1 year.

The study found that the proportion of patients with LDA at 1 year was 83.9% (95% CI, 64.8%-102.7%) in the full-dose arm and 81.3% (95% CI, 62.8%-99.8%) in the reduced-dose arm. The absolute difference in LDA at 1 year in the per-protocol set population was –2.5% (95% CI, –16.6 to 11.7%). The lower bound for the CI in the control arm was greater than 60%, fulfilling prespecified validation criteria.

The percentage of patients in clinical remission, a key secondary end point, at 1 year was 83.7% (95% CI, 64.7%-102.7%) in the full-dose arm and 78.2% (95% CI, 59.7%-96.8%) in the reduced-dose arm, with absolute differences between treatment groups of −5.5% (95% CI, −20.6% to 9.7%) (P = .480) 

Serious treatment-related adverse events or infections were reported in 11.3% of the full-dose group, and in 3.3% of the reduced-dose group (P = .164). Treatment was discontinued by 9.7% of the full-dose group and 21.3% of the reduced-dose group (P = .086).

“This trial has shown that a dose-reduction strategy may be non-inferior to full-dose treatment in patients with AS in persistent clinical remission with [anti-TNF agents], in terms of maintenance of LDA after 1 year,” write the investigators.

Reference
Gratacós J, Pontes C, Juanola X, et al. Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondylarthrosis. Arthritis Res Ther. 2019;21(1):11. doi: 10.1186/s13075-018-1772-z.

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