medwireNews: Adalimumab-treated rheumatoid arthritis (RA) patients who have serum drug concentrations greater than 8 µg/mL can extend their dosing interval without compromising disease control, the results of a noninferiority trial suggest.
Several factors, including immunogenicity, affect the pharmacokinetics of the tumor necrosis factor inhibitor, giving rise to “a wide range of adalimumab concentrations at the approved dose,” explain Merel l’Ami, from Amsterdam Rheumatology and Immunology Center in the Netherlands, and study co-authors.
“Higher adalimumab concentrations result in better clinical response, but the curve plateaus around 5 μg/mL,” meaning that patients with minimum serum concentrations above this value are “most likely overexposed” to the drug, they add.
In their open-label trial, l’Ami and colleagues randomly assigned patients who had been receiving adalimumab treatment at a dose of 40 mg every other week for at least 28 weeks, and had achieved a trough concentration above 8 µg/mL, to either reduce their treatment frequency to once every 3 weeks (prolongation group) or continue with the same dosing interval (continuation group).
The mean adalimumab concentration was reduced from 10.6 μg/mL at baseline to 6.6 μg/mL at the 28-week follow-up among the 27 patients in the prolongation group, and decreased slightly from 10.4 μg/mL to 9.3 μg/mL for the 27 participants in the continuation group, representing a significant difference between the groups.
Patients in the prolongation group experienced a decrease in mean disease activity score at 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) from 2.0 points at baseline to 1.9 points at week 28, compared with an increase from 1.6 to 2.0 points among those in the continuation group.
These findings translated into a significant 0.44-point difference in the change in DAS28-ESR favoring prolongation of the treatment interval, report the researchers in the Annals of the Rheumatic Diseases.
Adverse events were reported by two patients in the prolongation group and 14 in the continuation group. The most commonly reported events were respiratory tract infections, ocular infections, and injection site reactions (2 vs 3, 0 vs 2, and 0 vs 2 events, respectively), and no serious adverse events occurred.
l’Ami and colleagues note that the median duration of adalimumab treatment was 5.5 years for participants in the prolongation group, but emphasize that “[a]s the concentration–response relationship is based on 28 weeks of treatment we do expect interval prolongation to be possible shortly after initiation of adalimumab treatment.”
And the researchers conclude that “patients with RA on adalimumab with serum trough concentrations above 8 μg/mL can safely prolong their dosing interval to every 3 weeks without loss of disease control.”
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