In patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with sustained minimal disease activity (MDA), tapering of the tumor necrosis factor (TNF) inhibitor etanercept can be performed without a loss of efficacy, according to results of a study published in Scandinavian Journal of Rheumatology.
The researchers sought to compare dose-interval prolongation among patients who continued treatment with etanercept compared with those who received standard etanercept dose. The success rate associated with etanercept discontinuation was also assessed.
An 18-month, open-label, randomized controlled trial was conducted at the Amsterdam Rheumatology and Immunology Center, located in Reade, The Netherlands.
Patients with RA, PsA, or AS were included in the study if they had received treatment with the standard dose of etanercept — 50 mg administered subcutaneously once weekly or 25 mg administered subcutaneously twice weekly for at least 6 months prior to the study enrollment. Patients were also required to fulfil the MDA criteria for at least the previous 6 months to be eligible in the study.
The 6-month randomized trial included the first phase of the study, in which etanercept dose was decreased by 50% by doubling the dosing interval at baseline and discontinuing etanercept 6 months later (intervention group) or etanercept was continued in the standard dose for 6 months and the dosing interval was doubled thereafter (control group).
On experiencing a disease flare (defined as “loss of disease control”), the standard dose of etanercept was reinstituted in the intervention group.
In the second phase of the study, participants in the intervention group could discontinue treatment with etanercept if they continued to receive the reduced dose and met the criteria for MDA.
The primary study outcome was the percentage of patients who maintained MDA at the 6-month follow-up.
A total of 160 participants (79 with RA, 41 with PsA, and 40 with AS) with sustained MDA were enrolled in the current study; 159 individuals were included in the intent-to-treat analysis. Researchers noted that MDA was maintained in 68% (n=103/151) of participants during the first 6 months of follow-up.
Overall, 63% of individuals in the intervention group and 74% of those in the control group maintained MDA (relative risk ratio, 0.83; 95% CI, 0.70-1.03; P =.15).
After dividing the intervention group into subgroups, the researchers found that 60% of participants with RA, 57% of those with PsA, and 55% of those with AS continued to be in MDA following 6 months of interval prolongation. In the control group, 76%, 70%, and 65% of participants with RA, PsA, and AS, respectively, continued to be in MDA after 6 months.
Median etanercept levels decreased from 1.50 µg/mL (IQR, 1.06-2.65 µg/mL) to 0.46 µg/mL (IQR, 0.28-0.92 µg/mL). Overall, 40% of participants discontinued etanercept successfully and maintained MDA for at least 6 months.
One of the limitations of the study was its design. A noninferiority trial design with a larger number of patients may have yielded more definite conclusions.
The researchers concluded that the findings from the current study demonstrated that low concentrations of etanercept were sufficient to control disease activity. However, the risk for minor or major disease flares may be considerable, even among individuals who continued to receive the standard dose of etanercept.
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Ruwaard J, L’Ami MJ, Kneepkens EL, et al. Interval prolongation of etanercept in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a randomized controlled trial. Scand J Rheumatol. Published online March 2, 2022. doi:10.1080/03009742.2022.2028364