Longitudinal TNF Levels Mainly Stable With Adalimumab in RA
Early low TNF strongly associated with formation of antidrug antibodies, may predict nonresponse
FRIDAY, Feb. 1, 2019 (Pharmacist's Briefing) -- For patients with rheumatoid arthritis (RA), longitudinal tumor necrosis factor (TNF) concentrations are mainly stable during adalimumab treatment, although early low TNF is strongly linked to nonresponse to treatment, according to a study published in the Jan. 30 issue of Science Translational Medicine.
Lea C. Berkhout, from Sanquin Research in Amsterdam, and colleagues explored the dynamics of circulating TNF during adalimumab treatment using a competition enzyme-linked immunosorbent assay that can quantify TNF in the presence of large amounts of TNF inhibitor.
The researchers found that circulating TNF increased an average of >50-fold upon treatment and reached a stable concentration in time for most of the 193 consecutive adalimumab-treated patients with RA. In 30 healthy volunteers, a similar increase in TNF was seen after one dose of adalimumab. TNF was in complex with adalimumab during treatment and could be recovered as inactive 3:1 adalimumab-TNF complexes. There was no quantitative correlation between TNF and adalimumab concentration. There was a correlation for low TNF concentration at week 4 with a higher frequency of antidrug antibodies (ADAs) at subsequent time points, less frequent methotrexate use at baseline, and less frequent remission after 52 weeks. Early low TNF concentrations correlated with ADAs in healthy volunteers.
"These findings indicate that TNF concentrations in circulation do not reflect (suppressed) inflammation and that the majority of TNF likely does not originate from pathological processes," the authors write.
Several authors disclosed financial ties to the pharmaceutical industry.