# The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors

## TL;DR

This study found that rheumatoid arthritis flares are more likely when drug levels of TNF inhibitors fall below 1 mg/L, and tapering methotrexate first increases antibodies against adalimumab.

## Contribution

The study identifies a serum concentration threshold for TNF inhibitors linked to RA flares and examines the effect of methotrexate tapering on immunogenicity.

## Key findings

- Most RA flares occurred when serum concentrations of adalimumab and etanercept dropped below 1 mg/L.
- Adalimumab remained detectable in the blood longer than etanercept after cessation.
- Tapering methotrexate first increased anti-drug antibodies against adalimumab, but did not affect its serum concentration.

## Abstract

Objectives: To assess the association between serum concentrations of adalimumab (ADL) and etanercept (ETN) and the occurrence of a flare in rheumatoid arthritis (RA) patients who are tapering methotrexate (MTX) or their TNF inhibitor. In addition, we explored the impact of tapering MTX on immunogenicity in patients with longstanding ADL use. Methods: ADL and ETN serum concentrations and anti-drug antibodies (ADAs) quantified with a drug-tolerant assay were determined in all RA patients who participated in the TARA trial. Within the TARA trial, two tapering strategies were compared, namely gradually tapering MTX followed by tapering a TNF-inhibitor (ADL or ETN) or vice versa. Results: In the current analysis, 111 RA patients who strictly followed the tapering strategy and had >3 blood samples were included, of them 41% tapered ADL and 59% tapered ETN. Both ADL and ETN concentrations decreased during tapering and stopping, but ADL was longer detectable after cessation compared to ETN. If MTX was tapered first, more ADAs against ADL were detectable in the serum, but it did not affect the serum concentrations. Conclusions: Our data showed that the majority of flares occur when the median serum concentration of ADL and ETN falls below 1 mg/L. If MTX is tapered first, there is a notable increase in the detection of ADAs, but this does not impact the median ADL serum concentration.