Assessing Drug Bioavailability or Anti-Drug Antibody to Guide Use of TNF Inhibitors

Monitoring drug and anti-drug antibodies (ADAb) may assist in adjusting the dosage of tumor necrosis factor alpha (TNF) inhibitors or switching to a different drug in patients with chronic inflammatory arthritis, according to study results published in Autoimmunity Reviews.

Previous studies have reported that the rate of TNF inhibitors treatment failure for patients with rheumatic musculoskeletal diseases is up to 40%. While the causes for treatment failure are not clearly understood, drug immunogenicity and production of ADAb may play an important role.

Drug/ADAb levels can be determined using enzyme-linked immunosorbent assays (ELISAs) or with radioimmunoassay (RIA) antigen binding tests. Reporter-gene assay (RGA) is another assay, which is a cell-based technique able to discriminate between neutralizing and inactive ADAb.

The multicenter, cross-sectional study was completed to compare and validate ELISA and RGA assays detecting TNF inhibitors and corresponding ADAb levels. Following validation, the ELISA was used in a multicenter prospective study that included biologic-naïve participants starting treatment with adalimumab or etanercept.

The cross-sectional study included 163 patients with rheumatoid arthritis (RA) treated with TNF inhibitors, including 67 infliximab-treated patients, 49 adalimumab-treated patients, and 47 etanercept-treated patients. All patients completed testing for drug and ADAb levels using commercially available ELISA and RGA at baseline and after 3 and 6 months of treatment.

Using the ELISA assay, ADAbs were detected in 14.1% of the participants and drug levels were detected in 83.4%. In comparison, using RGA assay, ADAb were detected in 12.9% and drug levels were detected in 71.8% patients. Only 1 of 117 samples was positive for both drug and ADAb. The assays performed comparably and the agreement was moderate/substantial.

As both assays performed comparably in patients treated with adalimumab and etanercept in the cross-sectional study, the researchers used the ELISA in the prospective study that included 70 participants, of which 59 had RA and 11 had juvenile idiopathic arthritis.

At 3 months, 2 adalimumab-treated patients with RA developed ADAb and the response to treatment was lost. In addition, 2 other patients with RA developed ADAb after 6 months, one with a moderate response and another with no response to treatment.  Primary failure was found in 2 additional patients with no ADAb.

All etanercept-treated patients had undetectable ADAb levels and all had a moderate to good response to therapy. Secondary failure was documented in one patient at 6 months.

“[O]ur findings support drug and ADAb monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis,” concluded the researchers.

Reference

Bodio C, Grossi C, Pregnolato F, et al. Personalized medicine in rheumatoid arthritis: How immunogenicity impacts use of TNF inhibitors. Autoimmun Rev. 2020;19(5):102509.