Background For about 15 years biological compounds belong to the therapeutic options for the treatment of rheumatoid arthritis. By targeting of tumor necrosis factor alpha (TNFα), one of the key cytokines in the pathogenesis of rheumatoid arthritis (RA), patients benefit in terms of disease activity as well as radiologic progression. The application of biologic substances is subject to a risk to develop antibodies against these structures causing adverse events or loss of efficacy.
Objectives It was the aim of the study to analyse the occurrence of anti-drug antibodies in the course of a long term treatment of patients with rheumatoid arthritis with etanercept (ETN).
Methods In this retrospective analysis sera from 100 RA patients obtained during an up to 4 years treatment period with etanercept (after 6, 12, 24, 36 and 48 months) and 43 adalimumab (ADL)-treated patients were included for determination of anti-drug antibodies. If available the first serum sample obtained at least 2 weeks after discontinuation of ETN treatment (due to side effects, non-response, remission or surgery) was included for analysis to exclude any interference with high drug levels. For the determination of anti-ETN and anti-ADL levels Promonitor® -anti-ETN and –anti-ADL assays (Proteomika, Spain) were used according to the manufacturer's instructions. Both assays are designed as bridging assays with cut-off values of 142 AU/ml and 3.5 AU/ml for ETN and ADL, respectively. For calculation of results a data analysis software (http://www.myassays.com) was used.
Results No anti-ETN antibodies were found in 100 RA patients, neither in the course of treatment nor in samples from 72 of these patients obtained after discontinuation of ETN treatment after mean 36.3 months (range 5-78 months). However, in the ADL-treated cohort anti-ADL antibodies were found in 51.2% of patients (22 out of 43) after discontinuation of therapy after mean 23.4 months (range 3-77 months).
Conclusions Our study confirms the lack of anti-drug antibodies in a large cohort of RA patients in the course of a long-term treatment with ETN over up to 4 years. The absence of anti-ETN antibodies in serum samples after discontinuation of therapy confirms this result by exclusion of false negative results resulting from interference with high etanercept levels in the course of treatment.
Acknowledgements Supported by Pfizer Pharma GbmH
Disclosure of Interest S. Drynda Grant/research support from: Pfizer Pharma GmbH, R. Beuermann: None declared, J. Kekow: None declared