Introduction: Rheumatoid arthritis (RA) causes inflammation of the joints which if left untreated or inadequately treated may result in joint- and bone destruction and facilitate development of systemic co-morbidities such as cardiovascular diseases and inflammatory lung diseases. The introduction of bDMARDs have revolutionized the treatment options for RA. One of these bDMARDs is etanercept, a fusion protein made by genetic recombination. Etanercept works as a decoy receptor for TNF-a resulting in decreased cellular signaling from TNF-a binding to its target receptor. However, about 30% to 40% of RA patients do not achieve remission or low disease activity in response to treatment with anti-TNF-a treatment.

Aim: The aim of this study was to investigate the effects of long-term treatment of RA with etanercept and to identify biomarkers to monitor treatment response in these patients.

Methods: Serum samples collected from 12 etanercept-treated RA patients before treatment, and after three, six, and 12 months of treatment, respectively were analyzed proteomically by LC-MS/MS and analyzed by quantification of cfDNA levels.

Results: 79 proteins were found to have a significantly altered abundance as a result of etanercept treatment either for three, six or 12 months. Out of these, five potential etanercept responsive bi- omarkers were identified. Furthermore, a continuous, significant fall in cfDNA concentration was observed in the serum samples.

Conclusion:Five candidate biomarkers of etanercept treatment response in RA patients were identified. Especially vitamin D-binding protein, pregnancy zone protein, and plasma kallikrein were found to be interest- ing potential biomarkers. Furthermore, lowered cfDNA concentrations may have the ability to be used as a biomarker of RA remission. Future studies are needed to expand the knowledge of the potential biomarkers and their relation to inflammation in RA.