Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etanercept treatment in seronegative rheumatoid arthritis

Abstract

Objective: To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival.

Method: We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital (1999–2008), of whom 16 had seronegative and 129 seropositive RA. TNF-α in serum was quantified using enzyme-linked immunosorbent assay in samples from the onset of treatment and at 6 week follow-up. Drug survival time was used to evaluate the long-term efficacy of etanercept.

Results: Levels of TNF-α were significantly increased at follow-up compared to at the start. At the 6 week follow-up, circulating TNF-α mainly comprised TNF-α in complex with etanercept. Longer drug survival time correlated with increased TNF-α at 6 week follow-up in the patients with seronegative RA, but not in the seropositive patients.

Conclusion: We demonstrated that levels of circulating TNF-α increased in almost all individuals after initiation of treatment with etanercept and that this increase mainly comprised TNF-α in complex with etanercept. More importantly, this increase may predict drug survival in adults with seronegative, but not seropositive, RA and suggests that measuring TNF-α/etanercept complexes in serum may be relevant in patients with seronegative RA.

Acknowledgements

We wish to thank Maria Jacobsson for excellent help with collecting and categorizing the serum samples.

The work was supported by grants from the Swedish Rheumatism Association, the Medical Faculty of the University of Lund, Alfred Österlund’s Foundation, the Anna-Greta Crafoord Foundation, Greta and Johan Kock’s Foundation, the Samariten Foundation, Fanny Ekdahl Foundation, the Jerring Foundation, the Crafoord Foundation, and the Thelma Zoegas Foundation.

Supporting Information

Additional Supporting Information may be found in the online version of this article

Supplementary Figure S1. Tumour necrosis factor/etanercept complexes in the circulation.

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Additional information

Funding

This work was supported by the Alfred Österlund’s Foundation, The Swedish Rheumatism Association, The Samariten Foundation, Greta and Johan Kock’s Foundation, The Jerring foundation, The Crafoord foundation, The Thelma Zoegas Foundation, Fanny Ekdahl foundation, The Anna-Greta Crafoord Foundation: [Grant Number xxxx, xxx].