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

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.