Lene Surland Knudsen¹, Merete Lund Hetland², Julia Sidenius Johansen¹, Henrik Skjødt², Niels Daugaard Peters³, Ada Colic⁴, Karin Grau⁵, Hans Jørgen Nielsen⁶ and Mikkel Østergaard^1,2

¹Department of Rheumatology, Copenhagen University Hospital at Herlev, Denmark. ²Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Denmark. ³Department of Rheumatology, Hjørring County Hospital, Denmark. ⁴Department of Rheumatology, Esbjerg County Hospital, Denmark. ⁵Department of Rheumatology, Kolding County Hospital, Denmark. ⁶Department of Surgical Gastroen- terology, Copenhagen University Hospital at Hvidovre, Denmark.

Abstract

Changes in plasma IL-6, plasma VEGF and serum YKL-40 were determined in rheumatoid arthritis (RA) patients during treatment with etanercept alone or in combination with methotrexate. Twenty-five patients with active RA (DAS28  3.2) were randomized to receive etanercept (25 mg sc. biweekly) plus methotrexate (n = 12) or etanercept alone (n = 13). Plasma IL-6, plasma VEGF and serum YKL-40 were determined by ELISA. The 3 biomarkers and DAS28 scores were evaluated at baseline and after 4, 8, 12 and 16 weeks of treatment. At inclusion all patients had significantly (p  0.001) elevated plasma IL-6, plasma VEGF and serum YKL-40 compared to healthy subjects. Eighteen patients responded to treatment (pooled data from both treatment groups), and they had significant (p  0.05 to p  0.001) decreases in plasma IL-6, plasma VEGF, serum YKL-40, ESR and DAS28 after 4 weeks of treatment and throughout the study (except serum YKL-40 at week 16). Plasma IL-6 showed the largest reductions. Non-responders had unchanged biomarkers. At week 16 the patients with DAS28  3.2 had lower levels compared to baseline values in plasma IL-6 (p = 0.005), plasma VEGF (p = 0.014), and ESR (p = 0.024).

Plasma IL-6, plasma VEGF and serum YKL-40, which reflect different aspects of the inflammatory process, may provide useful information regarding early differentiation of responders from non-responders.