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THU0204 The (un)coupling of inflammation and destruction in patients treated with rhil-1ra
  1. AM Van Gestel1,
  2. PL Van Riel1,
  3. C Lindsay2,
  4. JM Robinson2
  1. 1Department of Rheumatology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
  2. 2Amgen, Thousand Oaks, USA

Abstract

Background Previous studies have shown that recombinant human interleukin-1 receptor antagonist (rhIL-1ra) has an effect on RA disease activity and on the progression of radiographic damage. In animal models an uncoupling between joint inflammation and joint destruction is found with rhIL-1ra. We hypothesised that in case of uncoupling the association found between these disease aspects would be different for patients treated with rhIL-1ra versus placebo.

Objectives To study the coupling between disease activity and radiographic damage in a 24-week placebo controlled trial of rhIL-1ra in 472 RA patients.

Methods Since no clear dose-response relation has been shown for the 3 active groups (30, 75, 150 mg/d), these groups were combined for the analyses.

Models were made to explain the Larsen progression score (LPS) by treatment group (TG), EULAR response (EUL), and TG*EUL interaction term. In a different model the EUL was replaced with the endpoint DAS28.

Results At 24 weeks LPS was partly explained by TG (p = 0.02) but not by EUL. Exchanging EUL for DAS28, LPS was partly explained by DAS28 (p < 0.001) and TG*DAS28 (p = 0.02). The higher the DAS28 the higher the LPS, and this was more pronounced in the placebo group.

Conclusion At 24 weeks the association between x-ray progression and inflammation is more pronounced in the placebo group, suggesting an uncoupling with active rhIL-1ra treatment. Further data analyses, including the 24 week extension of the trial, might confirm these findings.

Abstract THU0204 Table 1

Reference

  1. Breshnihan B, Alvaro-Gracia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998;41:2196–204

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