OP0297 Calprotectin (S100A8/9) as Serum Biomarker for Clinical Response in Proof-Of-Concept Trials in Axial and Peripheral Spondyloarthritis

Abstract

Background Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick “go/no go” decisions in the clinical development of new treatments. Objectives We aimed to identify and validate serum biomarkers to predict clinical response in spondyloarthritis (SpA) PoC trials. Methods The candidate biomarkers high sensitive-C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and Vascular Endothelial Growth Factor (VEGF) were determined by ELISA in healthy controls (n=20) and SpA patients before and after 2 weeks of infliximab (n=18) or placebo (n=19) treatment. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab and peripheral SpA with etanercept. Results Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P<0.001) and MMP-3 (P=0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (P<0.001) and hs-CRP (P<0.001) levels, with a similar trend for MMP-3 (P=0.063). The Standardized Response Mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (1.26), good for hs-CRP (0.96) and moderate for MMP-3 (0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers of treatment response in axial SpA as evaluated in 2 separate cohorts. All 3 markers reflected response to etanercept treatment in peripheral SpA with SRMs above 0.5. Conclusions Calprotectin and hs-CRP are good serum biomarkers to predict clinical response at the group level in small-scale, short term PoC trials in SpA. Disclosure of Interest M. Turina: None declared, N. Yeremenko: None declared, J. Paramarta: None declared, L. De Rycke: None declared, D. Baeten Grant/research support: AbbVie, Centocor, Janssen-Cilag, MSD, Novartis, and Pfizer, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Centocor, Janssen, MSD, Novartis, Pfizer, and UCB DOI 10.1136/annrheumdis-2014-eular.2837

Infliximab infusion and its relation on disease activity, severity and acute phase reactant protein in Iraqi patients with ankylosing spondylitis

“…Studies have shown that TNF inhibitors improve healthrelated quality of life, patient-reported outcomes, anemia, Creactive protein (CRP) levels, and sleep quality in patients with AS because TNF inhibitors control inflammation in the spine, as measured by various MRI sequences [14] . In the current study we found that mean serum level of hs-CRP higher in patients treated with conventional treatment, than in patients on biological treatment (infliximab infusion) and this difference is statistically significant (P-value = 0.0235) and these results were in accordance with other study done by Turina et al who found that hs-CRP is a useful biomarker of inflammation in this context as, despite not being elevated in all patients at baseline, it rapidly and significantly decrease in both axial and peripheral SpA treated with either infliximab or etanercept [15] . In the current study we found that mean level of ESR higher in patients treated with conventional treatment, than in patients on biological treatment (infliximab infusion) and this difference is not statistically significant (P-value = 0.3051) which disagrees with Luc et al that is found that there was a strong association between ESR level at baseline and clinical response to treatment with anti-TNF after 3 months, supporting a potential distinctive exploitation of ESR in identifying AS patients suitable for treatment with anti-TNF, which is also of particular relevance in light of the costs of biologics and the side effects of these drugs and this disagreement due to difference in sample size and difference in study population [16] .…”