Inflammatory and angiogenic serum profile of refractory rheumatoid arthritis

The objective was to pinpoint specific circulating angiogenic and inflammatory markers of refractory and active RA. We used Luminex technology to measure the concentrations of 17 RA-representative serum angiogenic and inflammatory markers in 211 RA patients categorized into three groups: refractory (failure of 2 or more targeted therapies) active (persistence of objective signs of disease activity) RA, non-refractory (failure of ≥ 1 csDMARDs or a first line of targeted therapy) active RA and non-active RA (DAS28 ≤ 3.2). Refractory and non-refractory active RA patients differed in disease duration, structural damage and the utilization of biologic therapy. The concentrations of the 17 markers failed to distinguish refractory from non-refractory RA patients. The comparison of active and non-active RA only revealed a strong increase of IL-6 concentration in active RA. Refractory active RA exhibited a limited correlation profile showing only three correlations with markers of disease activity, not significantly different from whose of non-active RA. By contrast, in non-refractory active RA patients, correlograms revealed an extensive proinflammatory and proangiogenic correlation profile with 12 markers correlating with inflammation markers or disease activity. In conclusion, no classical marker of RA emerged as specific for refractory disease in this study. Moreover, refractory and active RA patients exhibited only few correlations with disease activity markers, despite the persistence of clinical and biological signs of disease activity. This may suggest that additional molecules may be implicated in refractory disease outside those herein selected. These findings also highlight the potential limitations of serum analysis in refractory active RA.