Tissue and serum markers of inflammation during the follow-up of patients with giant-cell arteritis--a prospective longitudinal study

Abstract

Objective. To evaluate the association between inflammatory markers and relapse in GCA patients longitudinally assessed in a clinical trial of infliximab and glucocorticosteroids.Methods. Forty-four newly diagnosed GCA patients in glucocorticosteroid-induced remission were randomized to receive infliximab 5 mg/kg or placebo plus daily glucocorticosteroids, tapered using a standardized schedule. Sera were analysed for inflammatory markers at multiple, pre-defined time points. Temporal artery biopsies were performed in four patients before and after treatment to analyse changes in inflammatory and vascular remodelling marker expression.Results. Thirteen of 44 patients relapsed. Similar proportions of relapsed patients were present in both treatment arms. ESR, CRP, intercellular adhesion molecule (ICAM)-1, TNF-α, and IL-12p40 were significantly elevated near relapse. In post-treatment biopsies, mRNA expression of pro-inflammatory cytokines decreased, while vascular remodelling factors increased relative to baseline biopsies. Tissue IL-12p40 and IFN-γ mRNA remained elevated in relapsing vs remitting patients.Conclusion. Despite prior findings of high concentrations of TNF-α in temporal artery biopsies of GCA patients, infliximab plus glucocorticosteroids did not result in improved clinical outcomes. Increased measures of this biomarker did not provide useful insight into the relative importance of TNF-α in the pathogenesis of GCA. Gene expression analysis in paired temporal artery biopsies pre- and post-treatment revealed decreased inflammatory activity and active vascular remodelling following treatment. In relapsing patients, increased expression of IFN-γ and IL-12p40 in post-treatment biopsies suggests a role in sustaining disease and setting the stage for relapse during treatment withdrawal.Trial registration. ClinicalTrials.gov; http://www.clinicaltrials.gov; NCT00076726.

Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients

“…The number of patients diagnosed with GCA by 2050 is projected to be over 3 million in Europe, North America, and Oceania, representing a significant clinical and financial challenge [8]. Several previous reports have described potential serological markers for GCA [9][10][11][12][13][14][15][16][17][18], among them cytokines, chemokines, growth factors, cell adhesion molecules, and matrix metalloproteinases (MMPs). In 2000, Weyand et al emphasized that interleukin (IL)-6 may act as a biological marker of GCA activity in untreated and treated GCA patients [19].…”

Outcome of a glucocorticoid discontinuation regimen in patients with inactive systemic sclerosis

“…However, identification of the right patient and of the most appropriate tapering scheme is hampered by the extreme paucity of studies on this topic. Glucocorticoid discontinuation has been studied in diseases such as SLE [30][31][32][33], vasculitis [34][35][36][37], rheumatoid arthritis [38][39][40], but never in SSc patients.…”

Giant Cell Arteritis: Beyond Corticosteroids

“…In contrast, a Matrigel culture model found that culture with dexamethasone significantly reduced IFN-c mRNA transcription [32], and in a study that included four paired pre-and post-treatment biopsies, IFN-c mRNA was found to reduce with treatment, but with higher levels still being found in patients prone to relapse [33].…”