title: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov; http://www.clinicaltrials.gov; NCT00076726.
authors.affiliation: Centocor Research and Development, Malvern, PA, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Visvanathan
authors.forename: Mahboob U
authors.initials: MU
authors.lastname: Rahman
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: Stephen
authors.initials: S
authors.lastname: Xu
authors.forename: Ana
authors.initials: A
authors.lastname: García-Martínez
authors.forename: Marta
authors.initials: M
authors.lastname: Segarra
authors.forename: Ester
authors.initials: E
authors.lastname: Lozano
authors.forename: Georgina
authors.initials: G
authors.lastname: Espígol-Frigolé
authors.forename: José
authors.initials: J
authors.lastname: Hernández-Rodríguez
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cid
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D004359:Drug Therapy, Combination; D015870:Gene Expression; D013700:Giant Cell Arteritis / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D012074:Remission Induction
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005938:Glucocorticoids; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D007371:Interferon-gamma; D000069285:Infliximab