Evaluation of serum interleukin-6 level as a surrogate marker of synovial inflammation and as a factor of structural progression in early rheumatoid arthritis: results from a French national multicenter cohort.
OBJECTIVE
Interleukin-6 (IL-6) is a key cytokine in rheumatoid arthritis pathogenesis. We aimed to analyze the association between IL-6 serum levels and joint inflammation at baseline and the correlation of time-integrated IL-6 values with structural damage during the first 36 months of early arthritis.


METHODS
IL-6 was assessed by 2 different methods in 813 patients of the French early arthritis cohort ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) over 36 months. IL-6 and C-reactive protein (CRP) changes were correlated to radiographic progression assessed by the total Sharp/van der Heijde score (SHS). Synovium inflammation was assessed in a subgroup of 126 patients by ultrasonography (US). The relationship between SHS change and IL-6 or CRP levels at baseline was investigated by a univariate regression and a multivariable analysis. A longitudinal model nested by visit and patient was conducted to assess the role of IL-6 on SHS at each visit.


RESULTS
At baseline, IL-6 was more strongly correlated with the swollen joint count than CRP level. In the univariate analysis, the time-integrated value of IL-6 was more strongly correlated with the swollen joint count and the variation of SHS than time-integrated CRP level. Baseline IL-6 was not independently associated with SHS change. Longitudinal models nested by patient showed that IL-6 levels were associated with structural damage independently from the Disease Activity Score in 28 joints, smoking status, rheumatoid factor, and anti-citrullinated protein peptide antibody serology, treatments, and CRP levels.


CONCLUSIONS
IL-6 level was a marker of US synovitis at baseline. Repeated measurements of IL-6 are associated with structural damage.
GREPI UJF CNRS, Grenoble, France.
Athan
A
Baillet
UPMC Université Paris 06, GRC-UPMC 08 (EEMOIS), Assistance Publique Hôpitaux de Paris, Pitié Salpêtrière Hospital, Paris, France.
Laure
L
Gossec
Paris-Descartes University, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Paris, France.
Simon
S
Paternotte
Paris-Descartes University, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Paris, France.
Adrien
A
Etcheto
Lapeyronie University Hospital, Montpellier I University, Montpellier, France.
Bernard
B
Combe
Université Paris 7 Denis Diderot, UFR de Médecine, and Assistance Publique Hôpitaux de Paris, Hôpital Bichat, Paris, France.
Olivier
O
Meyer
Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Université Paris-Sud, Institut Pour la Santé et la Recherche Médicale Paris, France.
Xavier
X
Mariette
Strasbourg University Hospital, Strasbourg, France.
Jacques-Eric
JE
Gottenberg
Paris-Descartes University, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Paris, France.
Maxime
M
Dougados
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013585:Synovitis / Q000097:blood* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D014463:Ultrasonography
D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6