Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort

Gottenberg, Jacques-Éric; Dayer, Jean‐Michel; Lukas, Cédric; Ducot, B.; Chiocchia, Gilles; Cantagrel, A.; Saraux, Alain; Roux‐Lombard, Pascale; Mariette, Xavier

doi:10.1136/annrheumdis-2011-200975

Cited by 75 publications

(58 citation statements)

References 26 publications

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“…A recent study showed that baseline IL-6 was significantly higher in early RA than in undifferentiated early arthritis (8). Despite the fact that CRP synthesis is notoriously IL-6 dependent, this study showed that patients with detectable IL-6 at enrollment displayed higher risk for radiographic progression independently of systemic inflammation assessed by CRP level.…”

Section: Supported By the Espoir (Etude Et Suivi Des Polyarthritesmentioning

confidence: 49%

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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

Baillet¹,

Gossec

Paternotte

et al. 2015

Arthritis Care & Research

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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 Indiff erenci ees R ecentes) 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 timeintegrated 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. Conclusion. IL-6 level was a marker of US synovitis at baseline. Repeated measurements of IL-6 are associated with structural damage.

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Section: Supported By the Espoir (Etude Et Suivi Des Polyarthritesmentioning

confidence: 49%

“…Moreover, IL-6 concentration was detected using sensitive techniques (8). Furthermore, we could study the 3-year radiologic progression, whereas most of the other studies focused on the short-term, usually 12 months, radiologic progression.…”

Section: Discussionmentioning

confidence: 99%

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

Baillet¹,

Gossec

Paternotte

et al. 2015

Arthritis Care & Research

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“…However, we noted an increase in IL-6 expression by monocytes over time in the EIA cohort, which may explain the observed increase in serum IL-6 between EIA and established RA patients. Recently published data from other European early arthritis cohorts [42,43] have detected increased IL-6, particularly in patients with very early RA compared to undifferentiated arthritis [43]. As the majority of patients in our cohort had RA, we had insufficient power to detect a difference between these two groups.…”

Section: Cd4mentioning

confidence: 81%

Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

Gullick

Abozaid

Jayaraj

et al. 2013

Clinical and Experimental Immunology

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“…The diagnostic tests were MRI of hands and feet (4 separate MRIs), interleukin-6 (IL-6) serum level test (13), B cell-related gene expression in whole blood (14), a genetic assay with susceptibility of single nucleotide polymorphisms for RA (15), and an almost perfect diagnostic test with a sensitivity of 0.99 and specificity of 0.99. The tests were evaluated employing assumed test characteristics and costs supplied by the Dutch Healthcare Authority (16) and, where those were not available, by using expert opinion.…”

Section: Methodsmentioning

confidence: 99%

“…IL-6 is a cytokine that is present in inflammation. A recent evaluation of IL-6 serum test performance in an early arthritis ESPOIR study cohort showed a sensitivity of 0.70 and a specificity of 0.53 for the detection of RA among the inflammatory arthritis patients (13). We used these test properties and assumed e50 per test, based on expert opinion.…”

Section: Methodsmentioning

confidence: 99%

Cost‐Effectiveness Model for Evaluating New Diagnostic Tests in the Evaluation of Patients With Inflammatory Arthritis at Risk of Having Rheumatoid Arthritis

Luime

Buisman

Oppe

et al. 2016

Arthritis Care & Research

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Objective. New opportunities have emerged for early diagnosis with the arrival of new technologies that assess the impact of genomics, proteomics, metabolomics, and cytomics on rheumatoid arthritis (RA) risk. This early health technology assessment study assesses the short-term cost effectiveness of 4 add-on diagnostic tests in early inflammatory arthritis patients at risk of RA. Methods. We modeled 4 diagnostic add-on tests to the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria, covering the first year after diagnosis, using Rotterdam Early Arthritis Cohort data. Sensitivity, specificity, and costs were assigned to the magnetic resonance imaging of hands and feet (sensitivity 0.90, specificity 0.60, cost e756), interleukin-6 (IL-6) serum level test (sensitivity 0.70, specificity 0.53, cost e50), B cell-related gene expression (sensitivity 0.60, specificity 0.90, cost e150), and gene assay for RA (sensitivity 0.40, specificity 0.85, cost e750), based on literature and expert opinion. Outcomes were evaluated using the unweighted diagnostic net benefit (UDNB) and the incremental costeffectiveness ratio (ICER) in all patients (n 5 552), intermediate-risk patients (n 5 263), and seronegative patients (n 5 329). Results. The highest UDNB was found when using the B cell assay in intermediate-risk patients (43%, ICER e5,314), while the IL-6 test in seronegative patients resulted in the lowest UDNB (211.4%, ICER e7,650). If a threshold of e20,000 is applied, the B cell assay would be preferred over the other alternatives, with a 78% probability of being cost effective for intermediate-risk patients, 57% for all patients, and 73% for seronegative patients. Conclusion. Diagnostic add-on tests favoring specificity over sensitivity with a headroom less than e370 per test are cost effective, with the largest diagnostic benefit occurring in intermediate-risk patients.

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Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort

Abstract: Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.

Cited by 75 publications

References 26 publications

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

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

Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

Cost‐Effectiveness Model for Evaluating New Diagnostic Tests in the Evaluation of Patients With Inflammatory Arthritis at Risk of Having Rheumatoid Arthritis

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