Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data

International audienceIntroduction Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX).Methods We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for ≥3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS≥5 points during the first year.Results At 1 year, the mean vSHS score was 1.7±5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC) <0.7. The AUC for the BEST and SONORA matrices were 0.73 and 0.76. Presence of rheumatoid factor (RF)—or anti-citrullinated protein antibodies (ACPAs) and initial structural damage were always predictive of RRP at 1 year. Disease Activity Score in 28 joints (DAS28) and C reactive protein (ASPIRE threshold) were not associated with RRP.Conclusions Matrices to identify patients at risk of RRP tested in the ESPOIR cohort seem to perform moderately. There is no matrix that shows clearly superior performance

Method of treating rheumatoid arthritis

The invention relates to a method of treating rheumatoid arthritis in a patient comprising the steps of:a) providing a biological sample from a patient,b) measuring the level of soluble VE-cadherin in the biological sample obtained at step a);c) comparing said level of soluble VE-cadherin with a predetermined reference value, andif the level of soluble VE-cadherin measured at step b) is higher that the predetermined reference value,treating the patient until a basal level of soluble VE-cadherin is reached

Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients from the community treated with methotrexate or leflunomide: results from the ESPOIR cohort

International audienceIntroductionEarly rheumatoid arthritis (RA) patients may show rapid radiographic progression (RRP) despite rapid initiation of synthetic disease-modifying anti-rheumatic drugs (DMARDs). The present study aimed to develop a matrix to predict risk of RRP despite early DMARD initiation in real life settings.MethodsThe ESPOIR cohort included 813 patients from the community with early arthritis for ResultsWe analyzed data for 370 patients. The mean Disease Activity Score in 28 joints was 5.4 ± 1.2, 18.1% of patients had typical RA erosion on radiographs and 86.4% satisfied the 2010 criteria of the American College of Rheumatology/European League Against Rheumatism. During the first year, mean change in vSHS was 1.6 ± 5.5, and 41 patients (11.1%) showed RRP. A multivariate logistic regression model enabled the development of a matrix predicting RRP in terms of baseline swollen joint count, C-reactive protein level, anti-citrullinated peptide antibodies status, and erosions seen on radiography for patients with early RA who received DMARDs.ConclusionsThe ESPOIR matrix may be a useful clinical practice tool to identify patients with early RA at high risk of RRP despite early DMARD initiation

Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis

BACKGROUND: The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24). METHODS: Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis. RESULTS: The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34x10(-6), OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%. CONCLUSION: Our results support the contribution of the IRF5, SPP1 and TNFSF13B genotypic combination in the response to RTX for RA at W24

Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis

BACKGROUND: The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24). METHODS: Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis. RESULTS: The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34x10(-6), OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%. CONCLUSION: Our results support the contribution of the IRF5, SPP1 and TNFSF13B genotypic combination in the response to RTX for RA at W24

Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis

BACKGROUND: The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24). METHODS: Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis. RESULTS: The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34x10(-6), OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%. CONCLUSION: Our results support the contribution of the IRF5, SPP1 and TNFSF13B genotypic combination in the response to RTX for RA at W24

Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its gamma Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies

International audienceTo identify the targets recognized by anti-carbamylated protein antibodies (anti-CarP) in patients with early Rheumatoid Arthritis (RA), to study the cross-reactivity between anti-CarP and anti-citrullinated protein antibodies (ACPA) and to evaluate their prognostic value. 331 patients (184 RA and 147 other rheumatisms) from the Very Early Arthritis (VErA) French cohort were analyzed. We performed mass spectrometry analysis of RA sera displaying anti-CarP activity and epitope mapping of the carbamylated fibrinogen gamma chain to identify immunodominant peptides. The specificity of these targets was studied using competition assays with the major antigens recognized by ACPA. The prognostic value of anti-carbamylated fibrinogen IgG antibodies (ACa-Fib IgG) was compared to that of anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-CarP using an in-house ELISA. Besides the alpha chain, the gamma chain of fibrinogen, particularly one immunodominant epitope that has a specific reactivity, was identified as a circulating carbamylated target in sera. The prevalence of ACa-Fib was 37% at baseline and 10.9% for anti-CCP-negative RA. In anti-CCP-negative patients, ACa-Fib positivity was associated with a more inflammatory and erosive disease at baseline but not with rapid radiological progression, which remains strongly related to anti-CCP antibodies. Fibrinogen seems to be one of the antigens recognized in vivo by the anti-CarP response, particularly 2 epitopes of the gamma chain, one of which is not cross reactive with ACPA. This specificity might be associated with a distinct clinical phenotype since ACa-Fib IgG were shown to be linked to systemic inflammation in very early RA but not to rapid radiological progression

Imaging for the diagnosis and follow-up of ankylosing spondylitis: development of recommendations for clinical practice based on published evidence and expert opinion.

International audienceOBJECTIVE: To develop recommendations regarding imaging studies for the diagnosis and follow-up of patients with axial forms of ankylosing spondylitis (AS) seen in everyday practice. METHODS: Evidence from the literature and expert opinion were used to develop the recommendations. Using the Delphi consensus procedure, a scientific committee selected five areas of interest, about which scientific evidence was sought by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on this evidence, a panel of experienced rheumatologists drafted recommendations, using expert opinion if needed to supplement gaps in evidence. For each recommendation, the level of evidence and the extent of agreement among the experts were specified. RESULTS: The five areas of interest dealt with the usefulness of imaging studies for the diagnosis, follow-up, prognostic evaluation, and assessment of treatment responses in patients with AS. The literature search retrieved 144 articles based on titles and abstracts. After elimination of articles that did not include an analysis of the radiological evaluation of AS, 73 articles were left for review. Eight recommendations were drafted then validated by having all panel participants vote during a final meeting. CONCLUSION: Eight recommendations about the use of imaging studies in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS

Effectiveness and safety of abatacept in elderly patients with rheumatoid arthritis enrolled in the French Society of Rheumatology’s ORA registry

International audienceOBJECTIVE:To study the effect of age on the risk-benefit balance of abatacept in RA.METHODS:Data from the French orencia and RA registry, including a 2-year follow-up, were used to compare the effectiveness and safety of abatacept according to age.RESULTS:Among the 1017 patients, 103 were very elderly (⩾75 years), 215 elderly (65-74), 406 intermediate aged (50-64) and 293 very young (<50). At baseline, elderly and very elderly patients had longer disease duration, higher CRP levels and higher disease activity. These age groups showed a lower incidence of previous anti-TNF therapy and less common concomitant use of DMARDs, but a similar use of corticosteroid therapy. After adjusting for disease duration, RF/ACPA positivity, use of DMARDs or corticosteroids and previous anti-TNF treatment, the EULAR response (good or moderate) and the remission rate were not significantly different between the four age groups. At 6 months, the very elderly had a significantly lower likelihood of a good response than the very young (odds ratio = 0.15, 95% CI: 0.03, 0.68). The decrease in DAS28-ESR over the 24-month follow-up period did not differ by age. Increasing age was associated with a higher rate of discontinuation for adverse events, especially severe infections (per 100 patient-years: 1.73 in very young, 4.65 in intermediates, 5.90 in elderly, 10.38 in very elderly; P < 0.001).CONCLUSION:The effectiveness of abatacept is not affected by age, but the increased rate of side effects, especially infections, in the elderly must be taken into account