Rheumatoid Arthritis: Daures JP

Courvoisier N, Dougados M, Cantagrel A, Goupille P, Meyer O, Sibilia J, Daures JP, Combe B. · Service de Rhumatologie, Hôpital Saint Antoine, 184 rue du Faubourg Saint Antoine, Paris, 75012, France. · Arthritis Res Ther. · Pubmed #18771585 links to  free full text

Abstract: INTRODUCTION: The objectives of this study were to determine the predictive factors of long-term radiographic outcome of rheumatoid arthritis (RA) and to describe the relationship between joint damage and disability over the course of the disease. METHODS: A cohort of 191 patients with early RA referred from primary care physicians were prospectively followed for 10 years. To determine the predictive factors of radiographic outcome, univariate analysis of the relationship between baseline values and outcome measures was undertaken using a chi-squared or Fisher's exact test. Stepwise multiple logistic regression was also performed to select independent prognostic factors. RESULTS: From data available for 112 patients, univariate analysis revealed a total Sharp score at 10 years that was significantly correlated with erythrocyte sedimentation rate (ESR), presence and level of IgA rheumatoid factor, presence of an anti-citrullinated protein antibody (ACPA), serum level of matrix metalloproteinase-3 and radiographic score at baseline. Logistic regression identified the baseline erosion score to be the most important baseline parameter as an independent prognostic factor of total radiographic score at 10 years (odds ratio = 5.64; 95% confidence interval = 1.78 to 17.86). After excluding radiographic scores from the entry parameters, the presence of ACPA and ESR were also predictive of the final total Sharp score. The Health Assessment Questionnaire (HAQ) score was strongly correlated with disease activity parameters, such as disease activity score and pain, at baseline and at three, five and 10 years. No correlation was found between total radiographic Sharp score and HAQ score throughout the study. CONCLUSIONS: In this prospective study, baseline radiographic score, ESR and ACPA were the best predictive factors of 10-year radiographic outcome in early RA. HAQ disability was associated with disease activity throughout the 10-year follow-up but not with joint damage. This discrepancy with previous reports may be due in part to the early start of therapy with disease-modifying anti-rheumatic drugs.

Maravic M, Bologna C, Daures JP, Jorgensen C, Combe B, Sany J. · Service d'Immuno-Rhumatologie, CHU Montpellier, Unité INSERM U475, France. · J Rheumatol. · Pubmed #9972956 No free full text.

Abstract: OBJECTIVE: To evaluate radiologic progression in patients with early rheumatoid arthritis (RA) receiving methotrexate (MTX) as the first slow acting drug. METHODS: An open, prospective study of 29 patients with RA (21 F, 8 M, mean age 48.5+/-15.4 yrs). The mean duration of RA was 6.6 (2-60) months; and rheumatoid factor was present in 11 cases. Clinical, biological, and radiographic evaluations were done before the start of MTX treatment and after 13+/-3.8 months. Radiographs of hands and wrists were blindly studied by 2 physicians, using Larsen's and modified Sharp's methods. There was a significant correlation for the scores of the 2 physicians evaluated by kappa coefficient. Radiographic evolution was defined as an increase of 15 points in the radiologic score by each method used. RESULTS: Patients showed significant clinical improvement after one year of MTX treatment. Despite clinical and biological improvement, significant mean radiographic progression was noted, with Larsen's method (p = 0.001) and Sharp's method (p = 0.034), without reaching the maximum score. However, using the definition of radiographic progression, the radiologic scores indicated stabilization in 23 patients with Larsen's method and in 24 patients with Sharp's method. CONCLUSION: This study revealed mild radiographic progression in early RA patients treated with MTX for one year. Further controlled studies are needed.

Lukas C, Guillemin F, Landewé R, van der Heijde D, Logeart I, Fautrel B, Daures JP, Combe B, Anonymous00090. · Immuno-Rhumatologie, Hôpital Lapeyronie, Montpellier, France. · Clin Exp Rheumatol. · Pubmed #19327234 No free full text.

Abstract: BACKGROUND: To describe the rate and timing of DMARD start in patients with early inflammatory arthritis in France, and to determine the factors leading to this treatment start. METHODS: The ESPOIR cohort study collects data on patients presenting with early arthritis. Baseline characteristics were assessed, and Cox regression analysis was performed to estimate the likelihood of starting DMARD treatment over time, adjusting for patient-, disease- and physician characteristics. RESULTS: Of the 775 analysed patients, 598 (77.2%) received at least 1 DMARD during the follow-up period, after a median time of 4.0 months. In general, a higher tender joint count, involvement of the hands, involvement of more than 3 joint groups, presence of abnormal CRP-levels or CCP-antibodies significantly increased the likelihood of being treated (p<0.01 for all determinants), as well as a positive result on the bilateral foot-squeeze test (p<0.04). In addition, a significant hetero-geneity in therapeutic strategy across the 14 tested French regions was found: adjusted hazard ratios for DMARD start ranged from 1 to 2.15 (p<0.01), depending on the region where a patient was followed. For anti-CCP test and swollen joint count we demonstrated a statistically significant interaction with geographic region, implying that these tests are interpreted differently across regions. The same factors that increased the likelihood to start a DMARD were related to an earlier start. CONCLUSION: Rate and timing of treatment start with DMARDs in patients with early inflammatory arthritis in France is determined by well known clinical and biochemical variables. Apart from these variables, however, unknown and intangible factors that seem to cluster geographically are responsible for important variations in practice performance.

Fabre S, Guisset C, Tatem L, Dossat N, Dupuy AM, Cohen JD, Cristol JP, Daures JP, Jorgensen C. · Immuno-rheumatology, Lapeyronie University Hospital, Montpellier, France. · Clin Exp Immunol. · Pubmed #19220830 No free full text.

Abstract: In rheumatoid arthritis (RA) there are currently no good indicators to predict a clinical response to rituximab. The purpose of this study was to monitor and determine the role of peripheral blood cytokine profiling in differentiating between a good versus poor response to rituximab in RA. Blood samples were collected at baseline and at 3 months from 46 RA patients who were treated with rituximab. Responders are defined by the presence of three of four American College of Rheumatology criteria: >or=20% decrease in C-reactive protein, visual analogical score of disease activity, erythrocyte sedimentation rate and improvement of the disease activity score (28) (four values) by >or=1.2 obtained at 3 months. Twelve cytokines were measured from serum collected on days 0 and 90 by proteomic array, including interleukin-6 (IL-6), tumour necrosis factor-alpha, IL-1a, IL-1b, IL-2, IL-8, interferon-gamma, IL-4, IL-10, monocyte chemoattractant protein-1, epidermal growth factor and vascular growth factor. We showed that C-reactive protein and IL-6 levels decrease significantly at 3 months in the responder group compared with baseline. At day 90 we identified a cytokine profile which differentiates responders and non-responders. High serum levels of two proinflammatory cytokines, monocyte chemoattractant protein-1 and epidermal growth factor, were significantly higher in the responder group at day 90 compared with non-responders. However, we were not able to identify a baseline cytokine profile predictive of a good response at 3 months. These findings suggest that cytokine profiling by proteomic analysis may be a promising tool for monitoring rituximab and may help in the future to identify responder RA patients.

Fabre S, Dupuy AM, Dossat N, Guisset C, Cohen JD, Cristol JP, Daures JP, Jorgensen C. · Department of Immuno-Rheumatology, Lapeyronie University Hospital, Montpellier, France. · Clin Exp Immunol. · Pubmed #18549443 links to  free full text

Abstract: In rheumatoid arthritis (RA) there are currently no useful indicators to predict a clinical response to tumour necrosis factor-alpha (TNF-alpha) blockade. The purpose of this study was to determine the role of peripheral blood cytokine profiling in differentiating between a good versus poor response to etanercept in RA. Peripheral blood samples were collected at baseline and at 3 months from 33 patients with active disease who were treated twice weekly by etanercept therapy. Responders are defined by the presence of three of four American College of Rheumatology criteria: > or =20% decrease in C-reactive protein (CRP), visual analogue score of disease activity, erythrocyte sedimentation rate and improvement of the disease activity score (28; four values) by > or =1.2 obtained at 3 months. Twelve cytokines were measured from serum collected on days 0 and 90 by proteomic array (protein biochip array, Investigator Evidence, Randox France), including interleukin (IL)-6, TNF-alpha, IL-1a, IL-1b, IL-2, IL-8, interferon-gamma, IL-4, IL-10, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF) and vascular endothelium growth factor. Our results showed that high serum levels of MCP-1 and EGF were associated with a response to etanercept. In addition, the increase of two combined parameters CRP and EGF was predictive of a response to etanercept treatment at 3 months (sensitivity: 87.5% and specificity: 75%, accuracy: 84.4%). These findings suggest that cytokine profiling by proteomic analysis before treatment initiation may help to identify a responder patient to TNF-alpha blocking agents in RA.

Cohen G, Gossec L, Dougados M, Cantagrel A, Goupille P, Daures JP, Rincheval N, Combe B. · Immuno-Rhumatologie, Montpellier I University, Centre Hospitalier Universitaire Lapeyronie, Montpellier, France. · Ann Rheum Dis. · Pubmed #16935911 No free full text.

Abstract: OBJECTIVE: To assess the radiological damage progression in patients with recent rheumatoid arthritis in sustained remission. METHODS: A cohort of 191 patients with active early (<1 year) rheumatoid arthritis was prospectively assessed at baseline, 3 and 5 years by the Disease Activity Score (DAS) and the Sharp-van der Heijde Score (SHS) for radiographic damage. Patients in remission (DAS<1.6) at the 3-year and 5-year time points were compared with patients with a persistently active rheumatoid arthritis by Wilcoxon's signed rank test. RESULTS: 57 patients died, were lost to follow-up or had incomplete data; 30 (15.7% of those who completed) patients were in remission at 3 and 5 years. The SHS in these two groups was not significantly different at baseline (p = 0.15), but was lower in the remission group at 5 years (p = 0.0047). The median (IQR) radiographic score increased from 0.5 (0-7) at baseline to 2.5 (0-14) after 5 years for the remission group (p = 0.18) and from 2 (0-7) to 13 (3-29) in the group with active rheumatoid arthritis (p<0.001). 5 (16.7%) patients in remission had relevant progression of radiographic damage (ie, progression >4.1 points) and 6 (20%) presented new erosions in a previously unaffected joint between the third and the fifth years. CONCLUSION: Patients with early rheumatoid arthritis in sustained remission did not present statistically significant radiographic degradation at the group level; nevertheless, 16.7% of these patients did present degradation. Absence of progression should be part of the remission definition in rheumatoid arthritis.

Maravic M, Bozonnat MC, Sevezan A, Gasqueres D, Pastor J, Péré M, Neil V, Roch-Bras F, Daures JP, Sany J. · Immuno-rheumatology Department, Lapeyronie Teaching Hospital, Montpellier, France. · Joint Bone Spine. · Pubmed #11143909 No free full text.

Abstract: A six-month, prospective descriptive study of medical outcomes (including quality of life) and costs was conducted in 20 incident cases of rheumatoid arthritis (RA). Multidisciplinary management was started during an inpatient stay at the beginning of the study. Patients were evaluated on a day-hospital basis three and six months later. The following parameters were studied: quality-of-life scores on a generic scale (the Nottingham Health Profile [NHP]) and two specific scales (Health Assessment Questionnaire [HAQ] and the short-form Arthritis Impact Measurement Scale [AIMS]), pain severity, disease activity assessed by the patient and physician, painful and swollen joint counts, erythrocyte sedimentation rate, and C-reactive protein level. The following costs were evaluated: laboratory tests, plain radiographs, other investigations, physician care (by rheumatologists or other specialists), second-line drug therapy and monitoring for its side effects, care by nurses, physical therapy, and occupational therapy. All patients showed significant improvement three months after initiation of multidisciplinary management. This effect was sustained through the sixth month. Quality-of-life scores improved, with the exceptions of the social isolation subscore on the NHP and the psychological impact, social activity, and occupational activity subscores on the short-form AIMS. Mean total cost for the six-month period was 3429 +/- 880 euros (1 euro = 6.6 FF). Laboratory tests contributed the largest portion of the total cost (39%), followed by rheumatologist care (16%); the other costs accounted for 7.6 to 9.2% of the total cost. This prospective medical and economic study is preliminary. Comparative studies are needed.