Academic Positions

  • Present2016

    Becomes the convener of the EULAR recommendations for gout management.

    EULAR, recommendations for gout management.

  • 20161981

    Full time physician of Hôpital Lariboisière

    Hôpital Lariboisière, Rheumatoid Arthritis

  • 19811980

    Graduated from the University of Paris Medical School 5

    University of Paris Medical School 5, Graduate School

Education & Training

  • Pr. DPresent

    Paris 7 ( Paris Diderot ) University

    Paris 7 ( Paris Diderot )

  • Dr.1989

    Lariboisière Hospital

    Lariboisière Hospital

  • Chairman1993

    ART Vigo

    ART Vigo

  • co-Director1993

    French - Vietnamese Gout and Chronic Disease Research Center

    Vien Gut

Honors, Awards and Grants

  • SCP 2014
    Distinguished Scientific Achievement Award
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  • 2012-2013
    Ormond Family Faculty Fellow
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  • June 2011
    Nautilus Silver Award for Dragonfly Effect
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  • 2000 - 2003
    Hong Kong Science International Research Grant
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  • 1999
    Citibank Best Teacher Award (school-wide award, UCLA)
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Outstanding Partner

professor of biostatistics and a recently elected member of Paris Diderot University board

Statistical analysis

Vien Gut Clinic

Patients data

University of Medicine and Pharmacy

Study protocol

Paris 7 ( Paris Diderot ) University

Research

Great Partner!

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Research Projects

  • image

    Hyperechoic deposits in the renal medulla are associated with severe gout and decreased egfr: a transversal study in 503 vietnamese patients

    1French-Vietnamese Gout Research Center, Vien Gut general clinic, Ho Chi Minh City, Viet Nam 2Rheumatology, hôpital Lariboisière, Paris, France 3Radiology, Cho Ray Hospital 4university of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam 5radiology, Hôpital Necker 6Biostatistics, hôpital Saint Louis, Paris, France

    Background: Renal medulla crystal deposits have been demonstrated by pathology in severe gout but little studied by ultrasound (US) scan.

    Objectives: To assess the frequency of hyperechoic renal medulla (HERM) in gouty patients and factors associated with their development.

    Methods: Renal US scan using a Ecube 9 echograph (Alpinion S. Korea), was performed in gout patients (ACR/EULAR criteria) consecutively seen at the Vien Gut general clinic, Ho Chi Minh City, Vietnam, and receiving no ULT at presentation. Age and sex of patients, gout features, associated diseases, serum (S) uric acid (UA), eGFR (MDRD), urinary lab stick parameters, urine UA/creatinine ratio, and fractional clearance of urate (FCU) were recorded. Patients with HERM were counted and compared with those who had no medullary deposits by the Wilcoxon rank sum test for continuous varables and the Fischer exact test for categorical variables. Multivariable logistic model was used to assess relation between variables at inclusion in the study and presence of medulla deposits.

    Results: 503 consecutive patients (500 males) were included. They had a median age of 46 years, median BMI of 25 kg/m2, median gout duration of 4 years. 280 (56%) had clinical tophi, 154 (31%) urate arthropathy, 28;56%) urolithiasis, 112 (22%) hypertension, 58 (11.5%) type 2 diabetes, 5 (1%) coronary heart disease. Their median eGFR was 78 ml/min, SUA 423 micromol/L, FCU 0.063, urine UA/creatinine ratio 0.253, urinary pH 6.

    Diffuse and bilateral HERM on the B mode with frequent twinkling artefacts on the Doppler mode was identified in 181 (36%) of the 503 patients. Univariate analysis showed that HERM associated with higher age, longer duration of gout, clinical tophi, urate arthropathy (p<0.0001 for each of the variables), higher uricemia (p=0.001), hypertension (p=0.0008), CHD (p=0.0006), lower eGFR (p<0.0001), leucocyturia (p=0.02), proteinuria (p=0.02). No association with US-diagnosed urolithiasis, hematuria, urine UA/creatinine ratio, FCU and urinary pH was found. In multivariate analysis, log of the duration of gout (0R: 2.22 (CI: 1.63–3.08), p<0.001), clinical tophi (OR: 8.21 (4.23–16.91) p<0.001), urate arthropathy (OR: 3.74 (2.18–6.52, p<0.001), and lower eGFR (OR: 0.86 (0.75–0.99) for each 10 ml/min decrease, p=0.04) were significantly associated with HERM.

    Conclusions: In our gout population, HERM was observed in 36% of patients,correlated with decreased renal function, and clearly associated with severe gout, but not with features of uric acic lithiasis.

    Disclosure of Interest: T. Bardin Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, K. M. Tran: None declared, Q. D. Nguyen: None declared, N. H. Le : None declared, P. Richette Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, P. Le Van: None declared, J.-M. Correas: None declared, M. Resche-Rigon: None declared

    DOI: 10.1136/annrheumdis-2018-eular.5027

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    Effect of serum uric acid (SUA) on gout flares (GF) and tophi resolution in gout patients. pooled post hoc analysis of clear 1 & clear 2 trials

    F. Perez-Ruiz1, P. Richette2, R.G. Karra3, I. Wild3, H. Hagedorn3, P. Kandaswamy3, T. Bardin2

    Background: Gout is caused by crystal deposition due to persistent hyperuricemia. EULAR1 and other guidelines recommend a target sUA of <5–6 mg/dL (0.30 to 0.36 mmol/L) depending on severity. Despite physiological plausibility and abundant literature evidence there is an absence of consensus among physicians on the targets and necessity of long term urate lowering therapy (ULT)2.

    Objectives: To investigate the effects of sUA and target sUA <5–6 mg/dl with respect to the occurrence of GF, flares requiring treatment (GFRT) and the percent change in the area of tophi (TR) from baseline irrespective of treatment arms.

    Methods: Data of 1213 patients (PT) was pooled from CLEAR trials3&4, two randomised, double-blind, placebo-controlled Phase 3 studies that evaluated Lesinurad 200/400 mg daily in combination with allopurinol vs allopurinol. Prophylaxis for flares was given from baseline to month (M) 5. PT who met the sUA target of <5–6 mg/dl at M 6 and 12 were compared against those not on target with respect to the TR from baseline using a Wilcoxon test. In addition, the mean sUA measurements for PT with or without GFs and GFRT was compared at M 6 and 12 using a t-test.

    Results: PT with sUA on target <5–6 mg/dl showed a larger decrease (increase in percent reduction) in area of tophi with a difference of 27.9%, and 17.3% at M 12 only compared to the PT not on target (table 1). The mean sUA levels were 0.227 mg/dL lower for PT with GF and 0.389 mg/dL lower for PT with GFRT compared to PT without GF and GFRT at M 6 (table 2), but not at M 12.

    Abstract FRI0235 – Table 1 Percent Change from baseline Area of tophi vs. SUA on target <5–6 mg/dL at M 6 and 12

    sUA (mg/dL)

    n=M6/M12

    M6

    Median (Q1, Q3)

    p-value#

    M12

    Median (Q1, Q3)

    p-value#

    <5 (n=31/36)

    −22.1 (-46.4, 5.63)

    0.78

    −59.6 (-98.3,–27.5)

    0.01

    ≥5 (n=93/87)

    −22–2 (-56.7, 6.91)

    −31.7 (-77.4, 13.06)

     

    <6 (n=63/66)

    −23.8 (-56.7, 1.59)

    0.64

    −49.0 (-93.3,–12.9)

    0.06

    ≥6 (n=61/57)

    −19.2 (-42.5, 10.30)

    −31.7 (-60.1, 13.06)

     

    § Number of PT with a target tophus at baseline was small. # Wilcoxon test with H0: Mean ranks in categories are equal

    Abstract FRI0235 – Table 2 Mean sUA at M 6 and 12 by occurrence of GF and GFRT

    Mean sUA mg/dL (95% CI) M6

    p-value#

    Mean sUA (95% CI) M12

    p-value#

    GF Yes

    5.94 (5.80–6.07)

     

    5.92 (5.79–6.06)

     

    GF No

    5.71 (5.51–5.92)

     

    5.91 (5.64–6.17)

     

    Difference

    0.22 (−0.01–0.47)

    0.06

    0.01 (−0.28–0.31)

    0.91

    GFRT No

    5.91 (5.79–6.03)

     

    5.93 (5.80–6.05)

     

    GFRT Yes

    5.530 (5.23–5.83)

     

    5.83 (5,41–6.25)

     

    Difference

    0.38 (0.06–0.71)

    0.01

    0.09 (−0.34–0.53)

    0.65

    # T-test with H0: No difference in means

    Conclusions: These results confirm that sUA on target <5–6 mg/dl is essential for TR, and longer the control better the TR. The lower mean sUA levels for PT with GF and GFRT was observed at M6 and not at M 12, maybe owing to the fact that flares are common during the first months of ULT initiation and then taper off and urate deposits were more fragile and not completely dissolved. Also M 6 and 12 may not be optimal to observe statistically significant differences between treatments with respect to TR, GF and GFRT.

    References:

    1. Richette P, et al. Ann Rheum Dis 2017;76:29−42.
    2. Qaseem A, et al. Ann Intern Med 2017;166(1):58–68.
    3. Saag KG, et al. Arthritis Rheumatol 2017;69:203–12.
    4. Bardin T, et al. Ann Rheum Dis 2017;76:811–20.

    Disclosure of Interest: F. Perez-Ruiz Consultant for: Grünenthal, Menarini, Speakers bureau: Grünenthal, Menarini, P. Richette Consultant for: Grünenthal, Speakers bureau: Grünenthal, R. Karra Employee of: Grünenthal, I. Wild Employee of: Grünenthal, H. Hagedorn Employee of: Grünenthal, P. Kandaswamy Employee of: Grünenthal, T. Bardin Consultant for: Grünenthal

    DOI: 10.1136/annrheumdis-2018-eular.5565

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    Elevated levels of il-37 are associated with tophus and suppressed the production of inflammatory cytokines in patients with gout

    X. Hong, L. Ding, Q. Huang, D. Liu

    Background: IL-37 has been identified as a natural inhibitor of innate immunity. Although increasing evidence shows elevated IL-37 expression in various autoimmune diseases, its correlation with clinical symptoms in gout is still unclear.

    Objectives: This study aims to determine the correlation between the levels of IL-37 and clinical indexes in gout patients, and to examine the inhibitory effect of IL-37 on pro-inflammatory cytokine including IL-1β, IL-6 and IL-18 from peripheral blood mononuclear cells (PBMC) of gout patients in culture.

    Methods: Levels of serum IL-37 and concentrations of IL-1β, IL-6, IL-18 in cell culture from 42 patients with gout and 40 healthy controls (HCs) were measured by enzyme-linked immunoassay (ELISA). Moreover, the relative mRNA expression of these cytokines in PBMCs was detected by real-time PCR (RT-PCR). The correlations between serum IL-37 levels and clinical values in gout patients were analysed by Spearman correlation test.

    Results: Both protein and mRNA levels of IL-37 were higher in gout patients than healthy controls, especially in patients with tophus. Serum IL-37 levels of gout patients were positively correlated with C-reactive protein and uric acid. Furthermore, the expression of IL-1β, IL-6 and IL-18 in PBMCs from gout patients was significantly increased, which were markedly suppressed by IL-37 in culture.

    Abstract AB0084 – Figure 1IL-37 suppresses the expression of pro-inflammatory cytokines in PBMCs from gout patients

    abs_ZRQQQQRY_F001.jpg

    Conclusions: Serum levels of IL-37 are closely associated with clinical symptoms in gout patients and may represent a potential biomarker for the disease activity.

    References:

    1. Richette P, Bardin T. Gout. Lancet 2010;375(9711)318–28.
    2. Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009;27(2009)621–68.
    3. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006;440(7081)237–41.
    4. Emmerson BT. The management of gout. N Engl J Med, 1996;334(7)445–51.
    5. Fiechtner JJ, Simkin PA. Urate spherulites in gouty synovia. JAMA 1981;245(15)1533–6.

    Disclosure of Interest: None declared

    DOI: 10.1136/annrheumdis-2018-eular.2269

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    Estimating health-related quality of life for gout patients: a post-hoc analysis of utilities from the clear trials

    F. Pérez-Ruiz1, A. So2, P. Kandaswamy3, R. Karra3, K. Kelton4, S. Perk4, T. Bardin5

    Background: Prior studies of health-related quality of life (HRQoL) in gout patients have shown significant disutilities associated with flares and tophi or serum uric acid (sUA).1 2 However, no prior study has explored the simultaneous impact of all three aspects of gout severity.

    Objectives: Estimate the impact of gout flares, tophi, and sUA levels on HRQoL through post-hoc analysis of SF-36 data collected in two randomised, double-blind, placebo-controlled Phase 3 studies of urate lowering therapies in gout patients (CLEAR 1 and CLEAR 2).3 4

    Methods: Linear regression analysis was used to estimate the effects of patient and disease characteristics on SF-6D scores at month 6 and month 12. Multiple regression methods and out-of-sample testing were used to select the final model from covariates representing tophus burden, the number of flares during each six-month period, serum urate levels, baseline characteristics, and comorbidities. Predicted mean utility scores were calculated by evaluating the model at the mean values of the covariates (excluding location-specific covariates) in the pooled CLEAR 1 and CLEAR 2 intent-to-treat population.3 4

    Results: The final regression model (table 1) includes significant disutilities associated with the presence of tophi at screening (0.0418; SE: 0.0073; p<0.001), the number of gout flares (0.0036 per flare; SE: 0.0005; p<0.001), and median sUA on-treatment (0.0083 per mg/dL in excess of 6 mg/dL; SE: 0.0031; p=0.007). The predicted mean utility scores for patients with zero flares and no tophi are 0.7718 for sUA <6 mg/dL; 0.7552 for sUA 6 to <8 mg/dL; 0.7386 for sUA 8 to <10 mg/dL; and 0.7220 for sUA ≥10 mg/dL.

    Abstract OP0162HPR – Table 1 Regression model of SF-6D utilities

    Coefficient

    Mean

    SE

    p value

    Intercept

    0.9182

    0.0235

    <0.001

    Region Europe

    –0.0641

    0.0092

    <0.001

    Country New Zealand

    0.0523

    0.0200

    0.009

    Age

    –0.0009

    0.0003

    0.003

    Female

    –0.0242

    0.0140

    0.084

    Black race

    –0.0307

    0.0098

    0.002

    Body mass index

    –0.0020

    0.0005

    <0.001

    Diabetes mellitus

    –0.0215

    0.0080

    0.007

    Hypertension

    –0.0172

    0.0067

    0.010

    Unemployed

    –0.0596

    0.0103

    <0.001

    Disabled or retired due to illness

    –0.1125

    0.0121

    <0.001

    Number of gout flares

    –0.0036

    0.0005

    <0.001

    Tophi present at screening

    –0.0418

    0.0073

    <0.001

    sUA per mg/dL in excess of 6 mg/dL

    –0.0083

    0.0031

    0.007

    R2: 0.1788; Adjusted R2: 0.1730; Residual standard error: 0.1217 on 1857 degrees of freedom. Baseline characteristics. Median sUA on-treatment. Abbreviations: SE, standard error; SF-6D, Short form 6D questionnaire; sUA, serum uric acid.

    Conclusions: The present analysis is unique in that it explored the simultaneous effects of flares, tophi, and sUA on HRQoL. The results indicate that high sUA levels are associated with significant disutility when controlling for the effects of flares, tophi, and other patient covariates. The clinical rationale is that uncontrolled sUA creates a state of chronic inflammation, contributing to underlying ill health in addition to its effects on flares, tophi, and comorbidities.

    References

    1. Beard SM, et al. Eur J Health Econ 2014;15(5):453–63.
    2. Khanna PP, et al. Health Qual Life Outcomes 2012;10:117.
    3. Data on file. Clinical Study Report RDEA594–301. Ardea Biosciences, Inc.; 2014.
    4. Data on file. Clinical Study Report RDEA594–302. Ardea Biosciences, Inc.; 2014.

    Disclosure of Interest: F. Pérez-Ruiz Grant/research support from: Spanish Society of Rheumatology, Cruces Hospital Rheumatology Association, Consultant for: Grünenthal, Menarini, Speakers bureau: Grünenthal, Menarini, A. So Consultant for: Grünenthal, Sobi, Speakers bureau: Grünenthal, Sobi, P. Kandaswamy Employee of: Grünenthal, R. Karra Employee of: Grünenthal, K. Kelton Employee of: Medical Decision Modelling, a contractor to Grünenthal, S. Perk Employee of: Medical Decision Modelling, a contractor to Grünenthal, T. Bardin Consultant for: Grünenthal, AstraZenaca, Menarini, Ipsen, Sobi, Novartis

    DOI: 10.1136/annrheumdis-2018-eular.6822

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    Hyperechoic deposits in the renal medulla are associated with severe gout and decreased egfr: a transversal study in 503 vietnamese patients

    T. Bardin1,2, K.M. Tran1, Q.D. Nguyen1, N.H. Le1, P. Richette2, P. Le Van3,4, J.-M. Correas5, M. Resche-Rigon6

    Background: Renal medulla crystal deposits have been demonstrated by pathology in severe gout but little studied by ultrasound (US) scan.

    Objectives: To assess the frequency of hyperechoic renal medulla (HERM) in gouty patients and factors associated with their development.

    Methods: Renal US scan using a Ecube 9 echograph (Alpinion S. Korea), was performed in gout patients (ACR/EULAR criteria) consecutively seen at the Vien Gut general clinic, Ho Chi Minh City, Vietnam, and receiving no ULT at presentation. Age and sex of patients, gout features, associated diseases, serum (S) uric acid (UA), eGFR (MDRD), urinary lab stick parameters, urine UA/creatinine ratio, and fractional clearance of urate (FCU) were recorded. Patients with HERM were counted and compared with those who had no medullary deposits by the Wilcoxon rank sum test for continuous varables and the Fischer exact test for categorical variables. Multivariable logistic model was used to assess relation between variables at inclusion in the study and presence of medulla deposits.

    Results: 503 consecutive patients (500 males) were included. They had a median age of 46 years, median BMI of 25 kg/m2, median gout duration of 4 years. 280 (56%) had clinical tophi, 154 (31%) urate arthropathy, 28;56%) urolithiasis, 112 (22%) hypertension, 58 (11.5%) type 2 diabetes, 5 (1%) coronary heart disease. Their median eGFR was 78 ml/min, SUA 423 micromol/L, FCU 0.063, urine UA/creatinine ratio 0.253, urinary pH 6.

    Diffuse and bilateral HERM on the B mode with frequent twinkling artefacts on the Doppler mode was identified in 181 (36%) of the 503 patients. Univariate analysis showed that HERM associated with higher age, longer duration of gout, clinical tophi, urate arthropathy (p<0.0001 for each of the variables), higher uricemia (p=0.001), hypertension (p=0.0008), CHD (p=0.0006), lower eGFR (p<0.0001), leucocyturia (p=0.02), proteinuria (p=0.02). No association with US-diagnosed urolithiasis, hematuria, urine UA/creatinine ratio, FCU and urinary pH was found. In multivariate analysis, log of the duration of gout (0R: 2.22 (CI: 1.63–3.08), p<0.001), clinical tophi (OR: 8.21 (4.23–16.91) p<0.001), urate arthropathy (OR: 3.74 (2.18–6.52, p<0.001), and lower eGFR (OR: 0.86 (0.75–0.99) for each 10 ml/min decrease, p=0.04) were significantly associated with HERM.

    Conclusions: In our gout population, HERM was observed in 36% of patients,correlated with decreased renal function, and clearly associated with severe gout, but not with features of uric acic lithiasis.

    Disclosure of Interest: T. Bardin Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, K. M. Tran: None declared, Q. D. Nguyen: None declared, N. H. Le : None declared, P. Richette Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, P. Le Van: None declared, J.-M. Correas: None declared, M. Resche-Rigon: None declared

    DOI: 10.1136/annrheumdis-2018-eular.5027

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    Lesinurad (LESU) adjunctive therapy with allopurinol (ALLO) in patients not responding to allo monotherapy: pooled post hoc safety and efficacy analysis in a patient subgroup using concomitant diuretics at baseline (BL)

    T. Bardin1, R.G. Karra2, A. So3, A.-K. Tausche4, I. Wild2, H. Hagedorn2, P. Kandaswamy2, F. Perez-Ruiz5

    Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.

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    Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.

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    What are gout guidelines good for ?

    T. Bardin

    Guidelines aim to help physicians to make decisions in daily practice for an individual patient with a given condition. Guidelines should therefore be clear, easily readable and understandable by all physicians involved in disease care. They should also be as simple and brief as possible to be easily memorised by physicians, and this is a real challenge when guidelines aim at a full coverage of gout management. Most importantly, they cannot be taken as strict rules with legal implications. The final decisions concerning an individual patient remain in the hands of the responsible physician.

    Guideline methodology has improved over years but still varies across recently published works. Ad hoc committees regularly involve all specialities involved in the disease care, and in the case of gout, general practitioners, who take care of most gout patients are now included but their number vary. Patients are not always included, despite being the final target of guidelines. Conflicts of interest of participating physicians are taken into account to a varying extent. The guideline development process involves an evaluation of all evidence available at the time of writing. Treatment impact on outcome, and assessment of drug benefit ratios are unanimously considered as important in the elaboration of guidelines. Factors such as drug pricing, availability and local regulatory agency recommendations, for instance about reimbursement, also matter, as guidelines should be practical in order to help physicians, but are rarely taken into account in guidelines.

    There are several levels of evidence and the best ones, such as randomised placebo-controlled trials (RCT) or RCT meta-analyses are not available in all aspects of gout management. A large part of the published guidelines on the management of gout therefore relies on expert opinion, which remains fragile and may vary from one group to the other.

    The numerous guidelines presently available for gout management exhibit more or less striking differences, and this diversity does not help guidelines to reach their goal. In this regard, the major differences observed between the simple and short guidelines issued by the American College of Physicians and the usually more complicated recommendations from the Rheumatology societies are the most detrimental. Pursuing therapeutic research on gout management and improving guideline methodology appear as sine qua non conditions to reach consensus and improve gout management.

    Disclosure of Interest: T. Bardin Consultant for: astraZeneka, ipsen menarini, novartis

    DOI: 10.1136/annrheumdis-2018-eular.7823

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    A PROOF-OF-CONCEPT STUDY: TREATING TO THE TARGET WITH URATE LOWERING THERAPY IN REAL-WORLD GOUT PATIENTS

    C.A. Janssen1, T.L. Jansen2, M.A. Oude Voshaar1, H.E. Vonkeman1, M.A. van de Laar1

    Background: Gouty arthritis is a common, potentially disabling and increasingly prevalent disease [1]. Last year, the European League Against Rheumatism (EULAR) task force gout updated the 2006 recommendations for the management of gout [2,3]. The guideline stresses the application of a targeted approach when initiating urate lowering therapy (ULT) in gout patients for reaching the recommended serum urate (sUA) target values. However, data on clinical outcomes of real-world gout patients treated according to this approach are limited.

    Objectives: To examine the clinical outcomes achieved in two patient cohorts in which differing targeted ULT treatment approaches were employed, both aiming to reach the EULAR recommended sUA targets.

    Methods: We conducted a retrospective chart review study. Gout patients were included that had been treated at the rheumatology departments of two clinical centers in the Netherlands, applying different targeted ULT treatment approaches. Patients in cohort A followed an approach combining two modes of action once allopurinol monotherapy failed to reach the predefined target, whereas patients in cohort B were treated with sequential monotherapy following allopurinol monotherapy failure. Outcome parameters were defined to reflect the EULAR recommendations concerning ULT [3].

    Results: A total of 177 patients were included in the study; 99 in cohort A and 78 in cohort B. The majority (N=146, 82.5%) of the included patients from both cohorts were able to meet the predefined sUA target of <360 μmol/L. In addition, more than half (N=104, 58.8%) of the patients reached the stringent sUA target of <300 μmol/L. The proportion of patients reaching sUA targets did not differ significantly (p=0.51) between the cohorts, with 80.8% (n=80) of the patients in cohort A reaching the primary sUA target, compared to 85.7% (n=66) in cohort B (Figure 1). In total, patients following treatment with first-line allopurinol, second-line monotherapy options or second-line combination therapy, 102/124 (82.3%), 25/31 (80.6%) and 19/21 (90.5%) respectively, reached the primary sUA target.

     

     

    Conclusions: This chart review provides a proof-of-concept of the treat-to-target approach in gout patients when a targeted approach with ULT is applied. However, our study also shows that not all patients may reach targets using currently available treatment options. Prospective, pragmatic randomized studies to investigate differences between specific treatment regimes in gout patients, together with costs, safety and patient-reported outcome measures are needed.

    References:

     

     

    Kuo C-F, Grainge MJ, Zhang W, et al. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 2015;11:649–62. doi:10.1038/nrrheum.2015.91.

     

    Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006;65:1312–24. doi:10.1136/ard.2006.055269.

     

    Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76:29–42. doi:10.1136/annrheumdis-2016–209707.

    Disclosure of Interest: None declared

    DOI: 10.1136/annrheumdis-2017-eular.2377

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    ACCURACY OF HUMASENS-PLUS POINT-OF-CARE URIC ACID METER USING CAPILLARY BLOOD OBTAINED BY FINGERTIP PUNCTURE

    S. Fabre1, P. Clerson2, J.-M. Launay3, J.-F. Gautier4, T. Vidal-Trecan4, J.-P. Riveline4, A. Platt5, A. Abrahamsson6, J.N. Miner7, G. Hughes5, P. Richette1, T. Bardin1

    Background: A key factor in the success of gout management is the long-term lowering of uricemia below predetermined targets (300 or 360μ mol/l). Monitoring of uricemia in gout patients is therefore important, and is presently done in the laboratory on plasma samples obtained after venous puncture. An accurate uric acid (UA) meter allowing rapid testing by the health care professionals and self-measurement by the patient should improve management of gout.

    Objectives: This study aimed to assess the reliability of immediate UA measurement in capillary blood samples obtained from fingertip puncture using the HumaSensPlus point-of-care meter (meter) compared with that of a standard laboratory assay (lab).

    Methods: Capillary UA levels were measured from 236 consenting diabetic patients using the commercially available HumaSensPlus UA meter (European Conformity marked and approved for EU market use). Each patient also had a plasma UA measurement in the biochemistry laboratory using an uricase automated colorimetric assay. Since the UA meter has a dynamic range of 180–1190μ mol/l, when the values were out-ranged (meter reading LO or HI), they were individually compared to corresponding plasma measurements. Agreement between capillary and plasma UA levels was assessed by Intraclass Correlation Coefficient (ICC) and Bland-Altman graphic representation. Best capillary UA threshold for detection of hyperuricemia (plasma UA>360μmol/l) was determined from a ROC curve, relationship between methods were identified by regression. Impact of potential confounding factors (biological parameters/treatments) was searched. A total of 206 paired measurements were required for estimation of an ICC of 0.80 with a precision of 0.10 at alpha risk of 0.05%. To better understand discrepancies between meter and lab, results were compared to reference plasma UA measurements by liquid chromatography-mass spectrometry (LC-MS) in a subgroup of 77 patients who gave complementary consent.

    Results: Fourteen capillary samples were read LO by the meter: 11 were confirmed by lab to be below 180μmol/l and 3 were above (189, 206 and 428μmol/l). Two capillary samples were read HI and were measured at 303 and 213μmol/l by lab. In the remaining 222 samples with meter and lab values, ICC was 0.90 [0.87–0.92] and Bland-Altman curve showed acceptable agreement over all the tested values. Best meter threshold for detection of hyperuricemia by the HumaSensPlus meter was 330μmol/l (sensitivity 0.89, specificity 0.89, area under the ROC curve 0.95). Based on regression, plasma uricase of 360μmol/l corresponded to 343μmol/l. Among the biological parameters tested, only hematocrit impacted capillary uric acid measurements, however negligibly. No medication appeared to significantly affect test results. Plasma uricase measurements were better correlated to LC-MS measurements (r=0.98 [0.96–0.99]) than capillary measurements (r=0.84 [0.75–0.90]).

    Conclusions: Results of the HumaSensPlus meter were reasonably comparable to those of the laboratory assay. It is easy to use and may be useful in clinic and in epidemiologic studies.

    Disclosure of Interest: None declared

    DOI: 10.1136/annrheumdis-2017-eular.2787

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    DO WE CONTROL GOUT IN PRIMARY CARE FOLLOWING EULAR RECOMMENDATIONS?

    F. Leon Vazquez1, C. Sanz Rodrigo2, C. Muñoz Martínez de Salinas2, M. Ferruelo Magán2, M. Metola Gόmez2, A. Del Caño Garrido1, C. González Fernández2

    Background: Inadequate control of hyperuricaemia in gout patients can lead to more arthritis, activity limitations and higher gout-related treatment costs. General Practitioners can use well tolerated urate-lowering drugs, but some patients are inadequately controlled. European League against Rheumatism (EULAR) has published new guidelines1 in 2016 with similar serum Uric Acid (sUA) goals.

    Objectives: To evaluate sUA control in patients diagnosed with gout who were attended in primary care and to compare them to EULAR 2016 guidelines1.

    Methods: Retrospective analysis, carried out in 2 primary care health centres (8 family doctors) in Spain. We selected patients that have consulted in the last year diagnosed with gout at any time. Demographic variables, gout-related drugs and last sUA level were collected. Adequate control was defined as sUA level <6 mg/dL.

    Limitations: We used only one isolated sUA value. No drug doses were analyzed. We did not distinguish severe from mild gout.

    Ethical-legal aspects: We did not identify the patients. There was no intervention.

    Results: We analyzed 231 patients diagnosed with gout, mean 70.1 years-old (Confidence Interval CI95% 68.3–72.0), 189 (81.8%) were men. The mean sUA was 6.55 mg/dL (CI95% 6.31–6.79 mg/dL).

    39% were adequately controlled according to EULAR (sUA <6 mg/dL), 25.5% were close to the objective (6–7mg/dL) and clearly inadequate (>7mg/dL) in 35.5%. 10% had really bad control (sUA >9 mg/dL).

    There was no difference between control in male 6.58 mg/dL (IC95% 6.33–6.83) and female 6.40 mg/dL (CI95% 5.73–7.07). Control improves in elder people: <60 years 7.01 mg/dL (CI95% 6.60–7.42) vs.>70 years 6.30 mg/dL (CI95% 6.00–6.60)

    The only 14 patients receiving febuxostat achieved similar control using allopurinol (6.5 versus 6.7 mg/dL).

    Conclusions: The degree of control of sUA in primary care patients in our area is mostly between optimal and acceptable, but it can be optimized in more than half of the cases. In a few patients the control is lousy. The worst-controlled patients were the youngest.

    References:

     

     

    Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J, Coyfish M, Guillo S, Jansen TL, Janssens H, Lioté F, Mallen C, Nuki G, Perez-Ruiz F, Pimentao J, Punzi L, Pywell T, So A, Tausche AK, Uhlig T, Zavada J, Zhang W, Tubach F, Bardin T. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017 Jan;76(1):29–42. http://ard.bmj.com/content/76/1/29.abstract.

    Disclosure of Interest: None declared

    DOI: 10.1136/annrheumdis-2017-eular.6961

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    Urate lowering to ACR-recommended targets allows significant improvement of severe gout. A monocentric experience in Vietnam, using a systematic treatment protocol

    Thomas Bardin1,2, Quang Nguyen Dinh1, Khoi Tran Minh1, Nghia Le Hieu1, Minh Duc3, Pascal Richette1, Matthieu Resche-Riggon2

    1 French – Vietnamese Research Center on Gout, Ho Chi Minh City, Vietnam - 2 University Paris Diderot, France - 3 University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

    Rheumatology

    Background: Gout is frequent and severe in Vietnam, where urate-lowering drugs (ULD) are seldom used and many patients are treated by traditional herbal medicine. We looked at the effect of a T2T strategy using allopurinol on severe Vietnamese gout.

    Methods: 100 Vietnamese, ULD- free, crystal-proven gout patients (99 M, 1 F) with a eGFR > 60 ml/min, were prospectively followed after allopurinol introduction. The median age of patients was 47 years, median disease duration 10 years, median BMI 25 kg/m2; 91 patients had multiple clinical tophi, 32 had hypertension, 7 type 2 diabetes, 31 dyslipidemia, 47 coronary heart disease, 16 were on long term steroid. Treatment protocol included fullpatient information, titration of allopurinol up to obtaining a predefined SUA target (6 mg/dL in 5 patients and 5 mg/dL in 95), flare prophylaxis by colchicine (0.5 to 1mg/d) during the first months, and traditional herbal medicine. At each visit, gout flares from the last visit were counted using a daily diary, palpable tophus size was assessed using a Vernier caliper, SUA and eGFR were determined. Ultrasound (US) scan was performed at inclusion and every 3 months and allowed search for double contour (DC) at the knees and MTPs -which were found in all patients at baseline and classified into 4 classes (thick, medium, thin and none)- and measurement of a hand or foot index tophus. Quality of life (gout impact scale (GIS) and function were recorded at inclusion and after 12 months. The effect of SUA lowering was explored by comparing inclusion and 12-month data, in patients who reached the SUA targets and those who did not, using standard statistics.

     

     

    Background: Gout is frequent and severe in Vietnam, where urate-lowering drugs (ULD) are seldom used and many patients are treated by traditional herbal medicine. We looked at the effect of a T2T strategy using allopurinol on severe Vietnamese gout.

    Methods: 100 Vietnamese, ULD- free, crystal-proven gout patients (99 M, 1 F) with a eGFR > 60 ml/min, were prospectively followed after allopurinol introduction. The median age of patients was 47 years, median disease duration 10 years, median BMI 25 kg/m2; 91 patients had multiple clinical tophi, 32 had hypertension, 7 type 2 diabetes, 31 dyslipidemia, 47 coronary heart disease, 16 were on long term steroid. Treatment protocol included fullpatient information, titration of allopurinol up to obtaining a predefined SUA target (6 mg/dL in 5 patients and 5 mg/dL in 95), flare prophylaxis by colchicine (0.5 to 1mg/d) during the first months, and traditional herbal medicine. At each visit, gout flares from the last visit were counted using a daily diary, palpable tophus size was assessed using a Vernier caliper, SUA and eGFR were determined. Ultrasound (US) scan was performed at inclusion and every 3 months and allowed search for double contour (DC) at the knees and MTPs -which were found in all patients at baseline and classified into 4 classes (thick, medium, thin and none)- and measurement of a hand or foot index tophus. Quality of life (gout impact scale (GIS) and function were recorded at inclusion and after 12 months. The effect of SUA lowering was explored by comparing inclusion and 12-month data, in patients who reached the SUA targets and those who did not, using standard statistics.

    Results: 84 and 68 patients were seen at 6 and 12 months, respectively. Reasons for loss of follow-up were major improvement (12), alcoholism (2), long distance from the center (8), intercurrent disease or personal problem (9), and intolerance to allopurinol (4). The mean maximal dose of allopurinol was 520 (+165) mg/d and was reached after a median of 2 (+1.3) months. SUA target was obtained in 89 patients. Mean flare rate per month significantly declined from 2.5 on M1 (n=98) to 1.1 at M6 (n=84) (p<0.001), and 0.15 at M12 (n=68) (p<0.001), at a time when all patients were free of prophylactic colchicine, NSAIDs or steroid but remained under herbal treatment, with no significant difference between patients who were or were not at SUA targets. GIS significantly similarly strongly improved in all dimensions (p<0.02) except fear of side effects (p=0.13) and did not correlate with SUA target. Function significantly (p<0.004) improved, and even more in patients at target (p<0.001). Tophi (p<0.001 for both caliper and US measurements) and DC (p<0.03 for all locations) significantly decreased between inclusion and M12 and both decreases correlated with achievement of SUA target (p=0.004 for tophi, and <0.03 for DC disappearance).

    Conclusion: The T2T strategy strikingly improved patients. Tophi and DCs decreased, and function improved in correlation with achievement of SUA target. Flare rate dramatically decreased and GIS strongly improved but these did not correlate with SUA target achievement, suggesting anti-inflammatory effect of high dose allopurinol and/or herbal medicine.

    Introduction

    • The Vien Gut Medical center, in Ho Chi Minh City, Vietnam (VN) has been exclusively devoted to gout care for 10 years. An average of 4,000 gouty patients have been seen every  year.

    • About 1/3 of patients seen at the Vien Gut clinic suffer from severe, tophaceous gout (figure 1).

    • Up to 2015, gout was treated in this center by traditionnal, herbal medicine only.

    • In 2015 we introduced the use of urate-lowering drugs (ULDs) and decided to perform a prospective study of the effects of this therapeutic strategy

    Study Design

    • 100 patients were included in the study

    • Inclusion criteria:

    • Crystal proven gout

    • eGFR > 60 ml/min

    • Oral consentment to participate

    • The treatment protocol combined:

    • Allopurinol titration up to reaching the ACR and EULAR-recommended serum  uric acid (SUA) targets

    • Prophylactic colchicine (0.5-1mg/d) during the first months

    • Full education, repeated at each visit

    •Traditional herbal medicine treatment

    • Duration of the study: one year

    • Ethic committe approval:  
    University of Medicine and Pharmacy at Ho Chi Minh City (VN),

      Approval number: 198 of the year 2017

    Data Recording at Inclusion

    •Full medical history and physical examination

    •Number of fares in the preceding year

    •Assessment of urate arthropathies

    •Chart and count of clinical tophi

    •Vernier calliper measurement of 1 index tophus (hands or feet)

    •Digital photographs of hands and feet

    •Diet assesment, including alcohol and soda intake

    •ECG

    •Ultrasound (US) scan of MTPs, knees, liver, kidneys

    •Assesment of double contours (DC) according to 4 grades (fig 2) and measurement of an index tophus

    •Radiographs of urate arthropathies

    •Biological tests: SUA, eGFR (MDRD), FCU, CBC, CRP,  lipids, fasting glucose, CK, liver enzymes, urinary pH

    Prospective Follow-up Protocol

    - Patients were seen every month until the target uricemia was reached (< 6mg/L, or 5mg/L in patients with tophi or frequent flares (> 6/y), then at least at M3,6,9 and 12.

    - They filled out a diary, that included VAS for every joint and daily intake of drugs (fig 6)

    - At each visit

    •Patient weight, BP, pulse, any intercurrent illness were recorded

    •The number of flares was counted according to the diary information. Patients were instructed to automedicate early in case of flares. These were defined as an increase of joint VAS + NSAID, steroid or increased colchicine intake.

    •Digital photographs were taken of the hands and feet (Fig 3)

    •1 index hand/foot tophus was measured

    •SUA, eGFR, fasting glucose, CBC,  liver enzymes, CK, urine pH, FCU were measured

    •The number of remaining tablets were counted to assess drug adherence and diary coherence (all drugs were delivered by the Vien Gut pharmacy)

    - Supplementary data obtained at the M6 and M12 visits

    •Diet assessment

    •Gout impact scale

    •Function

    •US scan of the knees and feet

    •Double contour grading

    •Index tophus measurement

    •US scan of the liver

    •US scan of the kidney

    •Radiographs of the urate
    arthropathy-involved joints (Fig 4)

    •Blood lipid measurement

    Statistical Methods

    •Quantitative variables are described by their mean (SD) or median [Interquartile range]

    •Qualitative variables are described by their count and percentage

    •Tests between groups for qualitative variables were performed using Fisher test and McNemar test for paired data

    •Tests between groups for quantitative variables were performed using Wilcoxon test and Wilcoxon paired test for paired data

    •Correlation between measurements and target achievement of SUA at M3 were evaluated using random effect linear models.

    Results

     

     

    Effect of serum uric acid (SUA) on gout flares (GF) and tophi resolution in gout patients. pooled post hoc analysis of clear 1 & clear 2 trials

    F. Perez-Ruiz1, P. Richette2, R.G. Karra3, I. Wild3, H. Hagedorn3, P. Kandaswamy3, T. Bardin2

    1. Rheumatology Division of Cruces Hospital and University of the Basque Country, Baracaldo, Spain
    2. Université Paris Diderot, Paris, France
    3. Grünenthal GmbH, Aachen, Germany
    Rheumatology Division

    1Rheumatology Division of Cruces Hospital and University of the Basque Country, Baracaldo, Spain 2Université Paris Diderot, Paris, France 3Grünenthal GmbH, Aachen, Germany

    Effect of serum uric acid (SUA) on gout flares (GF) and tophi resolution in gout patients. pooled post hoc analysis of clear 1 & clear 2 trials

    Background Gout is caused by crystal deposition due to persistent hyperuricemia. EULAR1 and other guidelines recommend a target sUA of <5–6 mg/dL (0.30 to 0.36 mmol/L) depending on severity. Despite physiological plausibility and abundant literature evidence there is an absence of consensus among physicians on the targets and necessity of long term urate lowering therapy (ULT)2.

    Objectives To investigate the effects of sUA and target sUA <5–6 mg/dl with respect to the occurrence of GF, flares requiring treatment (GFRT) and the percent change in the area of tophi (TR) from baseline irrespective of treatment arms.

    Methods Data of 1213 patients (PT) was pooled from CLEAR trials3&4, two randomised, double-blind, placebo-controlled Phase 3 studies that evaluated Lesinurad 200/400 mg daily in combination with allopurinol vs allopurinol. Prophylaxis for flares was given from baseline to month (M) 5. PT who met the sUA target of <5–6 mg/dl at M 6 and 12 were compared against those not on target with respect to the TR from baseline using a Wilcoxon test. In addition, the mean sUA measurements for PT with or without GFs and GFRT was compared at M 6 and 12 using a t-test.

    Results PT with sUA on target <5–6 mg/dl showed a larger decrease (increase in percent reduction) in area of tophi with a difference of 27.9%, and 17.3% at M 12 only compared to the PT not on target (table 1). The mean sUA levels were 0.227 mg/dL lower for PT with GF and 0.389 mg/dL lower for PT with GFRT compared to PT without GF and GFRT at M 6 (table 2), but not at M 12.

    Conclusions These results confirm that sUA on target <5–6 mg/dl is essential for TR, and longer the control better the TR. The lower mean sUA levels for PT with GF and GFRT was observed at M6 and not at M 12, maybe owing to the fact that flares are common during the first months of ULT initiation and then taper off and urate deposits were more fragile and not completely dissolved. Also M 6 and 12 may not be optimal to observe statistically significant differences between treatments with respect to TR, GF and GFRT.

    References [1] Richette P, et al. Ann Rheum Dis 2017;76:29−42.

    [2] Qaseem A, et al. Ann Intern Med2017;166(1):58–68.

    [3] Saag KG, et al. Arthritis Rheumatol2017;69:203–12.

    [4] Bardin T, et al. Ann Rheum Dis2017;76:811–20.

    Disclosure of Interest F. Perez-Ruiz Consultant for: Grünenthal, Menarini, Speakers bureau: Grünenthal, Menarini, P. Richette Consultant for: Grünenthal, Speakers bureau: Grünenthal, R. Karra Employee of: Grünenthal, I. Wild Employee of: Grünenthal, H. Hagedorn Employee of: Grünenthal, P. Kandaswamy Employee of: Grünenthal, T. Bardin Consultant for: Grünenthal

    http://dx.doi.org/10.1136/annrheumdis-2018-eular.5565

     

    Hyperechoic deposits in the renal medulla are associated with severe gout and decreased egfr: a transversal study in 503 vietnamese patients

    T. Bardin1,2, K.M. Tran1, Q.D. Nguyen1, N.H. Le1, P. Richette2, P. Le Van3,4, J.-M. Correas5, M. Resche-Rigon6

    1. French-Vietnamese Gout Research Center, Vien Gut general clinic, Ho Chi Minh City, Viet Nam
    2. Rheumatology, hôpital Lariboisière, Paris, France
    3. Radiology, Cho Ray Hospital
    4. university of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam
    5. radiology, Hôpital Necker
    6. Biostatistics, hôpital Saint Louis, Paris, France

    Published in Annals of Rheumatic DiseasesVolume 77, Issue Suppl 2

    DOI http://dx.doi.org/10.1136/annrheumdis-2018-eular.5027

    Citation

    Bardin T, Tran K, Nguyen Q, et al
    OP0357 Hyperechoic deposits in the renal medulla are associated with severe gout and decreased egfr: a transversal study in 503 vietnamese patients
    Annals of the Rheumatic Diseases 2018;77:224.

    Publication history

    First published June 12, 2018.

    Copyright information

    © 2016, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

    Background Renal medulla crystal deposits have been demonstrated by pathology in severe gout but little studied by ultrasound (US) scan.

    Objectives To assess the frequency of hyperechoic renal medulla (HERM) in gouty patients and factors associated with their development.

    Methods Renal US scan using a Ecube 9 echograph (Alpinion S. Korea), was performed in gout patients (ACR/EULAR criteria) consecutively seen at the Vien Gut general clinic, Ho Chi Minh City, Vietnam, and receiving no ULT at presentation. Age and sex of patients, gout features, associated diseases, serum (S) uric acid (UA), eGFR (MDRD), urinary lab stick parameters, urine UA/creatinine ratio, and fractional clearance of urate (FCU) were recorded. Patients with HERM were counted and compared with those who had no medullary deposits by the Wilcoxon rank sum test for continuous varables and the Fischer exact test for categorical variables. Multivariable logistic model was used to assess relation between variables at inclusion in the study and presence of medulla deposits.

    Results 503 consecutive patients (500 males) were included. They had a median age of 46 years, median BMI of 25 kg/m2, median gout duration of 4 years. 280 (56%) had clinical tophi, 154 (31%) urate arthropathy, 28;56%) urolithiasis, 112 (22%) hypertension, 58 (11.5%) type 2 diabetes, 5 (1%) coronary heart disease. Their median eGFR was 78 ml/min, SUA 423 micromol/L, FCU 0.063, urine UA/creatinine ratio 0.253, urinary pH 6.

    Diffuse and bilateral HERM on the B mode with frequent twinkling artefacts on the Doppler mode was identified in 181 (36%) of the 503 patients. Univariate analysis showed that HERM associated with higher age, longer duration of gout, clinical tophi, urate arthropathy (p<0.0001 for each of the variables), higher uricemia (p=0.001), hypertension (p=0.0008), CHD (p=0.0006), lower eGFR (p<0.0001), leucocyturia (p=0.02), proteinuria (p=0.02). No association with US-diagnosed urolithiasis, hematuria, urine UA/creatinine ratio, FCU and urinary pH was found. In multivariate analysis, log of the duration of gout (0R: 2.22 (CI: 1.63–3.08), p<0.001), clinical tophi (OR: 8.21 (4.23–16.91) p<0.001), urate arthropathy (OR: 3.74 (2.18–6.52, p<0.001), and lower eGFR (OR: 0.86 (0.75–0.99) for each 10 ml/min decrease, p=0.04) were significantly associated with HERM.

    Conclusions In our gout population, HERM was observed in 36% of patients,correlated with decreased renal function, and clearly associated with severe gout, but not with features of uric acic lithiasis.

    Disclosure of Interest T. Bardin Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, K. M. Tran: None declared, Q. D. Nguyen: None declared, N. H. Le : None declared, P. Richette Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, P. Le Van: None declared, J.-M. Correas: None declared, M. Resche-Rigon: None declared

    Correlation between serum and synovial fluid estrogen concentrations: Comment on the article by Sowers et al

    Pascal Richette MD, PhD  Kathleen Laborde MD  Carole Boutron BS  Thomas Bardin MD Marie‐Thérèse Corvol MD, PhD  Jean‐François Savouret PhD

    Wiley Online Library, Volume 56, Issue 2, February 2007, Pages 698-698

    First published: 30 January 2007 

    https://doi.org/10.1002/art.22384

     

    To the Editor:

    There is already substantial evidence for a role of estrogen in cartilage homeostasis (1), and the recent interesting report by Sowers and colleagues (2) adds further support for the existence of a link between estrogen deprivation and osteoarthritis (OA). Sowers et al observed that low serum estradiol (E2) concentrations in women were associated with an increased risk of knee OA.

    Nevertheless, the mechanisms by which serum estrogen levels could influence cartilage homeostasis are still unclear. One of the important remaining questions is whether synovial fluid (SF) levels of estrogen parallel serum levels, because the potential effects of estrogen on avascular cartilage should be influenced mainly by local concentrations of the hormone.

    To answer this question, we evaluated the estrogen concentrations in paired SF and serum samples from 21 premenopausal or postmenopausal women with knee OA. SF was obtained from the knee during therapeutic arthrocentesis and was stored at −80°C until analyzed. Joint fluid samples were melted on ice and centrifuged at 10,000g for 15 minutes to remove cellular debris. Total E2 concentrations in SF and serum were determined by radioimmunoassay.

    The mean ± SD age of patients was 59 ± 11 years. E2 concentrations in serum and SF were above the detection limit (10 pg/ml) in 14 of 21 patients. In these patients, the mean ± SD serum and SF E2 concentrations were 38.25 ± 9.74 pg/ml and 18.83 ± 5.70 pg/ml, respectively. There was a high and positive correlation between serum and SF estrogen concentrations (r = 0.93, P < 0.0001). Age of patients was negatively correlated with serum (r = −0.79, P = 0.0003) and SF E2 levels (r = −0.62, P = 0.03).

    These results show that estradiol is present in human SF from OA joints, at concentrations closely reflecting serum levels. The increased incidence of OA in postmenopausal women might thus be explained by a decrease in local estrogen concentrations, because E2 has been shown to have antidegradative properties at physiologic levels (3-5).

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    • Present2010

      Endodontics Postdoctoral AEGD Program

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    Teaching History

    • 19971995

      Preclinical Endodnotics

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    • 20052003

      SELC 8160 Molar Endodontic Selective

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    • 20112010

      Endodontics Postdoctoral AEGD Program

      Lorem ipsum dolor sit amet, consectetur adipiscing elit. Sed ultrices ac elit sit amet porttitor. Suspendisse congue, erat vulputate pharetra mollis, est eros fermentum nibh, vitae rhoncus est arcu vitae elit.
    • 20112010

      Endodontics Postdoctoral AEGD Program

      Lorem ipsum dolor sit amet, consectetur adipiscing elit. Sed ultrices ac elit sit amet porttitor. Suspendisse congue, erat vulputate pharetra mollis, est eros fermentum nibh, vitae rhoncus est arcu vitae elit.
    • 20112010

      Endodontics Postdoctoral AEGD Program

      Lorem ipsum dolor sit amet, consectetur adipiscing elit. Sed ultrices ac elit sit amet porttitor. Suspendisse congue, erat vulputate pharetra mollis, est eros fermentum nibh, vitae rhoncus est arcu vitae elit.

    At My Office

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    I am at my office every day from 7:00 until 10:00 am, but you may consider a call to fix an appointment.

    At My Work

    You can find me at my Work located at Stanford University Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.

    I am at my office every day from 7:00 until 10:00 am, but you may consider a call to fix an appointment.

    At My Lab

    You can find me at my Work located at Stanford University Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.

    I am at my office every day from 7:00 until 10:00 am, but you may consider a call to fix an appointment.