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Gout: HELP
Articles by Pascal Richette
Based on 45 articles published since 2008
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Between 2008 and 2019, P. Richette wrote the following 45 articles about Gout.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline 2016 updated EULAR evidence-based recommendations for the management of gout. 2017

Richette, P / Doherty, M / Pascual, E / Barskova, V / Becce, F / Castañeda-Sanabria, J / Coyfish, M / Guillo, S / Jansen, T L / Janssens, H / Lioté, F / Mallen, C / Nuki, G / Perez-Ruiz, F / Pimentao, J / Punzi, L / Pywell, T / So, A / Tausche, A K / Uhlig, T / Zavada, J / Zhang, W / Tubach, F / Bardin, T. ·AP-HP, hôpital Lariboisière, service de Rhumatologie, F-75010 Paris, France; Inserm, UMR1132, Hôpital Lariboisière, F-75010 Paris, France; Universitè Paris Diderot, Sorbonne Paris Citè, F-75205 Paris, France. · Academic Rheumatology, University of Nottingham, Nottingham, UK. · Department of Rheumatology, Hospital General Universitario de Alicante, Alicante, Spain. · Institute of Rheumatology RAMS, Moscow, Russia. · Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland. · AP-HP, Dèpartement d'Epidèmiologie et Recherche Clinique, Hôpital Bichat, Paris, France: APHP, Centre de Pharmacoèpidèmiologie, Paris, France: Univ Paris Diderot, Paris, France: INSERM UMR 1123 ECEVE, Paris, France. · Patient from Nottingham, UK, Paris. · Department of Rheumatology, VieCuri Medical Centre, Venlo, and Scientific IQ HealthCare, Radboud UMC, Nijmegen, The Netherlands. · Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, Netherlands. · Arthritis Research UK Primary Care Centre University of Keele, Keele, UK. · Osteoarticular Research Group, University of Edinburgh, Edinburgh, UK. · Seccion de Rheumatologia, Hospital de Cruces, Baracaldo, Spain. · Rheumatology Unit, Clínica Coração de Jesus, Lisbon, Portugal. · Rheumatology Unit, University of Padova, Padova, Italy. · Service de Rhumatologie, CHUV and Universitè de Lausanne, Lausanne, Switzerland. · Department of Rheumatology, University Clinic at the Technical University Dresden, Germany. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Czech Republic. ·Ann Rheum Dis · Pubmed #27457514.

ABSTRACT: BACKGROUND: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. METHODS: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. RESULTS: Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. CONCLUSIONS: These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.

2 Editorial Treatment of gout: where are we now? 2018

Richette, Pascal. ·Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Rhumatologie. · INSERM UMR-1132, Hôpital Lariboisière, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. ·Rheumatology (Oxford) · Pubmed #29272509.

ABSTRACT: -- No abstract --

3 Editorial Purine-rich foods: an innocent bystander of gout attacks? 2012

Richette, Pascal / Bardin, Thomas. · ·Ann Rheum Dis · Pubmed #22805973.

ABSTRACT: -- No abstract --

4 Editorial Debulking the urate load to feel better. 2012

Richette, Pascal. · ·J Rheumatol · Pubmed #22753797.

ABSTRACT: -- No abstract --

5 Review Investigational drugs for hyperuricemia, an update on recent developments. 2018

Pascart, Tristan / Richette, Pascal. ·a Department of Rheumatology , Lille Catholic Hospitals, University of Lille , Lomme , France. · b EA 4490, PMOI, Physiopathologie des Maladies Osseuses Inflammatoires , University of Lille , Lille , France. · c Department of Rheumatology , Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisiere , Paris , France. · d Department of Rheumatology , INSERM U1132 and University Paris-Diderot , Paris , France. ·Expert Opin Investig Drugs · Pubmed #29718730.

ABSTRACT: INTRODUCTION: The significant proportion of gout patients not reaching serum urate levels below 6.0 mg/dL and the debated pathogenicity of hyperuricemia (HU) itself motivate investigators to develop new drugs to decrease uricemia. AREAS COVERED: This review discusses the drugs considered to be in active development from pre-clinical to phase III studies. This review covers 11 drugs in development, including a xanthine oxidase inhibitor (topiroxostat), uricosurics (verinurad, arhalofenate, UR-1102, tranilast), dual inhibitors (RLBN1001, KUX-1151), a uricase (pergsiticase), an inhibitor of hypoxanthine production (ulodesine), and drugs with yet-to-explain mechanisms of action (levotofisopam, tuna extracts). EXPERT OPINION: Drugs well advanced in their development - particularly arhalofenate, verinurad and topiroxostat - open the prospect of patient-comorbidity-tailored HU management. Development of novel therapies provides new insight into our understanding of gout and HU, particularly potential pathogenicity. Apart from potency to decrease serum urate levels and good tolerance profiles, novel therapies will need to focus on administration modalities facilitating treatment adherence.

6 Review Role of dual-energy CT in the diagnosis and follow-up of gout: systematic analysis of the literature. 2018

Ramon, André / Bohm-Sigrand, Amélie / Pottecher, Pierre / Richette, Pascal / Maillefert, Jean-Francis / Devilliers, Herve / Ornetti, Paul. ·Department of Rheumatology, Dijon University Hospital, 14 rue Gaffarel, 21000, Dijon, France. · Department of Radiology, Section of Musculoskeletal Imaging and Intervention, Dijon University Hospital, Dijon, France. · LE2I UMR CNRS 6306, Arts et Métiers, University of Burgundy, Dijon, France. · INSERM U1132 and University Paris-Diderot, Paris, France. · Department of Rheumatology, Hopital Lariboisiere, Paris, France. · INSERM UMR1093-CAPS, Bourgogne Franche-Comté University, Dijon, France. · Department of Internal Medicine, Dijon University Hospital, Dijon, France. · CIC INSERM 1432, Centre Hospitalier Universitaire de Dijon, F-21000, Dijon, France. · Department of Rheumatology, Dijon University Hospital, 14 rue Gaffarel, 21000, Dijon, France. paul.ornetti@chu-dijon.fr. · INSERM UMR1093-CAPS, Bourgogne Franche-Comté University, Dijon, France. paul.ornetti@chu-dijon.fr. ·Clin Rheumatol · Pubmed #29350330.

ABSTRACT: The aim of this systematic review was to determine the potential role of dual-energy CT in the diagnosis and follow-up of gout with regard to the Outcome Measures in Rheumatology (OMERACT) filter. A systematic analysis of the literature was conducted using the MEDLINE and Cochrane databases and published abstracts of international congresses, according to the criteria of the OMERACT filter: feasibility, reproducibility, validity versus laboratory (serum urate, MSU synovial fluid aspirate) and other imaging modalities for gout, and its sensitivity to change in patients on urate lowering therapy (ULT). Thirty-two articles were found representing a total of 1502 patients. The data on feasibility showed that the examination took little time and involved low levels of radiation but had current limited availability. Intra- and inter-observer reproducibility was excellent, with intra-class correlation coefficients > 0.9. Validity in comparison with polarized-light microscopy showed good sensitivity and specificity (> 80%). The diagnostic performance was better than that of radiography and conventional CT-scan and at least equivalent to that of ultrasonography. The sensitivity to change varied with effect sizes from 0.05 (low) to 1.24 (high) for decrease in the tophus volume following different ULT in gout patients. Dual-energy CT-scan is a reproducible and accurate imaging modality for the diagnosis of gout, particularly for tophaceous gout (intra- or extra-articular). It can become a second-line imaging modality of choice in cases of diagnostic doubt, such as ultrasonography. Its role remains uncertain in the follow-up of gout patients treated with ULT and needs further clarification.

7 Review Novel uricosurics. 2018

Bardin, Thomas / Richette, Pascal. ·Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Rhumatologie. · INSERM UMR-1132, Hôpital Lariboisière, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. ·Rheumatology (Oxford) · Pubmed #29272511.

ABSTRACT: Objective: According to recent guidelines, the mainstay of urate-lowering therapies remains xanthine oxidase inhibition. However, some patients with gout show failure to achieve the predefined target of 5-6 mg/dl with xanthine oxidase inhibitors alone, so alternative drugs are needed. The aim of this study was to review studies of novel drugs targeting uric acid transporter 1 (URAT1) and/or other urate transporters for the management of gout. Methods: MeSH terms were used to identify phase 2/3 trials assessing the efficacy of novel uricosurics. A narrative review of novel drugs targeting URAT1 and/or other urate transporters for the management of gout is provided. Results: Lesinurad is a recently approved uricosuric that inhibits URAT1 and the organic ion transporter organic anion transporter 4 (OAT4). Phase 3 trials showed that lesinurad, combined with allopurinol or febuxostat, is a potent urate-lowering therapeutic with an acceptable safety profile. Arhalofenate, another emerging uricosuric, also interacts with URAT1 and organic anion transporter 4. Phase 2 trials suggested that it can both lower serum UA levels and reduce the risk of flares. Conclusions: New drugs inhibiting URAT1 should cover the unmet need for patients with failure to respond or with contraindications to xanthine oxidase inhibitors.

8 Review Cardiac and renal protective effects of urate-lowering therapy. 2018

Richette, Pascal / Latourte, Augustin / Bardin, Thomas. ·Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie. · INSERM UMR-1132, Hôpital Lariboisière and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. ·Rheumatology (Oxford) · Pubmed #29272510.

ABSTRACT: Patients with gout often have co-morbidities such as cardiovascular disease, renal failure and metabolic syndrome components. Some studies, but not all, have suggested that hyperuricaemia and gout are associated with increased risk of myocardial infarction, renal failure and death primarily because of increased risk of cardiovascular events. Therefore, knowledge of the effects of urate-lowering therapy (ULT) on co-morbidities, in particular cardiovascular events and chronic kidney disease, is crucial. Randomized controlled trials (RCTs) have suggested that allopurinol, a xanthine oxidase inhibitor, could improve exercise capacity in patients with chronic stable angina and could decrease blood pressure in adolescents. In contrast, a well-designed RCT found no effect of allopurinol in patients with heart failure. The impact of ULT in patients with chronic kidney disease is unclear. Some RCTs found that allopurinol could slow the decline in kidney function, whereas a recent controlled trial found no benefit of febuxostat. Large randomized placebo-controlled trials are warranted to confirm or not the benefit of ULT on co-morbidities.

9 Review Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN). 2017

Dalbeth, Nicola / Bardin, Thomas / Doherty, Michael / Lioté, Frédéric / Richette, Pascal / Saag, Kenneth G / So, Alexander K / Stamp, Lisa K / Choi, Hyon K / Terkeltaub, Robert. ·Department of Medicine, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand. · University Paris Diderot Cité Sorbonne, Service de Rhumatologie, Centre Viggo Petersen, Lariboisière Hospital, INSERM U1132, Paris, France. · Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham (UAB), 820 Faculty Office Tower, 510 20th Street, Birmingham, Alabama 35294-3408, USA. · Service of Rheumatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland. · Department of Medicine, University of Otago, Christchurch, P.O. BOX 4345, Christchurch 8140, New Zealand. · Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit Street, Harvard Medical School, Boston, Massachusetts 02114, USA. · VA San Diego Healthcare System, 111K, 3350 La Jolla Village Drive, San Diego, California 92161, USA. ·Nat Rev Rheumatol · Pubmed #28794514.

ABSTRACT: In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them. The G-CAN position, presented here, is that the fundamental pathophysiological knowledge underlying gout care, and evidence from clinical experience and clinical trials, supports a treat-to-target approach for gout aimed at lowering serum urate levels to below the saturation threshold at which monosodium urate crystals form. This practice, which is truly evidence-based and promotes the steady reduction in tissue urate crystal deposits, is promoted by the ACR, EULAR and 3e Initiative recommendations. By contrast, the ACP does not provide a clear recommendation for urate-lowering therapy (ULT) for patients with frequent, recurrent flares or those with tophi, nor does it recommend monitoring serum urate levels of patients prescribed ULT. Results from emerging clinical trials that have gout symptoms as the primary end point are expected to resolve this debate for all clinicians in the near term future.

10 Review Current and future therapies for gout. 2017

Pascart, Tristan / Richette, Pascal. ·a Department of Rheumatology, Lille Catholic Hospitals , University of Lille , Lomme , France. · b EA 4490, PMOI, Physiopathologie des Maladies Osseuses Inflammatoires , University of Lille , Lille , France. · c Department of Rheumatology, Assistance Publique-Hôpitaux de Paris , Hôpital Lariboisiere , Paris , France. · d INSERM U1132 and University Paris-Diderot , Paris , France. ·Expert Opin Pharmacother · Pubmed #28689430.

ABSTRACT: INTRODUCTION: Gout is a common disease responsible for recurrent flares triggered by the deposition of monosodium urate crystals secondary to longstanding hyperuricaemia. The management of gout implies both the treatment of flares and the treatment of hyperuricaemia itself. Recent improvement in the understanding of the disease led to the development of new drugs. Areas covered: This review covers data related to 'old' treatments of flares and hyperuricaemia, evidence on the recently approved drugs and emerging therapies in development. Expert opinion: Recent data provide a good grasp of the optimal use of colchicine, corticosteroids and NSAIDs for the treatment of flares. Interleukin-1 blocking therapies have an increasing role in the management of difficult-to-treat gout. Sub-optimal use of allopurinol is common and its potency to reduce serum uric acid (SUA) levels is underestimated. Febuxostat effectively reduces SUA levels. New uricosurics, notably lesinurad and arhalofenate, in combination with xanthine oxidase inhibitors, offer promising perspectives to help a greater number of patients achieve sufficient SUA reduction.

11 Review Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options. 2017

Bardin, Thomas / Richette, Pascal. ·Université Paris Diderot, UFR médicale, Paris, France. thomas.bardin@aphp.fr. · Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Rhumatologie, Paris, Cedex, France. thomas.bardin@aphp.fr. · INSERM 1132, Université Paris-Diderot, Hôpital Lariboisière, Paris, France. thomas.bardin@aphp.fr. · French-Vietnamese Research Center on Gout, Ho Chi Minh City, Vietnam. thomas.bardin@aphp.fr. · Université Paris Diderot, UFR médicale, Paris, France. · Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Rhumatologie, Paris, Cedex, France. · INSERM 1132, Université Paris-Diderot, Hôpital Lariboisière, Paris, France. ·BMC Med · Pubmed #28669352.

ABSTRACT: Gout, the most prevalent inflammatory arthritis worldwide, is associated with cardiovascular and renal diseases, and is an independent predictor of premature death. The frequencies of obesity, chronic kidney disease (CKD), hypertension, type 2 diabetes, dyslipidaemias, cardiac diseases (including coronary heart disease, heart failure and atrial fibrillation), stroke and peripheral arterial disease have been repeatedly shown to be increased in gout. Therefore, the screening and care of these comorbidities as well as of cardiovascular risk factors are of outmost importance in patients with gout. Comorbidities, especially CKD, and drugs prescribed for their treatment, also impact gout management. Numerous epidemiological studies have shown the association of asymptomatic hyperuricaemia with the above-mentioned diseases and cardiovascular risk factors. Animal studies have also produced a mechanistic approach to the vascular toxicity of soluble urate. However, causality remains uncertain because confounders, reverse causality or common etiological factors might explain the epidemiological results. Additionally, these uncertainties remain unsolved despite recent studies using Mendelian randomisation or therapeutic approaches. Thus, large randomised placebo-controlled trials are still needed to assess the benefits of treating asymptomatic hyperuricaemia.

12 Review Current management of gout: practical messages from 2016 EULAR guidelines. 2017

Nuki, George / Doherty, Michael / Richette, Pascal. · ·Pol Arch Intern Med · Pubmed #28430170.

ABSTRACT: The European League Against Rheumatism published updated recommendations for the management of gout in 2016, comprising 3 overarching principles and 11 key recommendations for clinical practice. Patient education about the pathophysiology of gout and its comorbidities, as well as the existence of effective treatments are important, and understanding the principles of managing acute attacks and eliminating urate crystals by lifelong lowering of the serum urate (SU) below a target level are essential. Advice about lifestyle, diet, weight, and other risk factors, as well as the need to screen for, and manage, comorbidities is emphasized. For the treatment of flares, colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and oral or intraarticular steroids, or a combination thereof, are recommended. In patients with frequent flares and contraindications to colchicine, NSAIDs, and corticosteroids, an interleukin-1 blocker should be considered. Urate-lowering therapy (ULT) should be discussed from the first presentation of the disease, and SU levels should be maintained at less than 6 mg/dl (360 µmol/l), or less than 5 mg/dl (300 µmol/l) in patients with severe gout. Allopurinol is recommended as first-line ULT with dose adjustment according to renal function. If the SU target cannot be achieved with allopurinol, then febuxostat, a uricosuric, or combining a xanthine oxidase inhibitor with a uricosuric should be considered. All ULTs should be started at low dose and titrated upwards until the SU target is achieved. Unless contraindicated, flare prophylaxis with low-dose colchicine or with NSAIDs at low dosage is recommended during the first 6 months of ULT. In patients with refractory gout, pegloticase can be considered.

13 Review The management of hyperuricemia with urate deposition. 2015

Desideri, G / Puig, J G / Richette, P. ·a a Department of Life , Health and Environmental Sciences, University of L'Aquila , L'Aquila , Italy. · b b Division of Internal Medicine , Hospital Universitario La Paz, Universidad Autónoma de Madrid , Spain. · c c Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris , Paris , France. · d d Hôpital Lariboisière, Fédération de Rhumatologie , Paris , France. ·Curr Med Res Opin · Pubmed #26414734.

ABSTRACT: Recent epidemiological data suggest a progressive increase of serum levels of uric acid worldwide. This rise in the prevalence of hyperuricemia may be related to the epidemic diffusion of overweight and obesity as well as the shifts in diet with increased consumption of foods rich in purines, alcoholic consumption, and soft drinks sweetened with fructose. The rise in serum uric acid levels worldwide may be regarded as leading an increased risk for gout and other systemic diseases, especially in the cardio-renal system. Therefore, careful management of hyperuricemia with urate deposition is crucial to prevent or even treat those systemic diseases. Despite this, hyperuricemia and gout often remain untreated. This paper reviews current evidence on the management of hyperuricemia with urate deposition, with a focus on its most controversial aspects. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.

14 Review Impact of anti-inflammatory therapies, xanthine oxidase inhibitors and other urate-lowering therapies on cardiovascular diseases in gout. 2015

Richette, Pascal / Frazier, Aline / Bardin, Thomas. ·aUniversité Paris Diderot, Sorbonne Paris Cité, UFR de Médecine bAP-HP, Service de Rhumatologie, Pôle appareil Locomoteur, Hôpital Lariboisière, Paris, France. ·Curr Opin Rheumatol · Pubmed #25594854.

ABSTRACT: PURPOSE OF REVIEW: The purpose of this study is to give an overview of recently published articles covering the impact of anti-inflammatory therapies, xanthine oxidase inhibitors and other urate-lowering therapies on cardiovascular diseases in gout. RECENT FINDINGS: In patients with gout, long-term xanthine oxidase inhibition might reduce some cardiovascular comorbidities because of the dual effect of lowering serum uric acid levels and reducing free-radical production during uric acid formation. Among the anti-inflammatory therapies, colchicine has been shown to reduce some major cardiovascular events. SUMMARY: Epidemiological and experimental studies have shown that hyperuricaemia and gout are independent risk factors for cardiovascular diseases. The mechanisms that link high serum uric acid levels and gout with cardiovascular diseases are multifactorial, implicating low-grade systemic inflammation and xanthine oxidase activity as well as the deleterious effect of hyperuricaemia itself.

15 Review Improving cardiovascular and renal outcomes in gout: what should we target? 2014

Richette, Pascal / Perez-Ruiz, Fernando / Doherty, Michael / Jansen, Tim L / Nuki, George / Pascual, Eliseo / Punzi, Leonardo / So, Alexander K / Bardin, Thomas. ·Hôpital Lariboisière, Fédération de Rhumatologie, Centre Viggo Petersen 2, rue Ambroise Parè 75475 Cedex 10, Paris, France. · Servicio de Reumatología and BioCruces Health Research Institute, Cruces University Hospital, Plaza Cruces S/N, 48903 Barakaldo, Spain. · Division of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital Nottingham, Hucknall Road, Nottingham NG5 1PB, UK. · Department of Rheumatology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, Netherlands. · Department of Rheumatology, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK. · Department of Medicine, Rheumatology Section, Alicante University and General Hospital, University Miguel Hernández, Av. Pintor Baeza 12, Alicante 03010, Spain. · Department of Rheumatology, Rheumatology Unit, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. · Service of Rheumatology, Centre Hospitalier Universitaire Vaudois, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland. ·Nat Rev Rheumatol · Pubmed #25136785.

ABSTRACT: Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.

16 Review Pharmacokinetics considerations for gout treatments. 2014

Richette, Pascal / Frazier, Aline / Bardin, Thomas. ·Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine , F-75205 Paris , France. ·Expert Opin Drug Metab Toxicol · Pubmed #24809930.

ABSTRACT: INTRODUCTION: Patients with gout often have comorbid conditions such as renal failure, cardiovascular disease and metabolic syndrome. The presence and required treatment of these conditions can make the treatment of gout challenging. Knowledge of the pharmacokinetics of the available drugs for the management of gout is mandatory. AREAS COVERED: A MEDLINE PubMed search for articles published in English from January 1990 to January 2014 was completed using the terms: pharmacokinetics, colchicine, canakinumab, allopurinol, febuxostat, pegloticase, gout, toxicity, drug interaction. EXPERT OPINION: Colchicine is a drug with a narrow therapeutic-toxicity window. Co-prescription with strong CYP3A4 or P-glycoprotein inhibitors can greatly modify its pharmacokinetics and is to be avoided. Elimination of canakinumab mainly occurs via intracellular catabolism, following receptor mediator endocytosis. Canakinumab appears to be a good alternative for patients with contraindications to colchicine, NSAIDs and corticosteroids. For patients with renal impairment, some authors recommend that the allopurinol maximum dosage should be adjusted to creatinine clearance. If the urate target cannot be achieved, the therapy should be switched to febuxostat, which is appropriate with mild-to-moderate renal failure. Anti-pegloticase antibodies affect the pharmacokinetics of the drug because they increase its clearance, with loss of pegloticase activity.

17 Review Prophylaxis for acute gout flares after initiation of urate-lowering therapy. 2014

Latourte, Augustin / Bardin, Thomas / Richette, Pascal. ·Université Paris 7, UFR Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie and INSERM 1132, Hôpital Lariboisière, Paris, France. Université Paris 7, UFR Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie and INSERM 1132, Hôpital Lariboisière, Paris, France. · Université Paris 7, UFR Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie and INSERM 1132, Hôpital Lariboisière, Paris, France. · Université Paris 7, UFR Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie and INSERM 1132, Hôpital Lariboisière, Paris, France. Université Paris 7, UFR Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie and INSERM 1132, Hôpital Lariboisière, Paris, France. pascal.richette@lrb.aphp.fr. ·Rheumatology (Oxford) · Pubmed #24758886.

ABSTRACT: This review summarizes evidence relating to prophylaxis for gout flares after the initiation of urate-lowering therapy (ULT). We searched MEDLINE via PubMed for articles published in English from 1963 to 2013 using MEsH terms covering all aspects of prophylaxis for flares. Dispersion of monosodium urate crystals during the initial phase of deposit dissolution with ULT exposes the patient to an increased rate of acute flares that could contribute to poor treatment adherence. Slow titration of ULT might decrease the risk of flares. According to the most recent international recommendation, the two first-line options for prophylaxis are low-dose colchicine (0.5 mg once or twice a day) or low-dose NSAIDs such as naproxen 250 mg orally twice a day. They can be given for up to 6 months. If these drugs are contraindicated, not tolerated or ineffective, low-dose corticosteroids (prednisone or prednisolone) might be used. Recently, reports for four trials described the efficacy of canakinumab and rilonacept, two IL-1 inhibitors, for preventing flares during the initiation of allopurinol therapy. Prophylaxis for flares induced by ULT is an important consideration in gout management. Low-dose colchicine and low-dose NSAIDs are the recommended first-line therapies. Although no IL-1 blockers are approved as prophylactic treatment, this class of drug could become an interesting option for patients with gout with intolerance or contraindication to colchicine, NSAIDs or corticosteroids.

18 Review Definition of hyperuricemia and gouty conditions. 2014

Bardin, Thomas / Richette, Pascal. ·Department of Rheumatology, Lariboisière Hospital, Assistance Publique Hôpitaux de Paris, University Paris VII, Paris, France. ·Curr Opin Rheumatol · Pubmed #24419750.

ABSTRACT: PURPOSE OF THE REVIEW: To define gout conditions and hyperuricemia. RECENT FINDINGS: Gout is defined as an arthritic condition resulting from the deposition of monosodium urate (MSU) crystals in and/or around joints, following long-standing hyperuricemia. Several recent ultrasound studies disclosed MSU deposits in a large proportion of asymptomatic hyperuricemic patients. A gout condition defined by asymptomatic MSU deposits can therefore be individualized. Such asymptomatic deposits appear to precede the occurrence of flares, which seem to be triggered by mobilization of preformed crystals. Hyperuricemia appears to be the main, if not the only, risk factor for gout. Recent studies also support the view that hyperuricemia is an independent risk factor for renal and cardiovascular diseases. The level at which uricemia becomes abnormal is still disputed. This lack of consensus precludes comparison of studies using different definitions and impairs the understanding of gout by doctors and patients. We propose to define hyperuricemia as greater than 6 mg/dl, as the life-long risk of gout seems to start at this level. This definition is identical to the minimum uricemia target of urate-lowering drugs (ULDs). SUMMARY: Asymptomatic MSU crystals deposits can now be identified and precede the onset of gout flares. Defining hyperuricemia as greater than 6 mg/dl would have the advantage to give the same value for normal and ULD-targeted uricemia, which would facilitate patients' adherence to this target.

19 Review Novel drug discovery strategies for gout. 2013

Richette, Pascal / Garay, Ricardo. ·Université Paris 7, UFR Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, 75475 Paris Cedex 10, France. pascal.richette@lrb.aphp.fr ·Expert Opin Drug Discov · Pubmed #23231400.

ABSTRACT: INTRODUCTION: The increasing prevalence of gout has been accompanied by a growing number of patients intolerant to or with disease refractory to available urate-lowering therapies. These difficult-to-treat patients currently represent about 3 - 5% of people with gout in Europe and the United States, which highlights the need for emerging treatments to effectively lower urate levels. AREAS COVERED: In this review, the authors describe the putative pharmacological targets to lower urate levels. Furthermore, the authors discuss various strategies used to discover novel molecules or to improve available drugs used to treat gout. EXPERT OPINION: Major advances in our understanding of urate renal transport from in vitro, animal and genetic studies could lead to the development of novel uricosuric drugs. Targeting one or several urate transporters such as urate transporter 1, organic anion transporter 4 and 10 and glucose transporter 9 is promising. Moreover, design of small molecules capable of blocking the site activity of enzymes other than xanthine oxidase and involved in the purine pathway could generate novel hypouricemic drugs. Finally, polyethylene glycol (PEGylation) can significantly extend the biological half-life of drugs and reduce antigenicity and immunogenicity of proteins. The technology has been successfully applied to an uricase (pegloticase), but the drug was immunogenic in some patients. Strategies to decrease the immunogenicity of a PEG-uricase are important for developing next-generation uricase.

20 Review [Gout: an overview of available urate lowering therapies]. 2012

Richette, P. ·Fédération de rhumatologie, université Paris-Diderot, Sorbonne Paris Cité, hôpital Lariboisière, Assistance publique-Hôpitaux de Paris, Paris, France. pascal.richette@lrb.aphp.fr ·Ann Pharm Fr · Pubmed #22655581.

ABSTRACT: The aim of urate-lowering therapy is to maintain urate concentration below the saturation point for monosodium urate. This therapy dissolves crystal deposits and cures gout while it is maintained. EULAR guidelines recommend that plasma urate should be maintained at a concentration less than 360μM, and the British Guidelines less than 300μM. Urate-lowering therapy is indicated for patients with recurrent gout attacks, chronic arthropathy, tophi, and gout with uric acid stones. Allopurinol lowers uricemia through inhibition of xanthine oxidase activity. The maximum allowed dose is reduced in case of renal failure, which is relatively frequent in gouty patients. Febuxostat has been approved for the treatment of chronic hyperuricemia in conditions where urate deposition has already occurred. Febuxostat is a novel non-purine, selective inhibitor of xanthine oxidase, metabolized and excreted by the liver, so no dose adjustment appears to be necessary in patients with mild-to-moderate renal impairment. Another powerful hypo-uricemic drug is the PEG-uricase (pegloticase). Pegloticase is a uric acid-specific PEGylated recombinant mammalian uricase recently approved by the FDA for treatment of patients with refractory chronic gout.

21 Review Usefulness of ultrasonography for gout. 2012

Ottaviani, Sébastien / Bardin, Thomas / Richette, Pascal. ·UFR Médicale, Service De Rhumatologie, Université Paris-7, Hôpital Bichat, AP-HP, 46 rue Henri-Huchard, 75018 Paris, France. sebastien.ottaviani@bch.aphp.fr ·Joint Bone Spine · Pubmed #22386965.

ABSTRACT: Gout is a common arthritis caused by deposition of monosodium urate (MSU) crystals within joints secondary to chronic hyperuricemia. Joint damage can occur during evolution of the disease. The identification of MSU crystals in synovial fluid is the gold standard to diagnose gout. However, the diagnosis is sometimes difficult to do, particularly in atypical clinical presentations or when small joints are involved. Radiography is often normal at the early stage of gout. MRI and CT-scan are costly and availability of these imaging techniques may be problematic in clinical practice. Ultrasonography (US) appears useful for diagnosis and management of the disease. Several ultrasound features evocating gout have been described with different sensitivity and specificity. We reviewed the literature for evidence of the ability and usefulness of US for diagnosis of early-stage and established gout.

22 Review Therapeutic perspectives on uricases for gout. 2012

Garay, Ricardo P / El-Gewely, M Raafat / Labaune, Jean-Pierre / Richette, Pascal. ·Inserm U999, hôpital Marie-Lannelongue, université Paris-Sud, 92350 Le-Plessis-Robinson, France. ricardo.garay@orange.fr ·Joint Bone Spine · Pubmed #22366146.

ABSTRACT: Available recombinant uricases (rasburicase, pegloticase) are potent hypouricaemic agents for tophaceous gout, but their long-term use is in question. We have performed a literature review on uricases, using Scirus, PubMed, Science Direct, and several other search engines. We have also consulted the records of drug regulatory authorities and patents on uricases. Rasburicase (Fasturtec(®)) was approved in Europe for tumour lysis syndrome induced by chemotherapy, in a single daily infusion dose for a maximum of 7 days. A retrospective study (n=10) conducted in patients with gout and three clinical cases have shown that infusions spaced over time, over several months, ensure the control of serum uric acid and help to eliminate or significantly reduce the size of tophi. However, repeated gout attacks (despite colchicine) and hypersensitivity reactions (despite corticosteroids) have dampened enthusiasm for its use in gout. Pegloticase was recently approved by the Food and Drug Administration (FDA) for patients with chronic gout, refractory or intolerant to conventional hypouricaemic therapy. A 6 month study versus placebo showed that pegloticase (infused at 8 mg every 2 weeks), induced a significant decrease in plasma uric acid in about 40% of patients (associated with a tendency for tophi dissolution). However, the remaining patients were non-responders, which correlated with the formation of pegloticase antibodies and infusion reactions. Research efforts are needed to develop less immunogenic uricases. In conclusion, some uricases could have an important role in the treatment of gout, for instance as a first-line treatment and over a short period of several months in patients with severe and tophaceous gout to allow rapid tophi dissolution.

23 Review [The epidemiology and genetic of gout]. 2011

Bardin, Thomas / Richette, Pascal. ·Université Paris 7, Assistance-publique-Hôpitaux de Paris, hôpital Lariboisière, UFR médicale, 2, rue Ambroise-Paré, 75475 Paris cedex 10, France. thomas.bardin@lrb.aphp.fr ·Presse Med · Pubmed #21752574.

ABSTRACT: Gout affects 1-2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in the prevalence of gout. Diet and genetic predisposition seem to be the main causal factors of primary gout. Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases. Genetic studies have found that variants of GLUT9 and ABCG2 were associated with urate levels.

24 Review [New therapeutic options for gout]. 2011

Richette, Pascal / Ottaviani, Sébastien / Bardin, Thomas. ·Université Paris 7, Assistance-publique-Hôpitaux de Paris, hôpital Lariboisière, fédération de rhumatologie, UFR médicale, 2, rue Ambroise-Paré, 75475 Paris Cedex 10, France. pascal.richette@lrb.aphp.fr ·Presse Med · Pubmed #21684104.

ABSTRACT: Chronic hyperuricemia and acute arthritis in severe gouty patients can be difficult to manage, in particular in patients with renal failure or with history of cardio vascular conditions. Hopefully, new drugs have been approved or will emerge, and will help to overcome these situations. Febuxostat has been recently approved in France for the treatment of chronic hyperuricemia in conditions where urate deposition has already occurred. Febuxostat is a novel non-purine, selective inhibitor of xanthine oxidase, metabolized and excreted by the liver, so no dose adjustment appears to be necessary in patients with mild-to-moderate renal impairment. Other novel hypouricemic drugs are the PEG-uricase (pegloticase), recently approved by the FDA, and a novel uricosuric drug (RDEA594), which is currently under development. The discovery that interleukin 1β (IL- β) plays a key role in the pathogenesis of acute attacks of gout has prompted to assess the efficacy of IL-1 β blockers in patients with acute gout. Biologic agents that inhibit IL-1 β such as canakinumab, rilonacept and anakinra have shown promising results for the treatment of gouty arthritis.

25 Review Colchicine for the treatment of gout. 2010

Richette, Pascal / Bardin, Thomas. ·Fédération de Rhumatologie, Hôpital Lariboisière, Paris, France. pascal.richette@lrb.aphp.fr ·Expert Opin Pharmacother · Pubmed #21050036.

ABSTRACT: IMPORTANCE OF THE FIELD: Colchicine, used for a long period in gout, was approved for the first time in 2009 by the FDA for the prophylaxis and the treatment of acute attack, on the basis of a pivotal trial that showed the efficacy in the very short term - that is 24 h of a well-tolerated, low-dose regimen of Colcrys (colchicine, URL Pharma, Philadelphia, USA) to reduce pain in patients with acute gout - when given early. AREAS COVERED IN THIS REVIEW: We searched the Cochrane Library and Medline for articles published in English from January 2000 to August 2010 using the following search terms: colchicine, gout, efficacy, toxicity, drug interaction. Some information from the FDA was also included because it provides comprehensive overviews that are within the scope of this review. WHAT THE READER WILL GAIN: Colchicine is a drug with a narrow therapeutic-toxicity window and with an important variability in tolerance between subjects. This paper reviews recent important findings on its pharmacology and efficacy which will allow a better use of this drug for the treatment of acute attack of gout. Also, pharmacokinetic, drug interaction and toxicity of colchicine are discussed. TAKE HOME MESSAGE: Low-dose colchicine (1.8 mg over 1 h) taken as early as possible ('pills in the pocket') is effective in reducing pain and is well tolerated in patients with acute gout.

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