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Gout: HELP
Articles by Dr. Fernando Perez-Ruiz
Based on 61 articles published since 2009
(Why 61 articles?)

Between 2009 and 2019, F. Perez-Ruiz wrote the following 61 articles about Gout.
+ Citations + Abstracts
Pages: 1 · 2 · 3
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 Guideline 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. 2012

Khanna, Dinesh / Khanna, Puja P / Fitzgerald, John D / Singh, Manjit K / Bae, Sangmee / Neogi, Tuhina / Pillinger, Michael H / Merill, Joan / Lee, Susan / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Perez-Ruiz, Fernando / Taylor, Will / Lioté, Frédéric / Choi, Hyon / Singh, Jasvinder A / Dalbeth, Nicola / Kaplan, Sanford / Niyyar, Vandana / Jones, Danielle / Yarows, Steven A / Roessler, Blake / Kerr, Gail / King, Charles / Levy, Gerald / Furst, Daniel E / Edwards, N Lawrence / Mandell, Brian / Schumacher, H Ralph / Robbins, Mark / Wenger, Neil / Terkeltaub, Robert / Anonymous2310738. ·University of Michigan, Ann Arbor, MI, USA. ·Arthritis Care Res (Hoboken) · Pubmed #23024029.

ABSTRACT: -- No abstract --

3 Guideline 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. 2012

Khanna, Dinesh / Fitzgerald, John D / Khanna, Puja P / Bae, Sangmee / Singh, Manjit K / Neogi, Tuhina / Pillinger, Michael H / Merill, Joan / Lee, Susan / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Perez-Ruiz, Fernando / Taylor, Will / Lioté, Frédéric / Choi, Hyon / Singh, Jasvinder A / Dalbeth, Nicola / Kaplan, Sanford / Niyyar, Vandana / Jones, Danielle / Yarows, Steven A / Roessler, Blake / Kerr, Gail / King, Charles / Levy, Gerald / Furst, Daniel E / Edwards, N Lawrence / Mandell, Brian / Schumacher, H Ralph / Robbins, Mark / Wenger, Neil / Terkeltaub, Robert / Anonymous2300738. ·University of Michigan, Ann Arbor, MI, USA. ·Arthritis Care Res (Hoboken) · Pubmed #23024028.

ABSTRACT: -- No abstract --

4 Editorial ACTH analogues medications for the treatment of crystal-induced acute inflammation. A target to be explored? 2013

Perez-Ruiz, Fernando / Herrero-Beites, Ana María. · ·Joint Bone Spine · Pubmed #23522803.

ABSTRACT: -- No abstract --

5 Editorial [Gout: past, present, and future]. 2011

Pérez Ruiz, Fernando. · ·Reumatol Clin · Pubmed #21794820.

ABSTRACT: -- No abstract --

6 Review Combination urate-lowering therapy in the treatment of gout: What is the evidence? 2019

Perez-Ruiz, Fernando / Dalbeth, Nicola. ·Rheumatology Division, Hospital Universitario Cruces, University of the Basque Country, Bilbao 48903, Spain. Electronic address: fperezruiz@telefonica.net. · Bone and Joint Research Group, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand. ·Semin Arthritis Rheum · Pubmed #30075988.

ABSTRACT: BACKGROUND: Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach. METHODS: Relevant published papers were identified by keyword search on PubMed and categorized according to the types of combination therapies included. Study methods and results were summarized. Outcomes of combination therapy were compared with respective monotherapies, where possible. RESULTS: Efficacy was assessed by changes in serum urate (sUA), urinary uric acid, gout flare rates, and /or tophi. Safety assessments, where reported, included adverse events and, for more recent studies, laboratory assessments. Early studies in the 1960s based on case reports or open-label designs and more recent, well-designed studies with large patient numbers provided consistent outcomes: that combination therapy with a uricosuric and a XOI provides substantially greater sUA lowering than achieved by either monotherapy. Greater sUA lowering translated to greater gout symptom control, including improved tophus resolution. CONCLUSIONS: Combination therapy with a uricosuric and an XOI offers additional sUA lowering compared to monotherapy alone and can provide benefit for achieving therapeutic targets in patients with gout who do not achieve target sUA or are intolerant of XOIs at appropriate monotherapy dosing.

7 Review International position paper on the appropriate use of uricosurics with the introduction of lesinurad. 2018

Jansen, Tim L / Perez-Ruiz, Fernando / Tausche, Anne-Kathrin / Richette, Pascal. ·Department of Rheumatology, VieCuri MC, Tegelseweg 210, 5912 BL, Venlo, The Netherlands. tjansen@viecuri.nl. · Medicine Department of Medicine and Nursery School, University of the Basque Country, Leioa, Spain. · Department of Rheumatology, University Clinic "Carl Gustav Carus" at the Technical University, Fetscherstrasse 74, D-01309, Dresden, Germany. · Service de Rhumatologie, Inserm, UMR1132, Hôpital Lariboisière, F-75010, Paris, France. · Université Paris Diderot, Sorbonne Paris Cité, F-75205, Paris, France. ·Clin Rheumatol · Pubmed #30244431.

ABSTRACT: Over the last 70 years, pharmacotherapy in gout with urate-lowering drugs has consisted of four drugs only: In 1952, a mild uricosuric probenecid became available, the xanthine oxidase inhibitor Allopurinol in 1964, and the latter became the most frequently used urate-lowering drug worldwide; in the Eurozone, the uricosuric benzbromarone was welcomed in 1977. Only in 2002, the potent non-purine xanthine oxidase inhibitor febuxostat was introduced. In many countries, uricosurics such as probenecid and benzbromarone have not been available up to now, and these days, the new uricosuric lesinurad is the first uricosuric that may be introduced in these countries, which is the reason for describing the position this novel uricosuric deserves in treating gout. Recent literature will be shortly reviewed, and the current proposed position for lesinurad will be given as an aid for clinicians.

8 Review Treat to target in gout. 2018

Perez-Ruiz, Fernando / Moreno-Lledó, Aitana / Urionagüena, Irati / Dickson, Alastair J. ·Rheumatology Division, Hospital Universitario Cruces, Biocruces Health Research Institute, and University of the Basque Country. · Family physician, Las Arenas Healthcare Centre, Biscay, Spain. · Primary Care Rheumatology Society & Honorary Associate, Centre of Health Economics, University of York, UK. ·Rheumatology (Oxford) · Pubmed #29272512.

ABSTRACT: The treat-to-target (T2T) approach has been successfully implemented in a number of diseases. T2T has been proposed for rheumatic diseases such as RA, spondyloarthritis, lupus, and recently for gout. The level of evidence for such approaches differs from one condition to the other (moderate to high for hyperlipidaemia, for example). Practice is based on the best available evidence at any time, and in absence of good evidence for T2T in gout, some suggest a conservative only-treat-symptoms approach. Evidence suggests that not treating gout to target in the long term is overall associated with worsening outcomes, such as flares, tophi and structural damage, which is associated to loss of quality of life and mortality. Different targets have been proposed for hyperuricaemia in gout; lower than 6 mg/dl (0.36 mmol/l) for all patients, at least <5 mg/dl (0.30 mmol/l) for patients with severe-polyarticular or tophaceous-gout.

9 Review Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal studies. 2017

Nielsen, Sabrina M / Bartels, Else M / Henriksen, Marius / Wæhrens, Eva E / Gudbergsen, Henrik / Bliddal, Henning / Astrup, Arne / Knop, Filip K / Carmona, Loreto / Taylor, William J / Singh, Jasvinder A / Perez-Ruiz, Fernando / Kristensen, Lars E / Christensen, Robin. ·The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. · Department of Physical and Occupational Therapy, Bispebjerg and Frederiksberg, Copenhagen, Denmark. · The Research Initiative for Activity Studies and Occupational Therapy, General Practice, Department of Public Health, University of Southern Denmark, Odense, Denmark. · Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark. · Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. · Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Institutode Salud Musculoesquelética, Madrid, Spain. · Department of Medicine, University of Otago, Wellington, New Zealand. · Department of Medicine, University of Alabama at Birmingham, & Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA. · Rheumatology Division, Hospital de Cruces, Baracaldo, Spain. ·Ann Rheum Dis · Pubmed #28866649.

ABSTRACT: OBJECTIVES: Weight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout. METHODS: We searched six databases for longitudinal studies, reporting the effect of weight loss in overweight/obese gout patients. Risk of bias was assessed using the tool Risk of Bias in Non-Randomised Studies of Interventions. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. RESULTS: From 3991 potentially eligible studies, 10 were included (including one randomised trial). Interventions included diet with/without physical activity, bariatric surgery, diuretics, metformin or no intervention. Mean weight losses ranged from 3 kg to 34 kg. Clinical heterogeneity in study characteristics precluded meta-analysis. The effect on serum uric acid (sUA) ranged from -168 to 30 μmol/L, and 0%-60% patients achieving sUA target (<360 μmol/L). Six out of eight studies (75%) showed beneficial effects on gout attacks. Two studies indicated dose-response relationship for sUA, achieving sUA target and gout attacks. At short term, temporary increased sUA and gout attacks tended to occur after bariatric surgery. CONCLUSIONS: The available evidence is in favour of weight loss for overweight/obese gout patients, with low, moderate and low quality of evidence for effects on sUA, achieving sUA target and gout attacks, respectively. At short term, unfavourable effects may occur. Since the current evidence consists of a few studies (mostly observational) of low methodological quality, there is an urgent need to initiate rigorous prospective studies (preferably randomised controlled trials). SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016037937.

10 Review Imaging of gout: New tools and biomarkers? 2016

Araujo, Elizabeth G / Manger, Bernhard / Perez-Ruiz, Fernando / Thiele, Ralf G. ·Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. · Rheumatology Division, Hospital de Cruces, Baracaldo, Vizcaya, Spain. · Department of Medicine, Allergy/Immunology & Rheumatology Division, University of Rochester, School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: Ralf_Thiele@URMC.Rochester.edu. ·Best Pract Res Clin Rheumatol · Pubmed #27931959.

ABSTRACT: While joint aspiration and crystal identification by polarizing microscopy remain the gold standard for diagnosing tophaceous gout, agreement among medical and ancillary health personnel examining synovial fluid using polarizing microscopy for the detection of monosodium urate (MSU) crystals appears to be poor. Imaging modalities, including conventional radiography (CR), ultrasonography (US), magnetic resonance imaging (MRI), and dual-energy computed tomography (DECT), have been found to provide information on the deposition of MSU crystals in tissues, and the consequences of such deposition. CR can demonstrate typical "punched out lesions" with marginal overhangs, but the sensitivity for erosion detection is better for DECT and US. US is inexpensive and can identify tophus deposition in and around joints, erosions, and tissue inflammation if power Doppler US is used. MRI can show tophi, bone marrow edema, and inflammation, but MRI findings of tophi may be nonspecific. DECT can identify and color-code tophaceous material, and provide an overview of the tophus burden of a joint area. Because of the lower number of available studies, the strength of evidence for the newer imaging can be improved through further research.

11 Review Urate lowering therapies in the treatment of gout: a systematic review and meta-analysis. 2016

Borghi, C / Perez-Ruiz, F. ·University of Bologna, Bologna, Italy. Claudio.borghi@unibo.it. ·Eur Rev Med Pharmacol Sci · Pubmed #27010159.

ABSTRACT: OBJECTIVE: In patients with gout, serum uric acid (sUA) concentrations should be lowered at least below the target of 6 mg/dL (even below 5 mg/dL in patients with severe gout). To achieve this goal, urate lowering medications (ULMs) should be considered. Currently-used ULMs include xanthine-oxidase inhibitors such as allopurinol, febuxostat, as well as available uricosuric agents. However, evidence comparing these agents remains scant. We have conducted a systematic review and meta-analysis to retrieve evidence on the clinical trials on the above-mentioned drugs in the treatment of gout. MATERIALS AND METHODS: The following efficacy outcomes were considered in the meta-analysis: (1) % of patients meeting the therapeutic target for sUA level (<6 mg/dl) and (2) percentage reduction in sUA concentration at the end of the study compared with baseline values. An explorative analysis on safety was also conducted. RESULTS: In total, 16 papers concerned febuxostat, 15 allopurinol, 4 benzbromarone and none involved probenecid. Overall, 70.7% of patients reached the target of sUA with febuxostat therapy; the reduction in sUA was 45.3%. Corresponding figures with allopurinol were 44.4% and 33.8%, respectively. The number of patients on benzbromarone (N=129) was too low to retrieve definitive findings. The advantage for febuxostat over allopurinol was evident also in patients with renal dysfunction. Safety analysis favored febuxostat over allopurinol (OR 0.85; 95% CI: 0.75-0.97). CONCLUSIONS: On the basis of the reported data, febuxostat can play a major role in the treatment of hyperuricaemia and gout. Febuxostat is a suitable pharmacological option for first line treatment of gout, given its established efficacy and safety, documented in a high number of clinical studies and in daily practice.

12 Review Febuxostat for the chronic management of hyperuricemia in patients with gout. 2016

Chinchilla, Sandra Pamela / Urionaguena, Irati / Perez-Ruiz, Fernando. ·a Rheumatology Division , Hospital Universitario Cruces, OSI EE-Cruces , Baracaldo , Spain. · b Biocruces Health Research Institute , Baracaldo , Spain. ·Expert Rev Clin Pharmacol · Pubmed #26942273.

ABSTRACT: Febuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR), and a major alternative to the scarce number of urate-lowering medications available in the last decades. Its inhibition of XOR is more potent than allopurinol in a mg to mg comparison, what is associated to achievement of serum urate target more frequently than allopurinol at doses tested in clinical trials, especially in patients with the highest baseline serum urate levels. Its pharmacokinetics is not greatly dependent on renal clearance, contrary to allopurinol, what may be an advantage in patients with chronic kidney disease. Several trials are further evaluating both the cardiovascular safety of febuxostat and its possible beneficial effect on renal function preservation. Still scarce, but clinically interesting, evidence on its use in transplant patients has been recently released.

13 Review Epidemiology and health-related services. 2016

Perez-Ruiz, Fernando / Urionagüena, Irati / Carmona-Ortells, Loreto. ·aRheumatology Division, Biocruces Health Research Institute bRheumatology Division, Hospital Universitario Cruces, OSI EE-Cruces, Baracaldo cInstituto de Salud Musculoesquelética, Madrid, Spain. ·Curr Opin Rheumatol · Pubmed #26807788.

ABSTRACT: PURPOSE OF REVIEW: This article presents recent epidemiologic contributions focusing on gout-related conditions, especially if controversial, to find plausible, despite hypothetical, mechanistic explanations from the clinician perspective. RECENT FINDINGS: The prevalence of gout is increasing, but it is only partially clear that the incidence may be increasing as well. Direct associations of gout with increased risk of diabetes, black races, neurodegenerative disorders, and sugar-enriched foods have been recently questioned. A negative association with smoking has been reported, and new evidence shows that the impact of diet may be independent of obesity. Kidney disease and diuretics have been confirmed to be associated with gout, whereas new data on aging and menopause have come to challenge apparently established disease mechanisms. Regarding treatments, increase in bladder cancer associated with chronic allopurinol use has been reported, and the positive effect of urate-lowering treatment on cardiovascular events has been contested. SUMMARY: Epidemiological data in gout-related conditions are still evolving and claim for future cohort or intervention studies to prove causality. Controversies in epidemiological results fertilize the ground for studies to prove mechanisms and causality and provides a unique opportunity for clinical intervention to improve outcomes, especially with regard to treatments.

14 Review Inflammation: a possible mechanism for a causative role of hyperuricemia/gout in cardiovascular disease. 2015

Perez-Ruiz, F / Becker, M A. ·a a Servicio de Reumatología, Hospital Universitario Cruces, Instituto de Investigación Biomédica BioCruces , Vizcaya , Spain. · b b Department of Medicine , The University of Chicago Pritzker School of Medicine , Chicago , Illinois , USA. ·Curr Med Res Opin · Pubmed #26414731.

ABSTRACT: Hyperuricemia and gout are independent risk factors associated with the development of hypertension, metabolic syndrome, vascular damage, and renal disease. Whether these risk factors are causally related to these important chronic co-morbidities remains uncertain, but inflammation may provide a mechanistic explanation. Hyperuricemia and gout negatively affect vascular function by exerting pro-oxidant effects and by decreasing nitric oxide bioavailability, thus inducing inflammation and endothelial dysfunction, which may promote hypertension, metabolic syndrome, and cardiovascular (CV) disease. This paper presents and discusses current understanding of the diverse influences promoting hyperuricemia and gout and the basis of acute and chronic hyperuricemia/gout-related inflammation. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.

15 Review Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group. 2015

Grainger, Rebecca / Dalbeth, Nicola / Keen, Helen / Durcan, Laura / Lawrence Edwards, N / Perez-Ruiz, Fernando / Diaz-Torne, Cesar / Singh, Jasvinder A / Khanna, Dinesh / Simon, Lee S / Taylor, William J. ·From the Department of Medicine, University of Otago Wellington, Wellington; Department of Medicine, University of Auckland, New Zealand; Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Medicine, University of Florida, Gainesville, Florida, USA; Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya; Division of Rheumatology, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama; Division of Rheumatology, Department of Medicine, University of Michigan, Ann Arbor, Michigan; SDG LLC, Cambridge, Massachusetts, USA.R. Grainger, PhD, FRACP, Senior Lecturer, Rheumatologist, Department of Medicine, University of Otago Wellington; N. Dalbeth, MD, FRACP, Associate Professor, Department of Medicine, University of Auckland; L. Durcan, Rheumatology Fellow, MD, Mater Misericordiae University Hospital; H. Keen, PhD, Associate Professor, School of Medicine and Pharmacology, University of Western Australia; N.L. Edwards, MD, Professor of Medicine, Department of Medicine, University of Florida; F. Perez-Ruiz, MD, Professor, Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute; C. Diaz-Torne, PhD, Associate Professor and Rheumatologist; J.A. Singh, MBBS, MPH, Associate Professor of Medicine; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham; D. Khanna, MD, MSc, Associate Professor of Medicine, Division of Rheumatology, Department of Medicine, University of Michigan; L.S. Simon, MD, Principal Advisor, SDG LLC; W.J. Taylor, PhD, FRACP, Associate Professor and Rheumatologist, Department of Medicine, University of Otago Wellington. ·J Rheumatol · Pubmed #25641895.

ABSTRACT: OBJECTIVE: The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0. METHODS: During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented. RESULTS: The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage. CONCLUSION: The working group prioritized gaps in the data and identified a research agenda.

16 Review New medications in development for the treatment of hyperuricemia of gout. 2015

Diaz-Torné, Cesar / Perez-Herrero, Nuria / Perez-Ruiz, Fernando. ·aDivision of Rheumatology, Hospital Santa Creu i San Pau, Barcelona bBiomedical Sciences School, Universidad Rey Juan Carlos, Madrid cDivision of Rheumatology, Hospital Universitario Cruces, and BioCruces Health Research Institute, Vizcaya, Spain. ·Curr Opin Rheumatol · Pubmed #25603039.

ABSTRACT: PURPOSE OF REVIEW: To update recent developments in medications targeting hyperuricemia, but not including medications recently labelled in the European Union and the United States. RECENT FINDINGS: A new xanthine oxidase inhibitor, Topiloric (Fujiyakuhin Co., Ltd. Japan) Uriadec (Sanwa Kagaku Kenkyusho Co., Ltd. Japan), has been developed and labelled in Japan. An inhibitor of purine nucleoside phosphorylase, Ulodesine, is in development in combination with allopurinol. The rest of the medications in the pipeline for hyperuricemia are targeting renal transporters of uric acid, mainly URAT1 and OAT4, acting as uricosuric agents. Most of them, such as lesinurad and arhalofenate, are being tested in trials in combination with allopurinol and febuxostat. The most potent RDEA3170 is being tested in monotherapy, but also associated with febuxostat. Recently, medications showing dual activity, inhibiting both xanthine oxidoreductase and URAT1, have been communicated or started exploratory clinical trials. There is no report of medications targeting other transporters such as Glut9 or ABCG2. SUMMARY: There are a number of medications in the pipeline targeting hyperuricemia, mostly uricosurics in combination with xanthine oxidase inhibitors, but some targeting both xanthine oxidoreductase and URAT1. Increasing the number of available medications will ensure proper control of hyperuricemia to target serum urate levels in the near future for most, if not all, patients with hyperuricemia.

17 Review A review of uric acid, crystal deposition disease, and gout. 2015

Perez-Ruiz, Fernando / Dalbeth, Nicola / Bardin, Tomas. ·Servicio de Reumatologia, Hospital Universitario Cruces, and BioCruces Health Research Institute, 48903, Baracaldo, Vizcaya, Spain, fernando.perezruiz@osakidetza.net. ·Adv Ther · Pubmed #25533440.

ABSTRACT: There has been increased interest in gout in both academic and clinical practice settings. Several reasons may explain this. The prevalence of both hyperuricemia and gout has risen in the last decades in developed countries and therefore the burden of gout has increased. The association of hyperuricemia and gout with cardiovascular outcomes and the opportunity of further benefits of intervention on hyperuricemia have been recently highlighted in the literature. Imaging techniques have proven to be useful for detection of urate deposition, even prior to the first clinical symptoms, enabling the evaluation of the extent of deposition and providing objective measurement of crystal depletion during urate-lowering treatment. Treating to target is increasingly used as the approach to treatment of diverse diseases. Therefore, different targets have been recommended for different stages of the burden of disease and for different stages of treatment. The final strategic target, to which any effort should be taken into consideration, is to completely dissolve urate crystals in tissues and therefore avoid further symptoms and structural damage of involved musculoskeletal structures. In summary, evidence suggest that an early approach to the treatment of gout and associated comorbidities is advisable, that new imaging techniques may help to evaluate both the burden of deposition and response to urate-lowering treatment in selected patients, and finally that the final strategic objective of healthcare for patients with gout is to completely resolve urate crystal deposits.

18 Review Safety of allopurinol compared with other urate-lowering drugs in patients with gout: a systematic review and meta-analysis. 2015

Castrejon, Isabel / Toledano, Esther / Rosario, María Piedad / Loza, Estíbaliz / Pérez-Ruiz, Fernando / Carmona, Loreto. ·Division of Rheumatology, Rush University Medical Center, 1611 West Harrison Street, Suite 510, Chicago, IL, 60612, USA, isabelcastrejonf@gmail.com. ·Rheumatol Int · Pubmed #25519877.

ABSTRACT: SELECTION CRITERIA: (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis. PRIMARY OUTCOMES: rate of adverse events and death. The quality was assessed with the Jadad's scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40-240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6-85) and febuxostat (range 41.8-80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.

19 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.

20 Review Clinical manifestations and diagnosis of gout. 2014

Perez-Ruiz, Fernando / Castillo, Edwin / Chinchilla, Sandra P / Herrero-Beites, Ana M. ·Division of Rheumatology, BioCruces Health Institute, Hospital Universitario Cruces, Pza Cruces sn, Baracaldo 48903, Spain. Electronic address: fernando.perezruiz@osakidetza.net. · Division of Rheumatology, Hospital Universitario Cruces, Pza Cruces sn, Baracaldo 48903, Spain. · Division of Physical Medicine, Hospital de Górliz, Astondo Ibiltoki, km. 2, Górliz 48630, Spain. ·Rheum Dis Clin North Am · Pubmed #24703343.

ABSTRACT: Gout has been academically considered to be a step-up disease consisting of different stages: acute gout, intercritical gout, and chronic gout. This simple approach may lead to misinterpretation and misdiagnosis. In clinical practice, we should consider gout as a single disease with either or both acute (most commonly, episodes of acute inflammation) and persistent clinical manifestations, but not restricted to chronic synovitis. In this article, an innovative, practical, and rational approach to the clinical manifestations and diagnosis of gout is presented, which may be supportive for clinicians involved in everyday care and management of patients with gout.

21 Review Canakinumab for gout: a specific, patient-profiled indication. 2014

Perez-Ruiz, Fernando / Chinchilla, Sandra P / Herrero-Beites, Ana María. ·Rheumatology Division, Hospital Universitario Cruces, Vizcaya, Spain. ·Expert Rev Clin Immunol · Pubmed #24451032.

ABSTRACT: The role of interleukin-1 (IL-1) in inflammation induced by crystals, and especially by monosodium urate crystals (MSUCs), has raised much interest in both basic and clinical investigation. Several drugs have been developed, and more are still in development, to block IL-1 driven inflammation, though to date only canakinumab (blocking IL-1β) has been labelled, yet limited to the European Union, with a restricted indication to treat episodes of acute inflammation (EAIs) in patients with gout in whom other therapeutic choices are unacceptable. Other medications developed for IL-1 blocking, such as anakinra and rilonacept, have been tested in gout patients in clinical trials, but lack label approval and may be further restricted to orphan indication in gout. Notwithstanding, the use of IL-1 blockade to prevent EAIs in gout looks promising, but no drug has yet obtained approval for such an indication.

22 Review Evaluation and treatment of gout as a chronic disease. 2012

Perez-Ruiz, Fernando / Herrero-Beites, Ana Maria. ·Rheumatology Division, Hospital Universitario Cruces, Pza Cruces, Baracaldo, Vizcaya, Spain. fperezruiz@telefonica.net ·Adv Ther · Pubmed #23104464.

ABSTRACT: Gout is a disease caused by deposition of monosodium urate crystals in tissues. One of the limitations for successful treatment of gout is to consider it as an intermittent disease rather than a chronic inflammatory disease which, if improperly treated, leads to chronic clinical manifestations. In addition, gout is linked to increased cardiovascular morbidity and mortality.Urate-lowering therapy comprises both nonpharmacologic and pharmacologic interventions, but most patients will need urate-lowering drugs to achieve target therapeutic serum urate levels. Reaching target serum urate levels is associated with improvement in clinical outcomes, including a reduction of acute inflammation episodes, resolution of tophi, and improvement in health-related quality of life perception.A number of urate-lowering drugs are available but a number of patients fail to achieve or maintain therapeutic serum urate levels and go on to develop refractory chronic gout. For such patients, efforts have been made to develop new treatments (e.g., febuxostat or pegloticase).This review intends to increase the awareness of gout as a chronic deposition disease, and show that efforts should be made to properly control serum urate levels in order to achieve complete disappearance of urate crystal deposition.

23 Review Gout: why is this curable disease so seldom cured? 2012

Doherty, Michael / Jansen, Tim L / Nuki, George / Pascual, Eliseo / Perez-Ruiz, Fernando / Punzi, Leonardo / So, Alexander K / Bardin, Thomas. ·Department of Rheumatology, City Hospital, Nottingham, UK. Michael.Doherty@nottingham.ac.uk ·Ann Rheum Dis · Pubmed #22863577.

ABSTRACT: Gout is the most common inflammatory arthritis and one in which pathogenesis and risk factors are best understood. One of the treatment objectives in current guidelines is 'cure'. However, audits show that only a minority of patients with gout receive adequate advice and treatment. Suboptimal care and outcomes reflect inappropriately negative perceptions of the disease, both in patients and providers. Historically, gout has been portrayed as a benign and even comical condition that is self-inflicted through overeating and alcohol excess. Doctors often focus on managing acute attacks rather than viewing gout as a chronic progressive crystal deposition disease. Urate-lowering treatment is underprescribed and often underdosed. Appropriate education of patients and doctors, catalysed by recent introduction of new urate-lowering treatments after many years with no drug development in the field, may help to overcome these barriers and improve management of this easily diagnosed and curable form of potentially severe arthritis.

24 Review Methods of tophus assessment in clinical trials of chronic gout: a systematic literature review and pictorial reference guide. 2011

Dalbeth, Nicola / Schauer, Cameron / Macdonald, Patricia / Perez-Ruiz, Fernando / Schumacher, H Ralph / Hamburger, Steve / Choi, Hyon K / McQueen, Fiona M / Doyle, Anthony / Taylor, William J. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz ·Ann Rheum Dis · Pubmed #21216814.

ABSTRACT: OBJECTIVE: To identify methods of tophus measurement for gout studies, summarise the properties of these methods and compile a detailed pictorial reference guide to demonstrate the methods. METHODS: A systematic search strategy for methods of tophus measurement was formulated. For each method, papers were assessed by two reviewers to summarise information according to the specific components of the Outcomes Measures in Rheumatology (OMERACT) filter: feasibility, truth and discrimination. Detailed images were obtained to construct the reference guide. RESULTS: Eight methods of tophus measurement were identified: counting the total number of tophi, physical measurement using tape measure, physical measurement using Vernier callipers, digital photography, ultrasonography (US), MRI, CT and dual energy CT. Feasibility aspects of the methods are well documented. Physical measurement techniques are more feasible than advanced imaging methods, but do not allow for assessment of intra-articular tophi or for data storage and central reading. The truth aspect of the filter has been documented for many methods, particularly Vernier callipers, US, MRI and CT. Reliability of most methods has been reported as very good or excellent. Sensitivity to change has been reported for all methods except MRI and CT. CONCLUSION: A variety of methods of tophus assessment have been described for use in clinical trials of chronic gout. Physical measurement techniques (particularly the Vernier calliper method) and US measurement of tophus size appear to meet most aspects of the OMERACT filter.

25 Review Epidemiology of gout: an update. 2010

Smith, E U R / Díaz-Torné, C / Perez-Ruiz, F / March, L M. ·Department of Rheumatology, Northern Clinical School, University of Sydney, Building 35, Block 4, Level 4, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. emma.smith@sydney.edu.au ·Best Pract Res Clin Rheumatol · Pubmed #21665128.

ABSTRACT: Gout is the most common inflammatory joint disease in men, characterised by formation of monosodium urate (MSU) crystals in the synovial fluid of joints and in other tissues. The epidemiology of gout provides us with the understanding of the disease distribution and its determinants. In an attempt to update the knowledge on the topic, more recent research reports on the descriptive epidemiology of gout are reviewed in this article. The review describes clinical characteristics and case definitions of gout, including the Rome and New York diagnosis criteria of gout, '1977 American Rheumatism Association (ARA) criteria' and the 10 key propositions of the European League Against Rheumatism (EULAR) recommendations. Gout incidence, prevalence, morbidity and mortality, geographical variation of the disease, relevant risk factors for both the occurrence and outcome of gout and trends of the disease over time are then described. Difficulties in obtaining the information and data reported are also discussed.