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Gout: HELP
Articles from Duke University
Based on 41 articles published since 2010
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These are the 41 published articles about Gout that originated from Duke University during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. 2013

Hershfield, M S / Callaghan, J T / Tassaneeyakul, W / Mushiroda, T / Thorn, C F / Klein, T E / Lee, M T M. ·Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. ·Clin Pharmacol Ther · Pubmed #23232549.

ABSTRACT: Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A variant allele of the human leukocyte antigen (HLA)-B, HLA-B*58:01, associates strongly with allopurinolinduced SCAR. We have summarized the evidence from the published literature and developed peer-reviewed guidelines for allopurinol use based on HLA-B genotype.

2 Editorial Is It Time for Gout Flare Treatment to Move into the 21st Century? 2019

Keenan, Robert T. ·Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. Robert.keenan@duke.edu. ·J Rheumatol · Pubmed #31262752.

ABSTRACT: -- No abstract --

3 Editorial Editorial Commentary: Prevention and treatment of atrial fibrillation: Is hyperuricemia the next target? 2019

Black-Maier, Eric / Daubert, James P. ·Duke Center for Atrial Fibrillation, Electrophysiology Section, Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. · Duke Center for Atrial Fibrillation, Electrophysiology Section, Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. Electronic address: james.daubert@duke.edu. ·Trends Cardiovasc Med · Pubmed #30057151.

ABSTRACT: -- No abstract --

4 Review Moving the Needle: Improving the Care of the Gout Patient. 2019

Golenbiewski, Jon / Keenan, Robert T. ·Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. · Duke Gout and Crystal Arthropathies Clinic, Durham, NC, USA. robert.keenan@duke.edu. · Duke Specialty Infusion Centers, Durham, NC, USA. robert.keenan@duke.edu. · Division of Rheumatology and Immunology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. robert.keenan@duke.edu. ·Rheumatol Ther · Pubmed #30826988.

ABSTRACT: Gout is a the most common inflammatory arthritis in the United States. It is a significant cause of morbidity, disability, lost work days, and high healthcare utilization due to intermittent attacks, chronic inflammation, and joint damage. Despite our understanding of the prelude and pathophysiology of gout, hyperuricemia, it is still poorly misunderstood by patients and poorly managed by healthcare providers. Several parallel treatment paradigms have been developed by professional societies around the world based on the understanding of how hyperuricemia occurs, gout epidemiology, expert opinion, and clinical trials data in order to lower uric acid and eventually eliminate the patient's crystal burden. This review focuses on both the treatment of acute attacks, and more importantly, the long-term management of gout and the lowering of serum uric acid levels to a goal of < 6 mg/dl (0.360 mmol/l) or treating to target. Treating to a target serum uric acid goal is an opportunity to decrease morbidity and improve the quality of care of every gout patient.

5 Review Joint Clinical Consensus Statement of the American College of Foot and Ankle Surgeons® and the American Association of Nurse Practitioners®: Etiology, Diagnosis, and Treatment Consensus for Gouty Arthritis of the Foot and Ankle. 2018

Mirmiran, Roya / Bush, Tom / Cerra, Michele M / Grambart, Sean / Kauschinger, Elaine / Younger, Melissa / Zychowicz, Michael. ·Foot and Ankle Surgeon, Department of Surgery, Sutter Medical Group, Sacramento, CA. Electronic address: Roya.Mirmiran@aol.com. · Associate Professor and Assistant Dean for Practice, University of North Carolina at Chapel Hill Schools of Nursing and Medicine, Chapel Hill, NC. · Director of the Duke NP/PA Rheumatology Fellowship Program & Faculty, Department of Medicine, Duke University School of Medicine, NC. · Foot and Ankle Surgeon, Carle Physician Group, Department of Surgery, Champaign, IL. · Clinical Assistant Professor, Duke University School of Nursing, Durham, NC. · Podiatric Research Fellow, Penn Presbyterian Medical Center, Philadelphia, PA. · Professor and Director of MSN Program & Lead Faculty in Orthopedic NP Specialty, Duke University School of Nursing, Durham, NC. ·J Foot Ankle Surg · Pubmed #30368431.

ABSTRACT: Gout is a condition that commonly affects the foot and ankle, and practitioners who treat these structures should be aware of the methods to diagnose and treat this form of arthritis. Practitioners also need to recognize extra-articular manifestations of the disease. Although the acutely red, hot, swollen joint is a common presentation, chronic tophaceous gout can be associated with pain, nodule formation, and cutaneous compromise. Since the underlying causes that lead to excessive monosodium urate deposition may be treatable, early and accurate diagnosis can be very beneficial and may even prevent articular degeneration.

6 Review Limitations of the Current Standards of Care for Treating Gout and Crystal Deposition in the Primary Care Setting: A Review. 2017

Keenan, Robert T. ·Department of Medicine, Division of Rheumatology and Immunology, Duke University School of Medicine, Durham, North Carolina. Electronic address: robert.keenan@duke.edu. ·Clin Ther · Pubmed #28089200.

ABSTRACT: PURPOSE: This article outlines several important issues regarding the management of patients with gout. The topics discussed include best practices for gout based on the most current guidelines, opportunities for improving gout management, and current and emerging therapies for gout. METHODS: [PubMed and Google Scholar databases] were search for all articles and trials published before 2016, using the key terms [hyperuricemia, gout, tophi, joint erosion, joint damage, treatment guidelines, American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), flare, comorbidity, epidemiology, adherence, serum uric acid (sUA), monosodium urate (MSU), <6 mg/dL, MSU crystal formation, as well as individual drug names and classes of treatments of interest (allopurinol, febuxostat, colchicine, non-steroidal anti-inflammatories (NSAIDs)]. Studies were selected that presented data on gout treatment, including drugs under development, and on the management of gout from both the physician and patient perspectives. The reference lists of identified articles were searched manually for additional publications. FINDINGS: Gout, a progressive debilitating form of inflammatory arthritis, is caused by factors that elevate serum uric acid (sUA) levels, leading to hyperuricemia. Continued elevated sUA can result in monosodium urate crystal deposition in joints and soft tissues, causing acute and chronic inflammation. Crystal deposition can lead to chronic gout, with an increased number of flares, tophi development, and structural joint damage. The aims of gout treatment are to reduce the sUA level to <6 mg/dL, to inhibit the formation of new crystals, and to promote the dissolution of existing crystals. Gout is often poorly managed for several reasons, including a lack of adherence to treatment guidelines by health care providers, patients' poor adherence to therapy, and differences between a provider's and patient's perspectives regarding treatment. IMPLICATIONS: Patients need to be educated about their diagnosis and management of the disease, such as the importance of compliance with long-term treatment. Gout treatment may also confounded by contraindications to current standards of therapy and the limitations of current treatment paradigms. Recently approved medications, as well as drugs under development, may provide new ways for reaching the sUA target and also "curing" the disease.

7 Review New and Pipeline Drugs for Gout. 2016

Keenan, Robert T / Schlesinger, Naomi. ·Department of Medicine, Duke University School of Medicine, Durham, NC, USA. robert.keenan@duke.edu. · Division of Rheumatology, Duke University Medical Center, 200 Trent Drive DUMC 3544, Durham, NC, USA. robert.keenan@duke.edu. · Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. ·Curr Rheumatol Rep · Pubmed #27097819.

ABSTRACT: Gout is the most common inflammatory arthropathy in the western world. Affecting millions and accounting for lost wages, increased health care costs, and significant disability, it remains a burden for those afflicted, their families, and the health care system. Despite the availability of a number of effective therapies, gout is often inadequately treated, and its impact on the patients overall health and well-being is underestimated by physicians and patients alike. For many decades, controlling acute flares was the priority in the management of gout. More recently, however, a deeper understanding of gout pathophysiology has resulted in a new appreciation that gout impacts the patient with consequences well beyond the episodes of acute inflammatory arthritis. Reflecting the chronic nature of the disease, gout treatment needs to be chronic as well, and aimed at reducing the underlying cause of gout-hyperuricemia-as well as the symptom of acute attacks. Therapy therefore requires both urate lowering and anti-inflammatory strategies. Unfortunately, the most commonly used urate lowering and anti-inflammatory treatments may be problematic in some gout patients, who often have multiple comorbidities that establish relative contraindications. Novel urate lowering therapies, and new medications to treat and prevent acute gouty flares, can not only improve care of the individual; they can also lead to a better discourse for the edification of those who manage and are managed for this underestimated disease. In this paper, we discuss new and pipeline drugs for acute gout, prophylactic anti-inflammatory therapies as well as urate lowering therapies.

8 Review The effect of angiotensin II receptor blockers on hyperuricemia. 2015

Wolff, Marissa L / Cruz, Jennifer L / Vanderman, Adam J / Brown, Jamie N. ·Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, 508 Fulton Street (182), Durham, NC 27705, USA. · Geriatric Research Education and Clinical Center, Durham VA Medical Center, Durham, NC, USA. · Pharmacy Service, Durham VA Medical Center, Durham, NC, USA. ·Ther Adv Chronic Dis · Pubmed #26568810.

ABSTRACT: The objective of this review was to explore the efficacy of angiotensin II receptor blockers (ARBs) for the treatment of hyperuricemia in individuals diagnosed with gout or hyperuricemia defined as ⩾7 mg/dl at baseline. A literature search of MEDLINE (1946 to June 2015) and EMBASE (1947 to June 2015) was conducted. The following search terms were used: 'uric acid', 'urate transporter', 'gout', 'angiotensin II receptor blockers', 'hyperuricemia' and the names for individual ARBs, as well as any combinations of these terms. Studies were excluded that did not explore fractional excretion or serum uric acid as an endpoint, if patients did not have a diagnosis of gout or hyperuricemia at baseline, or if they were non-English language. A total of eight studies met the inclusion criteria. Of the eight studies identified, six explored ARB monotherapy and two studies investigated ARBs as adjunct therapy. Losartan demonstrated statistically significant reductions in serum uric acid levels or increases in fractional excretion of uric acid in all studies, whereas no other ARB reached statistical benefit. The effect of ARBs on the occurrence of gout attacks or other clinical outcomes were not represented. Four studies evaluated safety effects of these agents indicating abnormalities such as minor changes in lab values. In conclusion, losartan is the only ARB that has consistently demonstrated a significant reduction in serum uric acid levels, although the significance of impacting clinical outcomes remains unknown. Losartan appears to be a safe and efficacious agent to lower serum uric acid levels in patients with hyperuricemia.

9 Review Colchicine--Update on mechanisms of action and therapeutic uses. 2015

Leung, Ying Ying / Yao Hui, Laura Li / Kraus, Virginia B. ·Department of Rheumatology & Immunology, Singapore General Hospital, The Academia, Level 4, 20 College Rd, Singapore 169856; Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore. Electronic address: katyccc@hotmail.com. · Department of Rheumatology & Immunology, Singapore General Hospital, The Academia, Level 4, 20 College Rd, Singapore 169856. · Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC. ·Semin Arthritis Rheum · Pubmed #26228647.

ABSTRACT: OBJECTIVES: To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. METHODS: We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. RESULTS: The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. CONCLUSION: Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions.

10 Review Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy. 2014

Baraf, Herbert S B / Yood, Robert A / Ottery, Faith D / Sundy, John S / Becker, Michael A. ·From the *Center for Rheumatology & Bone Research, Wheaton, MD; †Reliant Medical Group, Worcester, MA; ‡Savient Pharmaceuticals, Inc, Bridgewater, NJ; §Duke University Medical Center, Durham, NC; and ║The University of Chicago, Chicago, IL. ·J Clin Rheumatol · Pubmed #25417679.

ABSTRACT: BACKGROUND: In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported. OBJECTIVE: The objective of this study was to provide a detailed account of IRs with pegloticase therapy. METHODS: Data from 2 replicate, 6-month randomized trials and an open-label extension study were pooled. Infusions of pegloticase (8 mg) were administered biweekly or monthly; all patients received prophylaxis (antihistamine, acetaminophen, and corticosteroid) and were tested for urate levels prior to each infusion. An IR was defined by protocol as any otherwise unexplained adverse event or cluster of temporally related events occurring during or within 2 hours of infusion. RESULTS: Infusion-related reactions occurred in 94 (45%) of 208 patients receiving pegloticase; 10 patients reported IRs at first infusion and 84 during subsequent infusions. Chest discomfort (15%), flushing (12%), and dyspnea (11%) were the most common symptoms. Most IRs were rated mild or moderate; 7% were rated severe. All IRs resolved with slowing, interrupting, or stopping the infusion. No patient required blood pressure or ventilatory support. Infusion-related reactions were associated with loss of pegloticase urate-lowering efficacy: 91% of all IRs occurred in patients with preinfusion serum uric acid concentrations (sUA) greater than 6 mg/dL. For patients sustaining preinfusion sUA of less than 6 mg/dL, IRs occurred in fewer than 1 per 100 infusions. CONCLUSIONS: Phase 3 trial data combined with post hoc analyses demonstrated that knowledge of sUA preceding each pegloticase infusion and cessation of therapy when urate-lowering efficacy is lost provide a means to optimize the safety of pegloticase in clinical practice.

11 Review Saturnine gout, redux: a review. 2013

Dalvi, Sam R / Pillinger, Michael H. ·Department of Medicine, Division of Rheumatology, NYU Hospital for Joint Diseases, New York, NY, USA. Samir.Dalvi@duke.edu ·Am J Med · Pubmed #23510947.

ABSTRACT: Illicitly distilled beverages (colloquially referred to as moonshine) account for approximately one third of alcohol consumption worldwide. Moonshine is often produced in makeshift distilling units composed of old, repurposed parts, whose component elements can leach into the distillate. Consequently, the resultant beverages may inadvertently contain harmful toxins, one of which is the metal lead. One manifestation of chronic lead toxicity-from moonshine or other forms of chronic lead poisoning-is the rheumatologic entity known as saturnine gout. With the increasing prevalence of gout over the past few decades, physicians should be aware of the association of moonshine consumption or lead toxicity with gouty arthritis. In this article, we present an overview of saturnine gout, beginning with a discussion of lead poisoning in antiquity and tracing its path to modern times. The contribution of lead to human disease and the clinical features of saturnine gout are outlined. After describing the role of lead in renal insufficiency and purine metabolism, we conclude with a discussion of specific strategies to manage this clinically important form of secondary gout.

12 Review Genetics of hyperuricemia and gout: implications for the present and future. 2013

George, Ronald L / Keenan, Robert T. ·Division of Rheumatology and Immunology, Duke University School of Medicine, DUMC, NC 27710, USA. ·Curr Rheumatol Rep · Pubmed #23307580.

ABSTRACT: Gout is the most common inflammatory arthropathy and occurs in the setting of elevated serum urate levels. Gout is also known to be associated with multiple comorbidities including cardiovascular disease and the metabolic syndrome. Recent advances in research have increased our understanding and improved our knowledge of the pathophysiology of gout. Genome-wide association studies have permitted the identification of several new and common genetic factors that contribute to hyperuricemia and gout. Most of these are involved with the renal urate transport system (the uric acid transportasome), generally considered the most influential regulator of serum urate homeostasis. Thus far, SCL22A12, SCL2A9, and GLUT9 have been found to have the greatest variation and most influence on serum urate levels. However, genetics are only a part of the explanation in the development of hyperuricemia and gout. As results have been mixed, the role of known urate influential genes in gout's associated comorbidities remains unclear. Regardless, GWAS findings have expanded our understanding of the pathophysiology of hyperuricemia and gout, and will likely play a role in the development of future therapies and treatment of this ancient disease.

13 Review Safety of urate-lowering therapies: managing the risks to gain the benefits. 2012

Keenan, Robert T. ·Duke Gout and Crystal Arthropathies Clinic, Duke Specialty Infusion Center, Durham, NC 27710, USA. robert.keenan@duke.edu ·Rheum Dis Clin North Am · Pubmed #23137576.

ABSTRACT: Gout is a metabolic disorder of purine metabolism and uric acid elimination. Over time, acute gout can develop into a chronic, disabling arthropathy, often associated with multiple comorbidities. Gout patients have often been undertreated, partly because of the clinician's perceived risks of a therapy outweighing its potential benefits. The approval of new therapies to treat hyperuricemia in gout has led to a new understanding of gout management and medication safety regarding new and old therapies. This review focuses on potential safety issues of currently available urate-lowering therapies and outlines strategies to minimize risks so their benefits can be reached.

14 Review The rheumatology of gout. 2012

Sundy, John S. ·Duke Global Proof of Concept Research Program, Duke Clinical Research Institute, Durham, NC 27710, USA. john.sundy@duke.edu ·Adv Chronic Kidney Dis · Pubmed #23089276.

ABSTRACT: Gout is a metabolic disorder of purine metabolism with primary manifestations of acute and chronic arthritis and tophus formation. The prevalence of gout appears to be increasing and may affect up to 8 million people in the United States. The development of novel therapies for gout after a 40-year hiatus has opened new understanding of this disease. In addition to causing severe musculoskeletal pain, gout is associated with impaired quality of life, reduced functional status, and injury to joints. The quality of care for many patients with gout is unfortunately not in keeping with current guidelines. The approval of new therapies to treat hyperuricemia, such as febuxostat and pegloticase, has increased our knowledge of the challenges of adequately controlling the disease. Rather than providing a comprehensive overview of gout, this review focuses on new developments in the clinical aspects of gout and highlights advances in the drug therapy of gout.

15 Review Pegloticase for treating refractory chronic gout. 2012

George, R L / Sundy, J S. ·Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. ·Drugs Today (Barc) · Pubmed #22844655.

ABSTRACT: Gout is a metabolic disorder of excess uric acid accumulation that manifests clinically as inflammatory arthritis, chronic arthropathy and the formation of deposits of uric acid known as tophi. A primary objective of gout management is to reduce the excess urate burden by regular use of drugs that reduce serum urate levels. Conventional urate-lowering drugs available in the U.S. are allopurinol, febuxostat and probenecid. Some patients are intolerant to or unresponsive to urate-lowering therapies and, therefore, are said to have refractory gout. Recently, a polyethylene glycol-conjugated uricase, pegloticase, was approved for treating refractory gout. In recent clinical trials, pegloticase normalized plasma urate levels, reduced the size of tophi, and improved functional status and quality of life in patients with refractory disease. Immunogenicity to pegloticase is associated with loss of urate-lowering response and the risk of infusion reactions. Pegloticase is effective in treating hyperuricemia and the clinical manifestations of gout in patients who cannot be adequately managed with conventional therapy.

16 Review Gout, hyperuricemia, and the risk of cardiovascular disease: cause and effect? 2010

Shah, Ankoor / Keenan, Robert T. ·Division of Rheumatology and Immunology, Duke University School of Medicine, 301 Trent Drive, Durham, NC 27710, USA. ·Curr Rheumatol Rep · Pubmed #20425020.

ABSTRACT: Gout and hyperuricemia have long been suspected to be risk factors for cardiovascular disease. However, studies have frequently failed to distinguish whether these entities have an independent effect on cardiovascular risk or serve as markers for other risk factors. In vitro and animal studies suggest that uric acid is a biologically active compound that can increase inflammatory mediators known to lead to vascular damage. In contrast, uric acid also has potentially protective effects as a strong antioxidant, approaching the potency of vitamin C. Large clinical trials demonstrate a consistent relationship between elevated serum uric acid and a variety of cardiovascular diseases, although the strength of association varies greatly. We review the evidence for and against an independent role for hyperuricemia and/or gout in cardiovascular pathology.

17 Review Progress in the pharmacotherapy of gout. 2010

Sundy, John S. ·Division of Pulmonary Allergy and Critical Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. john.sundy@duke.edu ·Curr Opin Rheumatol · Pubmed #20110792.

ABSTRACT: PURPOSE OF REVIEW: To summarize new knowledge on approved and emerging drugs used to treat hyperuricemia or the clinical manifestations of gout. RECENT FINDINGS: Results of several clinical trials provide new data on the efficacy and safety of the approved urate-lowering drugs, allopurinol and febuxostat. New recommendations have been presented on appropriate dosing of colchicine for acute gout flares and potential toxicities of combining colchicine with medications such as clarithromycin. Emerging therapies, including pegloticase, the uricosuric agent RDEA596, and the interleukin-1 inhibitors, rilonacept and canakinumab, have shown promise in early and late phase clinical trials. SUMMARY: Recent publications demonstrate an opportunity to use existing gout therapies more effectively in order to improve both efficacy and safety. Emerging therapies for gout show promise for unmet needs in selected gout populations.

18 Clinical Trial Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). 2017

Bardin, Thomas / Keenan, Robert T / Khanna, Puja P / Kopicko, Jeff / Fung, Maple / Bhakta, Nihar / Adler, Scott / Storgard, Chris / Baumgartner, Scott / So, Alexander. ·Rhumatologie, Lariboisière Hospital, and Université Paris Diderot Sorbonne Cité, Paris, France. · Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA. · Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA. · Biometrics, Ardea Biosciences, Inc., San Diego, California, USA. · Research & Development, Ardea Biosciences, Inc., San Diego, California, USA. · Research & Development, AstraZeneca Pharmaceuticals, Gaithersburg, Maryland, USA. · Medical Affairs, Ardea Biosciences, Inc., San Diego, California, USA. · Service de rhumatologie, Université de Lausanne, Lausanne, Switzerland. ·Ann Rheum Dis · Pubmed #27821644.

ABSTRACT: OBJECTIVES: Determine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial. METHODS: Patients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data. RESULTS: Patients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively. CONCLUSION: Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy. TRIAL REGISTRATION NUMBER: NCT01493531.

19 Clinical Trial Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. 2016

Perez-Ruiz, Fernando / Sundy, John S / Miner, Jeffrey N / Cravets, Matthew / Storgard, Chris / Anonymous1230854. ·Rheumatology Division, Hospital Universitario Cruces, Barakaldo, Spain. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA Gilead Sciences, Foster City, California, USA. · Ardea Biosciences, San Diego, California, USA. · Ardea Biosciences, San Diego, California, USA Receptos, San Diego, California, USA. ·Ann Rheum Dis · Pubmed #26742777.

ABSTRACT: OBJECTIVES: To assess the efficacy and tolerability of lesinurad, an oral selective uric acid reabsorption inhibitor, in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol. METHODS: Patients (N=227) with an inadequate response to allopurinol, defined as serum urate (sUA) ≥6 mg/dL on ≥2 occasions ≥2 weeks apart despite ≥6 weeks of allopurinol, were randomised 2:1 to 4 weeks of double-blind treatment with lesinurad (200, 400 or 600 mg/day) or matching placebo in combination with their prestudy allopurinol dose (200-600 mg/day). Colchicine prophylaxis for gout flares was required. The primary end point was percent reduction from baseline sUA levels at 4 weeks. A pharmacokinetic substudy was also conducted. Safety was assessed throughout. RESULTS: Patients (n=208) received ≥1 dose of blinded medication. Lesinurad 200, 400 and 600 mg in combination with allopurinol produced significant mean percent reductions from baseline sUA of 16%, 22% and 30%, respectively, versus a mean 3% increase with placebo (p<0.0001, all doses vs placebo). Similar results were observed in patients with mild or moderate renal insufficiency (estimated creatinine clearance 30 to <90 mL/min). The incidence of ≥1 treatment-emergent adverse event was 46%, 48% and 54% with lesinurad 200, 400 and 600 mg, respectively, and 46% with placebo (most frequent, gout flares, arthralgia, headache and nasopharyngitis), with no deaths or serious adverse events. CONCLUSIONS: Lesinurad achieves clinically relevant and statistically significant reductions in sUA in combination with allopurinol in patients who warrant additional therapy on allopurinol alone. TRIAL REGISTRATION NUMBER: NCT01001338.

20 Clinical Trial Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. 2014

Sundy, John S / Schumacher, H Ralph / Kivitz, Alan / Weinstein, Steven P / Wu, Richard / King-Davis, Shirletta / Evans, Robert R. ·From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc. ·J Rheumatol · Pubmed #25028379.

ABSTRACT: OBJECTIVE: To evaluate the safety and efficacy of once-weekly subcutaneous rilonacept 160 mg for prevention of gout flares in patients initiating or continuing urate-lowering therapy (ULT). METHODS: This phase III study was conducted in the United States, South Africa, Europe, and Asia. Adults (n = 1315, 18-80 yrs) with gout, who were initiating or continuing ULT, were randomized to treatment with weekly subcutaneous injections of rilonacept 160 mg or placebo for 16 weeks followed by a 4-week safety followup. The primary endpoint was safety, assessed by adverse events (AE) and laboratory values. Efficacy was a secondary endpoint. RESULTS: Demographic and clinical characteristics were similar between treatments; predominantly male (87.8%), mean age 52.7 ± 11.3 years. Patients with ≥ 1 AE were 66.6% with rilonacept versus 59.1% placebo, with slightly more AE-related withdrawals with rilonacept (4.7% vs 3.0%) because of the greater incidence of injection site reactions (15.2% rilonacept, 3.3% placebo). Serious AE were similar in both groups, as were serious infections (0.9% placebo, 0.5% rilonacept); no tuberculosis or opportunistic infections occurred. Most common AE were headache, arthralgia, injection site erythema, accidental overdose, and pain in extremity. Of the 6 deaths, only 1 in the placebo group was considered treatment-related. At Week 16, rilonacept resulted in 70.3% fewer gout flares per patient (p < 0.0001), fewer patients with ≥ 1 and ≥ 2 gout flares (p < 0.0001), and 64.9% fewer gout flare days (p < 0.0001) relative to placebo. CONCLUSION: Weekly subcutaneous administration of rilonacept 160 mg showed no new safety signals. The safety profile was consistent with previous studies. Rilonacept also significantly reduced the risk of gout flares. Clinicaltrials.gov identifier NCT00856206; EudraCT No. 2008-007784-16.

21 Article Colorectal Cancer Among Gout Patients Undergoing Colonoscopy. 2019

Slobodnick, Anastasia / Krasnokutsky, Svetlana / Lehmann, Robert A / Keenan, Robert T / Quach, Jonathan / Francois, Fritz / Pillinger, Michael H. ·From the Section of Rheumatology, VA New York Harbor Health Care System, New York Campus. · Crystal Diseases Study Group, Division of Rheumatology, New York University School of Medicine, New York, NY. · Division of Rheumatology, Duke University School of Medicine, Durham, NC. · Section of Gastroenterology, VA New York Harbor Health Care System, New York Campus. · Division of Gastroenterology, New York University School of Medicine, New York, NY. ·J Clin Rheumatol · Pubmed #31764494.

ABSTRACT: BACKGROUND/OBJECTIVE: The connection between gout and various cancers remains unclear. We assessed the relationship between gout and colorectal cancer in a population of veterans. METHODS: We reviewed the Computerized Patient Record System of the VA New York Harbor Health Care System to assess the 10-year occurrence of colorectal cancer in patients with gout undergoing colonoscopy, versus patients with osteoarthritis but no gout. RESULTS: Gout and osteoarthritis subjects were similar in age, ethnicity, body mass index, and smoking history. Among 581 gout and 598 osteoarthritis subjects with documented colonoscopies, the 10-year prevalence of colorectal cancer was significantly lower in gout (0.8%) versus osteoarthritis (3.7%) (p = 0.0008) patients. Differences in colorectal cancer rates remained significant after stratifying for nonsteroidal anti-inflammatory drug use. Among gout subjects, use of colchicine and/or allopurinol, as well as the presence/absence of concomitant osteoarthritis, did not influence colorectal cancer occurrence. On subanalysis, differences in colorectal cancer occurrence between gout and osteoarthritis subjects persisted among those who underwent diagnostic (0.5% in gout vs 4.6% in osteoarthritis subjects, p < 0.001) but not screening (0.9% in gout subjects vs 1% in osteoarthritis subjects, p = 1.0) colonoscopy. There was no significant difference in nonmalignant colorectal polyp occurrence between gout and osteoarthritis subjects. CONCLUSIONS: Subjects with gout had decreased colonoscopy-documented occurrence of colorectal cancer compared with osteoarthritis subjects, suggesting a possible protective effect.

22 Article Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout. 2019

Bursill, David / Taylor, William J / Terkeltaub, Robert / Abhishek, Abhishek / So, Alexander K / Vargas-Santos, Ana Beatriz / Gaffo, Angelo Lino / Rosenthal, Ann / Tausche, Anne-Kathrin / Reginato, Anthony / Manger, Bernhard / Sciré, Carlo / Pineda, Carlos / van Durme, Caroline / Lin, Ching-Tsai / Yin, Congcong / Albert, Daniel Arthur / Biernat-Kaluza, Edyta / Roddy, Edward / Pascual, Eliseo / Becce, Fabio / Perez-Ruiz, Fernando / Sivera, Francisca / Lioté, Frédéric / Schett, Georg / Nuki, George / Filippou, Georgios / McCarthy, Geraldine / da Rocha Castelar Pinheiro, Geraldo / Ea, Hang-Korng / Tupinambá, Helena De Almeida / Yamanaka, Hisashi / Choi, Hyon K / Mackay, James / ODell, James R / Vázquez Mellado, Janitzia / Singh, Jasvinder A / Fitzgerald, John D / Jacobsson, Lennart T H / Joosten, Leo / Harrold, Leslie R / Stamp, Lisa / Andrés, Mariano / Gutierrez, Marwin / Kuwabara, Masanari / Dehlin, Mats / Janssen, Matthijs / Doherty, Michael / Hershfield, Michael S / Pillinger, Michael / Edwards, N Lawrence / Schlesinger, Naomi / Kumar, Nitin / Slot, Ole / Ottaviani, Sebastien / Richette, Pascal / MacMullan, Paul A / Chapman, Peter T / Lipsky, Peter E / Robinson, Philip / Khanna, Puja P / Gancheva, Rada N / Grainger, Rebecca / Johnson, Richard J / Te Kampe, Ritch / Keenan, Robert T / Tedeschi, Sara K / Kim, Seoyoung / Choi, Sung Jae / Fields, Theodore R / Bardin, Thomas / Uhlig, Till / Jansen, Tim / Merriman, Tony / Pascart, Tristan / Neogi, Tuhina / Klück, Viola / Louthrenoo, Worawit / Dalbeth, Nicola. ·Department of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia davebursill@bigpond.com. · Department of Medicine, University of Otago, Wellington, New Zealand. · Wellington Regional Rheumatology Unit, Hutt Valley District Health Board, Lower Hutt, New Zealand. · Department of Rheumatology, UCSD/ VA Medical Center, San Diego, California, USA. · Department of Academic Rheumatology, University of Nottingham, Nottingham, UK. · Department of Musculoskeletal Medicine, Service de RMR, Lausanne, Switzerland. · Department of Internal Medicine, Rheumatology Unit, State University of Rio de Janeiro, Rio de Janeiro, Brazil. · Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Division of Rheumatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. · Translational Research Unit, Clement J Zablocki VA Medical Center, Milwaukee, Wisconsin, USA. · Department of Rheumatology, University Hospital 'Carl Gustav Carus' of the Technical University Dresden, Dresden, Germany. · Division of Rheumatology, The Warren Alpert School of Medicine at Brown University, Providence, Rhode Island, USA. · Rheumatology and Immunology, Universität Erlangen-Nürnberg, Erlangen, Germany. · Section of Rheumatology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy. · Epidemiology Unit, Italian Society for Rheumatology, Milan, Italy. · Department of Rheumatology, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico. · Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre, Maastricht, The Netherlands. · Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan. · Department of Immunology and Dermatology, Henry Ford Health System, Detroit, Michigan, USA. · Department of Rheumatology, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire, USA. · Outpatient Rheumatology Clinic, Nutritional and Lifestyle Medicine Centre, ORLIK, Warsaw, Poland. · Research Institute for Primary Care and Health Sciences, Keele University, Keele, UK. · Department of Rheumatology, Hospital General Universitario de Alicante, Alicante, Spain. · Departamento de Medicina Clínica, Universidad Miguel Hernández, Alicante, Spain. · Department of Diagnostic and Interventional Radiology, University of Lausanne, Lausanne, Switzerland. · Rheumatology Division, Cruces University Hospital, Baracaldo, Spain. · Department of Medicine, University of the Basque Country, Biscay, Spain. · Investigation Group for Arthritis, Biocruces Health Research Institute, Baracaldo, Spain. · Department of Rheumatology, Hospital General Universitario Elda, Elda, Spain. · Department of Rhumatologie, Hôpital Lariboisière, Assistance Publique-Hopitaux de Paris, Paris, France. · Department of Rhumatologie, INSERM UMR-1132 and Université Paris Diderot, Paris, France. · Department of Internal Medicine III, Friedrich-Alexander University Erlangen-Nürnberg and Universitatsklinikum Erlangen, Erlangen, Germany. · Insititute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland. · School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. · Department of Rheumatology, Hôpital Lariboisière, Paris, France. · Rheumatology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. · Institute of Rheumatology, Tokyo Women's Medical University Hospital, Tokyo, Japan. · School of Medicine, Tokyo Women's Medical University, Tokyo, Japan. · Section of Rheumatology and Clinical Epidemiology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA. · President and CEO, Aristea Therapeutics, San Diego, California, USA. · Division of Rheumatology, University of Nebraska Medical Center, Omaha, Nebraska, USA. · Department of Rheumatology, Hospital General de Mexico and Universidad Nacional Autónoma de México, Mexico City, Mexico. · Department of Medicine at School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Medicine Service, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA. · Division of Epidemiology at School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Medicine/Rheumatology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA. · Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Department of Internal Medicine, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands. · Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA. · Chief Scientific Officer, Corrona, LLC, Southborough, Massachusetts, USA. · Department of Medicine, Otago University, Christchurch, New Zealand. · Department of Rheumatology, Hospital Universitario de Alicante, Alicante, Spain. · Division of Musculoskeletal and Rheumatic Diseases, Instituto Nacional Rehabilitación, México City, México. · Division of Renal Diseases and Hypertension, University of Colorado Denver School of Medicine, Aurora, Colorado, USA. · Department of Cardiology, Toranomon Hospital, Minato-ku, Japan. · Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Göteborg, Göteborg, Sweden. · Department of Rheumatology, VieCuri Medical Centre, Venlo, The Netherlands. · Division of Rheumatology, Duke University Medical Center, Durham, North Carolina, USA. · Department of Rheumatology/Medicine, New York University School of Medicine, New York City, New York, USA. · College of Medicine, University of Florida, Gainesville, Florida, USA. · Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. · Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Detroit, Michigan, USA. · Department of Rheumatology, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spinal Disorders, Rigshospitalet Glostrup, Glostrup, Denmark. · Department of Rheumatology, Bichat-Claude Bernard Hospital, University of Sorbonne Paris Cité, Paris, France. · Service de Rhumatologie, Hôpital Lariboisière, Assistance Publique-Hopitaux de Paris, and INSERM UMR-1132 and Université de Paris, Paris, France. · Division of Rheumatology, University of Calgary, Calgary, Alberta, Canada. · Department of Rheumatology, Immunology and Allergy, Canterbury District Health Board, Christchurch, New Zealand. · CEO and CMO, AMPEL BioSolutions, LLC, Charlottesville, Virginia, USA. · School of Clinical Medicine, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. · Department of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA. · Clinic of Rheumatology, University Hospital 'St. Ivan Rilski', Sofia, Bulgaria. · Department of Medicine, University of Otago, Wellington, Wellington, New Zealand. · Division of Renal Diseases and Hypertension, University of Colorado Denver, Denver, Colorado, USA. · Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA. · Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Arthritis Center, Harvard Medical School, Boston, Massachusetts, USA. · Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Ansan, South Korea. · Weill Cornell Medical College, Hospital for Special Surgery, New York City, New York, USA. · Department of Rheumatology, Hôpital Lariboisière, Assistance Publique-Hopitaux de Paris, and INSERM UMR-1132 and Université de Paris, Paris, France. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Rheumatology, Lille Catholic University, Saint-Philibert Hospital, Lomme, France. · Section of Rheumatology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. · Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. · Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. · Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. ·Ann Rheum Dis · Pubmed #31501138.

ABSTRACT: OBJECTIVE: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

23 Article Use of Pre-Infusion Serum Uric Acid Levels as a Biomarker for Infusion Reaction Risk in Patients on Pegloticase. 2019

Keenan, Robert T / Baraf, Herbert S B / LaMoreaux, Brian. ·Division of Rheumatology and Immunology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. · Arthritis and Rheumatism Associates, George Washington University, Wheaton, MD, USA. · Horizon Pharma, Lake Forest, IL, USA. blamoreaux@horizonpharma.com. ·Rheumatol Ther · Pubmed #30875075.

ABSTRACT: INTRODUCTION: The aim of this work is to evaluate the impact of the timing of pre-infusion serum uric acid (sUA) test results for use in applying stopping rules for pegloticase to identify patients at risk for infusion reactions (IRs) while on therapy. METHODS: Data from the phase 3 clinical trials of pegloticase were reviewed and individual uric acid levels of the 85 patients who received the approved regimen of biweekly infusions were examined in relation to the occurrence of IRs. RESULTS: Of the 22 patients (26%) who experienced an IR on pegloticase therapy without uric acid stopping rules, only seven (8%) would have had IRs if pegloticase therapy had been discontinued after two consecutive pre-infusion sUA levels above 6 mg/dl. If pegloticase therapy was stopped after a single pre-infusion sUA above 6 mg/dl, only two patients (2%) would have experienced IRs during the clinical studies. CONCLUSIONS: A pre-infusion sUA level functions as a highly accurate biomarker for identification of patients who are at risk of IRs while on pegloticase therapy. Stopping pegloticase in patients who have a rise in pre-infusion uric acid levels to above 6 mg/dl while on therapy would result in most IRs being avoided. FUNDING: Horizon Pharma.

24 Article Antioxidant properties of citric acid interfere with the uricase-based measurement of circulating uric acid. 2019

Ryan, Evan M / Duryee, Michael J / Hollins, Andrew / Dover, Susan K / Pirruccello, Samuel / Sayles, Harlan / Real, Kevin D / Hunter, Carlos D / Thiele, Geoffrey M / Mikuls, Ted R. ·Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA. · Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA; Veteran Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA. Electronic address: mduryee@unmc.edu. · Department of Clinical Sciences, Surgery, Duke University, Durham, NC, USA. · Veteran Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA. · Department of Clinical Pathology, University of Nebraska Medical Center, Omaha, NE, USA. · Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA; Veteran Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA. ·J Pharm Biomed Anal · Pubmed #30447534.

ABSTRACT: BACKGROUND: Circulating uric acid (UA) is an important biomarker, not only in the detection and management of gout, but also in assessing the risk of related comorbidity. The impact of collection methods on clinical UA measurements has been the subject of limited study. After observing significant differences between UA concentrations of blood samples obtained by different collection tubes, we began examining the effects of exogenous tube components on measured UA concentrations. We aimed to: (1) demonstrate the variability in uricase-based UA measurements attributable to different collection methods and (2) identify factors influencing this variability. METHODS: Blood samples from human subjects were collected using Serum Separator Tubes (SST tubes), Acid Citrate Dextrose (ACD) tubes, and Sodium Citrate (SC) tubes. Circulating UA concentrations were measured by chemistry analyzers utilizing the uricase method. Absorbance assays were run in order to determine the effects of citric acid, sodium citrate, and dextrose on measured absorbance in the presence of leuco crystal violet dye, hydrogen peroxide, and peroxidase. Statistical analyses-including Student's T tests and ANOVA-were used to compare results. RESULTS: UA concentrations of blood samples collected in ACD tubes were significantly lower than those collected in SST tubes (P < 0.01). Samples collected in SC tubes trended towards lower UA measurements than samples collected in SST tubes, although this difference did not reach statistical significance (P = 0.06). Blood samples spiked with separate concentrations of sodium citrate (3.2 and 22.0 g/L), citric acid (8.0 g/L), and dextrose (24.5 g/L) demonstrated significantly lower UA measurements compared to controls (P < 0.01). Absorbance assays demonstrated that increasing concentrations of citric acid and sodium citrate-in the presence of leuco crystal violet, hydrogen peroxide, and peroxidase-decreased the amount of oxidized dye in the uricase method of UA measurement in a dose-dependent manner (P < 0.01). In contrast, dextrose did not significantly alter the amount of oxidized dye available. DISCUSSION: Our results indicate that citric acid obstructs accurate uricase-based UA measurement, providing falsely low values. Citric acid, a known antioxidant, scavenges hydrogen peroxide, a key intermediate using the uricase method. By scavenging hydrogen peroxide, citric acid decreases the amount of oxidized leuco dye leading to falsely low UA measurements. Therefore, collection tubes, like ACD and SC tubes, which contain concentrations of citric acid or its conjugate base sodium citrate should not be used to measure circulating UA levels when utilizing uricase-based measurement methods.

25 Article Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout. 2019

Bursill, David / Taylor, William J / Terkeltaub, Robert / Kuwabara, Masanari / Merriman, Tony R / Grainger, Rebecca / Pineda, Carlos / Louthrenoo, Worawit / Edwards, N Lawrence / Andrés, Mariano / Vargas-Santos, Ana Beatriz / Roddy, Edward / Pascart, Tristan / Lin, Ching-Tsai / Perez-Ruiz, Fernando / Tedeschi, Sara K / Kim, Seoyoung C / Harrold, Leslie R / McCarthy, Geraldine / Kumar, Nitin / Chapman, Peter T / Tausche, Anne-Kathrin / Vazquez-Mellado, Janitzia / Gutierrez, Marwin / da Rocha Castelar-Pinheiro, Geraldo / Richette, Pascal / Pascual, Eliseo / Fisher, Mark C / Burgos-Vargas, Ruben / Robinson, Philip C / Singh, Jasvinder A / Jansen, Tim L / Saag, Kenneth G / Slot, Ole / Uhlig, Tillmann / Solomon, Daniel H / Keenan, Robert T / Scire, Carlo Alberto / Biernat-Kaluza, Edyta / Dehlin, Mats / Nuki, George / Schlesinger, Naomi / Janssen, Matthijs / Stamp, Lisa K / Sivera, Francisca / Reginato, Anthony M / Jacobsson, Lennart / Lioté, Frédéric / Ea, Hang-Korng / Rosenthal, Ann / Bardin, Thomas / Choi, Hyon K / Hershfield, Michael S / Czegley, Christine / Choi, Sung Jae / Dalbeth, Nicola. ·University of Auckland, Auckland, New Zealand, and Adelaide Medical School, University of Adelaide, South Australia, Australia. · University of Otago, Wellington, and Hutt Valley District Health Board, Lower Hutt, New Zealand. · Veterans Affairs Medical Center and University of California, San Diego. · Toranomon Hospital, Tokyo, Japan, and University of Colorado Denver, Aurora. · University of Otago, Dunedin, New Zealand. · Instituto Nacional Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico. · Chiang Mai University, Chiang Mai, Thailand. · University of Florida College of Medicine, Gainesville. · Hospital Universitario de Alicante and Universidad Miguel Hernández, Alicante, Spain. · State University of Rio de Janeiro, Rio de Janeiro, Brazil. · Keele University, Keele, UK. · Lille Catholic University and Saint-Philibert Hospital, Lomme, France. · Taichung Veterans General Hospital, Taichung, Taiwan. · University of the Basque Country, Biscay, and Cruces University Hospital and Biocruces Health Research Institute, Baracaldo, Spain. · Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts. · Corrona, LLC, Waltham, and University of Massachusetts Medical School, Worcester. · Mater Misericordiae University Hospital and University College, Dublin, Ireland. · Henry Ford Hospital, Detroit, Michigan. · Christchurch Hospital, Christchurch, New Zealand. · University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. · Hospital General de México and Universidad Nacional Autónoma de México, Mexico City, Mexico. · Instituto Nacional Rehabilitación, Mexico City, Mexico. · Hôpital Lariboisière, Assistance Publique-Hopitaux de Paris, and INSERM UMR-1132 and Université Paris Diderot, Paris, France. · Harvard Medical School and Massachusetts General Hospital Boston. · University of Queensland School of Medicine and Royal Brisbane and Women's Hospital, Herston, Queensland, Australia. · Veterans Affairs Medical Center, Birmingham, and University of Alabama at Birmingham. · Viecuri Medical Centre, Venlo, The Netherlands. · University of Alabama at Birmingham. · Rigshospitalet Glostrup, Glostrup, Denmark. · Diakonhjemmet Hospital, Oslo, Norway. · Duke University School of Medicine, Durham, North Carolina. · University of Ferrara, Ferrara, and Italian Society for Rheumatology, Milan, Italy. · ORLIK, Warsaw, Poland. · Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · University of Edinburgh, Edinburgh, UK. · Rutgers-Robert Wood Johnson Medical School, Piscataway, New Jersey. · University of Otago, Christchurch, New Zealand. · Hospital General Universitario de Elda, Alicante, Spain. · Warren Alpert School of Medicine at Brown University, Providence, Rhode Island. · Medical College of Wisconsin and the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee. · Duke University Medical Center, Durham, North Carolina. · Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. · University of California, San Diego, and Korea University Ansan Hospital, Ansan, South Korea. · University of Auckland, Auckland, New Zealand. ·Arthritis Care Res (Hoboken) · Pubmed #29799677.

ABSTRACT: OBJECTIVE: The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. METHODS: Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. RESULTS: There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (≥80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. CONCLUSION: Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.

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