Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Gout: HELP
Articles by John S. Sundy
Based on 25 articles published since 2008
||||

Between 2008 and 2019, J. Sundy wrote the following 25 articles about Gout.
 
+ Citations + Abstracts
1 Editorial A natural experiment in the quality of care in gout. 2010

Sundy, John S. · ·Curr Opin Rheumatol · Pubmed #20110791.

ABSTRACT: -- No abstract --

2 Editorial Gout management: let's get it right this time. 2008

Sundy, John S. · ·Arthritis Rheum · Pubmed #18975368.

ABSTRACT: -- No abstract --

3 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.

4 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.

5 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.

6 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.

7 Review Refractory gout: what is it and what to do about it? 2008

Fels, Edward / Sundy, John S. ·Departments of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. ·Curr Opin Rheumatol · Pubmed #18349751.

ABSTRACT: PURPOSE OF REVIEW: The purpose of this review is to discuss the defining characteristics of refractory gout and the pharmacological management of this problem. RECENT FINDINGS: Refractory gout refers to those patients who have ongoing symptoms of active disease and cannot maintain a target serum urate less than 6 mg/dl. Patients with refractory gout have reduced quality of life, functional impairment, and joint destruction. Multiple factors contribute to refractory gout, and they often relate to delayed or insufficient dosing with allopurinol. Chronic kidney disease imparts a dose limitation on allopurinol that further impairs the effectiveness of urate-lowering therapy. Febuxostat, a novel xanthine oxidase inhibitor, represents a potential alternative to allopurinol in refractory gout patients. Uricase, the enzyme that catalyzes conversion of uric acid into allantoin, is showing promise with its ability to rapidly diminish serum urate levels. The recently defined role of the NALP3 inflammasome in the inflammatory phase of gout suggests a potential role for interleukin-1 inhibition in urate crystal-induced inflammation. SUMMARY: Refractory gout occurs when urate levels are not adequately controlled. Emerging therapies may improve the clinical course of patients with recalcitrant disease.

8 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 / Anonymous791036. ·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.

9 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.

10 Clinical Trial Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients. 2014

Hershfield, Michael S / Ganson, Nancy J / Kelly, Susan J / Scarlett, Edna L / Jaggers, Denise A / Sundy, John S. · ·Arthritis Res Ther · Pubmed #24602182.

ABSTRACT: INTRODUCTION: Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single doses of pegloticase unexpectedly induced antibodies (Ab) that bound to polyethylene glycol (PEG). We have conducted a phase 2 trial to evaluate every 3-week dosing, and to further define the Ab response to pegloticase. Organ transplant recipients were included, as they are prone to severe gout that is difficult to manage, and because treatment to prevent graft rejection might influence the immune response to pegloticase. METHODS: Plasma uricase activity (pUox), urate concentration (pUA), and clinical response were monitored during up to 5 infusions in 30 patients, including 7 organ transplant recipients. Depending on whether pUA <6 mg/dL was achieved and maintained, patients were classified as non (NR), persistent (PR), or transient (TR) responders. Ab to pegloticase and 10 kDa mPEG were monitored by enzyme linked immunosorbent assay and specificity was further defined. RESULTS: We observed 17 PR, 12 TR, and 1 NR; 21 patients (16 PR, 5 TR) received all 5 infusions. Over the 15-week trial, pUA in PR averaged 1.0 ± 0.4 mg/dL; T½ for pUox was approximately 13 days, and area under the curve after dose 5 was approximately 30% higher than after dose 1. PR showed clinical benefit and in some, tophi resolved. In 11 of 12 TR, pUox fell rapidly and hyperuricemia recurred before dose 2. In all TR and NR, loss of response to pegloticase was accompanied by Ab to PEG, which was pre-existing in half of those who had no prior exposure to pegloticase. No PR, and 1 one out of 7 organ transplant recipients, had a sustained Ab response to pegloticase. CONCLUSIONS: Every 3-week dosing is effective and may enhance the utility of pegloticase for treating refractory gout. Ab to PEG, which were pre-existing or induced by treatment, caused rapid loss of efficacy and increased the risk of infusion reactions. Organ transplant recipients can benefit from pegloticase, and may be less prone than non-recipients to developing anti-PEG Ab. Investigation of immunosuppressive strategies to minimize anti-PEG Ab is warranted. TRIAL REGISTRATION: ClincalTrials.gov identifier: NCT00111657.

11 Clinical Trial Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. 2013

Baraf, Herbert S B / Becker, Michael A / Gutierrez-Urena, Sergio R / Treadwell, Edward L / Vazquez-Mellado, Janitzia / Rehrig, Claudia D / Ottery, Faith D / Sundy, John S / Yood, Robert A. · ·Arthritis Res Ther · Pubmed #24286509.

ABSTRACT: INTRODUCTION: Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy. METHODS: Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR. RESULTS: Among 212 patients randomized in the RCTs, 155 (73%) had ≥ 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo). CONCLUSIONS: Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy. TRIAL REGISTRATIONS: NCT00325195, NCT01356498.

12 Clinical Trial Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial. 2012

Schumacher, H Ralph / Sundy, John S / Terkeltaub, Robert / Knapp, Howard R / Mellis, Scott J / Stahl, Neil / Yancopoulos, George D / Soo, Yuhwen / King-Davis, Shirletta / Weinstein, Steven P / Radin, Allen R / Anonymous5280714. ·University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA. schumacr@mail.med.upenn.edu ·Arthritis Rheum · Pubmed #22223180.

ABSTRACT: OBJECTIVE: To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy. METHODS: In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained. RESULTS: Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015). CONCLUSION: The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.

13 Clinical Trial Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: results of a phase II randomized study. 2008

Sundy, John S / Becker, Michael A / Baraf, Herbert S B / Barkhuizen, Andre / Moreland, Larry W / Huang, William / Waltrip, Royce W / Maroli, Allan N / Horowitz, Zeb / Anonymous38290607. ·Duke University Medical Center, Durham, North Carolina 27710, USA. john.sundy@duke.edu ·Arthritis Rheum · Pubmed #18759308.

ABSTRACT: OBJECTIVE: To assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase. METHODS: Forty-one patients were randomized to undergo 12-14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded. RESULTS: The mean plasma urate level was reduced to Pegloticase, administered in multiple doses, was effective in rapidly reducing and maintaining plasma urate levels at

14 Article 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 2015

Neogi, Tuhina / Jansen, Tim L Th A / Dalbeth, Nicola / Fransen, Jaap / Schumacher, H Ralph / Berendsen, Dianne / Brown, Melanie / Choi, Hyon / Edwards, N Lawrence / Janssens, Hein J E M / Lioté, Frédéric / Naden, Raymond P / Nuki, George / Ogdie, Alexis / Perez-Ruiz, Fernando / Saag, Kenneth / Singh, Jasvinder A / Sundy, John S / Tausche, Anne-Kathrin / Vaquez-Mellado, Janitzia / Yarows, Steven A / Taylor, William J. ·Boston University School of Medicine, Boston, Massachusetts, USA. · Viecuri Medical Center, Venlo, The Netherlands Radboud University Medical Center, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · Radboud University Medical Center, Nijmegen, The Netherlands. · University of Pennsylvania, Philadelphia, Pennsylvania, USA. · University of Otago, Wellington, New Zealand. · University of Florida, Gainesville, Florida, USA. · INSERM UMR 1132, Hôpital Lariboisière, AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · McMaster University Medical Centre, Hamilton, Ontario, Canada. · University of Edinburgh, Edinburgh, UK. · Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya, Spain. · University of Alabama at Birmingham, Birmingham, Alabama, USA. · Birmingham VA Medical Center and University of Alabama at Birmingham, and Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Duke University and Duke University Medical Center, Durham, North Carolina, USA Gilead Sciences, Foster City, California, USA. · University Hospital Carl Gustav Carus, Dresden, Germany. · Hospital General de Mexico, Mexico City, Mexico. · University of Michigan Health System, Chelsea. ·Ann Rheum Dis · Pubmed #26359487.

ABSTRACT: OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

15 Article 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 2015

Neogi, Tuhina / Jansen, Tim L Th A / Dalbeth, Nicola / Fransen, Jaap / Schumacher, H Ralph / Berendsen, Dianne / Brown, Melanie / Choi, Hyon / Edwards, N Lawrence / Janssens, Hein J E M / Lioté, Frédéric / Naden, Raymond P / Nuki, George / Ogdie, Alexis / Perez-Ruiz, Fernando / Saag, Kenneth / Singh, Jasvinder A / Sundy, John S / Tausche, Anne-Kathrin / Vazquez-Mellado, Janitzia / Yarows, Steven A / Taylor, William J. ·Boston University School of Medicine, Boston, Massachusetts. · Viecuri Medical Center, Venlo, The Netherlands, and Radboud University Medical Center, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · Radboud University Medical Center, Nijmegen, The Netherlands. · University of Pennsylvania, Philadelphia. · University of Otago, Wellington, New Zealand. · University of Florida, Gainesville. · Frédéric Lioté, MD, PhD: INSERM UMR 1132, Hôpital Lariboisière, AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · McMaster University Medical Centre, Hamilton, Ontario, Canada. · University of Edinburgh, Edinburgh, UK. · Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya, Spain. · University of Alabama at Birmingham. · Birmingham VA Medical Center and University of Alabama at Birmingham, and Mayo Clinic College of Medicine, Rochester, Minnesota. · Gilead Sciences, Foster City, California). · University Hospital Carl Gustav Carus, Dresden, Germany. · Hospital General de Mexico, Mexico City, Mexico. · University of Michigan Health System, Chelsea. ·Arthritis Rheumatol · Pubmed #26352873.

ABSTRACT: OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSION: The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

16 Article Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout. 2014

Lipsky, Peter E / Calabrese, Leonard H / Kavanaugh, Arthur / Sundy, John S / Wright, David / Wolfson, Marsha / Becker, Michael A. · ·Arthritis Res Ther · Pubmed #24588936.

ABSTRACT: INTRODUCTION: The efficacy of pegloticase, a polyethylene glycol (PEG)-conjugated mammalian recombinant uricase, approved for chronic refractory gout, can be limited by the development of antibodies (Ab). Analyses from 2 replicate, 6-month, randomized controlled trials were performed to characterize Ab responses to pegloticase. METHODS: Anti-pegloticase, anti-PEG, and anti-uricase Ab were determined by validated enzyme-linked immunosorbent assays. Ab titers were analyzed for possible relationships with serum pegloticase concentrations, serum uric acid (sUA) lowering, and risk of infusion reactions (IRs). RESULTS: Sixty-nine (41%) of 169 patients receiving pegloticase developed high titer anti-pegloticase Ab (> 1:2430) and 40% (67/169) developed anti-PEG Ab; 1 patient receiving placebo developed high titer anti-pegloticase Ab. Only 14% (24/169) of patients developed anti-uricase Ab, usually at low titer. In responders, patients showing sustained UA lowering, mean anti-pegloticase titers at week 25 (1:837 ± 1687 with biweekly and 1:2025 ± 4506 with monthly dosing) were markedly lower than in nonresponders (1:34,528 ± 42,228 and 1:89,658 ± 297,797, respectively). Nonresponder status was associated with reduced serum pegloticase concentrations. Baseline anti-pegloticase Ab, evident in 15% (31/212) of patients, did not predict subsequent loss of urate-lowering response. Loss of sUA response preceded IRs in 44 of 56 (79%) pegloticase-treated patients. CONCLUSIONS: Loss of responsiveness to pegloticase is associated with the development of high titer anti-pegloticase Ab that increase clearance of pegloticase and are associated with a loss of the sUA lowering effect and increased IR risk. Pre-infusion sUA can be used as a surrogate for the presence of deleterious anti-pegloticase Ab. TRIAL REGISTRATION: NCT00325195. Registered 10 May 2006, NCT01356498. Registered 27 October 2008.

17 Article OMERACT endorsement of measures of outcome for studies of acute gout. 2014

Singh, Jasvinder A / Taylor, William J / Dalbeth, Nicola / Simon, Lee S / Sundy, John / Grainger, Rebecca / Alten, Rieke / March, Lyn / Strand, Vibeke / Wells, George / Khanna, Dinesh / McQueen, Fiona / Schlesinger, Naomi / Boonen, Annelies / Boers, Maarten / Saag, Kenneth G / Schumacher, H Ralph / Edwards, N Lawrence. ·From Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Medicine, University of Otago, Wellington; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; SDG LLC, Cambridge, Massachusetts,; Duke University School of Medicine, Durham, North Carolina, USA, and Duke-National University of Singapore Graduate Medical School, Singapore; Schlosspark-Klinik Teaching Hospital of the Charité, University Medicine Berlin, Berlin, Germany; University of Sydney Institute of Bone and Joint Research and Department of Rheumatology, Royal North Shore Hospital, Sydney, Australia; Stanford University Division of Immunology and Rheumatology, Portolo Valley, California, USA; University of Ottawa, London, Ontario, Canada; University of Michigan Medical School, Ann Arbor, Michigan, USA; University of Auckland, Department of Molecular Medicine and Pathology, Grafton, Auckland, New Zealand; Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA; Maastricht University Medical Center, Division of Rheumatology, and Caphri Research Institute, University Maastricht; VU University Medical Center, Amsterdam, the Netherlands; University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Rheumatology, University of Florida, Gainsville, Florida, USA. ·J Rheumatol · Pubmed #24334651.

ABSTRACT: OBJECTIVE: To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements of truth, discrimination, and feasibility; and where future research efforts need to be directed. METHODS: Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted "don't know"). RESULTS: The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed. CONCLUSION: Measures of pain, joint swelling, joint tenderness, and patient global assessment in acute gout were endorsed at OMERACT 11. These measures should now be used in clinical trials of acute gout.

18 Article Exploratory study of radiographic change in patients with tophaceous gout treated with intensive urate-lowering therapy. 2014

Dalbeth, Nicola / Doyle, Anthony J / McQueen, Fiona M / Sundy, John / Baraf, Herbert S B. ·University of Auckland, Auckland, New Zealand. ·Arthritis Care Res (Hoboken) · Pubmed #23836458.

ABSTRACT: OBJECTIVE: Tophi are strongly associated with structural damage in gout, and urate-lowering therapy reduces tophus size. Pegloticase leads to dramatic reductions in serum urate and subcutaneous tophi in treatment responders. The aim of this analysis was to examine whether profound urate lowering can alter radiographic findings in gout. METHODS: Serial plain radiographs of the hands and feet were obtained from 8 patients with tophaceous gout treated with pegloticase. Radiographs were scored for erosion and joint space narrowing (JSN) according to the gout-modified Sharp/van der Heijde method. Scorers were blinded to each other's scores and to the clinical characteristics of the patients (including the clinical response to pegloticase). A detailed qualitative site-by-site analysis was undertaken to define additional changes observed from baseline. RESULTS: All patients experienced a profound urate-lowering response (serum urate level <1 mg/dl) during pegloticase treatment. For the entire group, the median total radiographic scores reduced from 69.25 (range 1.5-138) at baseline to 57.25 (range 1.5-110) at 12 months (P = 0.02). Median erosion scores reduced over 1 year (P = 0.008), but JSN scores did not change (P = 0.50). Further reductions were observed in total scores and erosion scores in 5 patients with 24-month followup films (one-way analysis of variance P = 0.009 for total score, 0.02 for erosion, and 0.95 for JSN). Qualitative site-by-site analysis identified regression of soft tissue masses, increased sclerosis, and filling in of erosions in the followup films. CONCLUSION: This exploratory study suggests that profound urate lowering can lead to improvement in structural damage, particularly bone erosion, in patients with tophaceous gout.

19 Article Long-term safety of pegloticase in chronic gout refractory to conventional treatment. 2013

Becker, Michael A / Baraf, Herbert S B / Yood, Robert A / Dillon, Aileen / Vázquez-Mellado, Janitzia / Ottery, Faith D / Khanna, Dinesh / Sundy, John S. ·Rheumatology Section, The University of Chicago, Chicago, IL 60611-1713, USA. mbecker@medicine.bsd.uchicago.edu ·Ann Rheum Dis · Pubmed #23144450.

ABSTRACT: OBJECTIVE: To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout. METHODS: This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy. RESULTS: Patients (n=149) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained <6 mg/dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence. CONCLUSIONS: The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment.

20 Article Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. 2011

Sundy, John S / Baraf, Herbert S B / Yood, Robert A / Edwards, N Lawrence / Gutierrez-Urena, Sergio R / Treadwell, Edward L / Vázquez-Mellado, Janitzia / White, William B / Lipsky, Peter E / Horowitz, Zeb / Huang, William / Maroli, Allan N / Waltrip, Royce W / Hamburger, Steven A / Becker, Michael A. ·Duke Clinical Research Unit, Duke University Medical Center, Durham, North Carolina, USA. ·JAMA · Pubmed #21846852.

ABSTRACT: CONTEXT: Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. OBJECTIVE: To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. DESIGN, SETTING, AND PATIENTS: Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. INTERVENTION: Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). MAIN OUTCOME MEASURE: Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. RESULTS: In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). CONCLUSION: Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00325195.

21 Article Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy. 2011

Edwards, N L / Sundy, J S / Forsythe, A / Blume, S / Pan, F / Becker, M A. ·Department of Rheumatology, University of Florida, Gainesville, FL, USA. ·J Med Econ · Pubmed #21138339.

ABSTRACT: OBJECTIVE: Joint pain and swelling during gout flares may lead to considerable morbidity and disability, having an impact on patient work productivity and social participation. The objective of this study was to assess how gout flares affect these activities in patients with chronic gout refractory to conventional therapy. METHODS: A 1-year prospective observational study was conducted among patients with symptomatic disease in the United States in 2001. Inclusion criteria required patients (1) to be age 18 years or older, (2) to have documented, crystal-proven gout, (3) to have symptomatic gout, and (4) to be intolerant or unresponsive to conventional therapy, reflected by SUA ≥ 6.0 mg/dL. Patients were evaluated every 2 months. At each visit, patients completed a gout diary, which included number of flares experienced, duration and severity of each flare, and whether the flare caused: (1) work loss, (2) missed appointments or social events, or (3) impairment of self-care activities. The Short-Form Health Survey (SF-36) was also completed each visit. RESULTS: Analyses were restricted to those who completed the first 6 months of the study (n = 81). Mean number of flares per patient per year was 8.8. Of the patients who were <65 years, 78% reported at least 1 work day lost due to a gout attack during the year. Mean annual work day loss for those <65 years was 25.1 days. A total of 545 of patients reported at least one flare per year that impaired social activities, with a mean of 17.1 social days lost and 52% reported at least one flare per year that compromised normal self-care activities, with a mean of 16.9 days impairment. Correlations between the diary reports and activity-related questions from the SF-36 were significantly positive. LIMITATIONS: The study is limited by small sample size, lack of reference group, and inability to explicitly collect employment information. Age under 65 years was used as a proxy for employment eligibility. CONCLUSION: Flares in patients with chronic gout refractory to conventional therapy significantly affect patient work productivity and social activities.

22 Article Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo. 2010

Hershfield, Michael S / Roberts, L Jackson / Ganson, Nancy J / Kelly, Susan J / Santisteban, Ines / Scarlett, Edna / Jaggers, Denise / Sundy, John S. ·Division of Rheumatology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. msh@biochem.duke.edu ·Proc Natl Acad Sci U S A · Pubmed #20660758.

ABSTRACT: A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associations. Pegloticase therapy generates H(2)O(2) while depleting urate, offering an in vivo test of the antioxidant hypothesis. We show that erythrocytes can efficiently eliminate H(2)O(2) derived from urate oxidation to prevent cell injury in vitro; during therapy, disulfide-linked peroxiredoxin 2 dimer did not accumulate in red blood cells, indicating that their peroxidase capacity was not exceeded. To assess oxidative stress, we monitored F2-Isoprostanes (F2-IsoPs) and protein carbonyls (PC), products of arachidonic acid and protein oxidation, in plasma of 26 refractory gout patients receiving up to five infusions of pegloticase at 3-wk intervals. At baseline, PUA was markedly elevated in all patients, and plasma F2-IsoP concentration was elevated in most. Pegloticase infusion rapidly lowered mean PUA to < or = 1 mg/dL in all patients, and PUA remained low in 16 of 21 patients who completed treatment. F2-IsoP levels did not correlate with PUA and did not increase during 15 wk of sustained urate depletion. There also was no significant change in the levels of plasma PC. Because refractory gout is associated with high oxidative stress in spite of high PUA, and profoundly depleting uric acid did not increase lipid or protein oxidation, we conclude that urate is not a major factor controlling oxidative stress in vivo.

23 Article Preventing and treating acute gout attacks across the clinical spectrum: a roundtable discussion. 2010

Mandell, Brian F / Edwards, N Lawrence / Sundy, John S / Simkin, Peter A / Pile, James C. ·Center for Vasculitis Care and Research, Department of Rheumatic and Immunologic Disease, Cleveland Clinic, Cleveland, OH 44195, USA. mandelb@ccf.org ·Cleve Clin J Med · Pubmed #20516241.

ABSTRACT: -- No abstract --

24 Article The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study. 2009

Terkeltaub, R / Sundy, J S / Schumacher, H R / Murphy, F / Bookbinder, S / Biedermann, S / Wu, R / Mellis, S / Radin, A. ·VAMC Rheumatology, 111K, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. rterkeltaub@ucsd.edu ·Ann Rheum Dis · Pubmed #19635719.

ABSTRACT: BACKGROUND: Recent studies suggest that blockade of the NLRP3 (cryopyrin) inflammasome interleukin 1beta (IL1beta) pathway may offer a new treatment strategy for gout. OBJECTIVE: To explore the potential utility of rilonacept (IL1 Trap) in patients with chronic active gouty arthritis in a proof-of-concept study. METHODS: This 14-week, multicentre, non-randomised, single-blind, monosequence crossover study of 10 patients with chronic active gouty arthritis included a placebo run-in (2 weeks), active rilonacept treatment (6 weeks) and a 6-week post-treatment follow-up. RESULTS: Rilonacept was generally well tolerated. No deaths and no serious adverse events occurred during the study. One patient withdrew owing to an injection-site reaction. Patients' self-reported median pain visual analogue scale scores significantly decreased from week 2 (after the placebo run-in) to week 4 (2 weeks of rilonacept) (5.0 to 2.8; p<0.049), with sustained improvement at week 8 (1.3; p<0.049); 5 of 10 patients reported at least a 75% improvement. Median symptom-adjusted and severity-adjusted joint scores were significantly decreased. High-sensitivity C-reactive protein levels fell significantly. CONCLUSIONS: This proof-of-concept study demonstrated that rilonacept is generally well tolerated and may offer therapeutic benefit in reducing pain in patients with chronic refractory gouty arthritis, supporting the need for larger, randomised, controlled studies of IL1 antagonism such as with rilonacept for this clinical indication.

25 Article Quality of life and disability in patients with treatment-failure gout. 2009

Becker, Michael A / Schumacher, H Ralph / Benjamin, Katy L / Gorevic, Peter / Greenwald, Maria / Fessel, Jeffrey / Edwards, Lawrence / Kawata, Ariane K / Frank, Lori / Waltrip, Royce / Maroli, Allan / Huang, Bill / Anonymous39370625 / Sundy, John S. ·Division of Biological Sciences, Rheumatology Section, University of Chicago, Chicago, IL, USA. ·J Rheumatol · Pubmed #19332629.

ABSTRACT: OBJECTIVE: The relationship between self-reported quality of life and disability and disease severity was evaluated in subjects with treatment-failure gout (n = 110) in a prospective, 52-week, observational study. METHODS: Subjects had symptomatic crystal-proven gout of at least 2 years' duration and intolerance or refractoriness to conventional urate-lowering therapy. Serum uric acid (sUA) concentration, swollen and tender joint counts, frequency and severity of gout flares, tophus assessments, comorbidities, and patient-reported outcomes data [Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire-Damage Index] were collected. Analyses included correlations of patient-reported outcomes with clinical variables and changes in clinical status. RESULTS: Mean age of study subjects was 59 years. Mean scores on SF-36 physical functioning subscales were 34.2-46.8, analogous to persons aged >or= 75 years in the general population. Subjects with more severe gout at baseline had worse health-related quality of life (HRQOL) in all areas (p < 0.02 for all measures), compared to patients with mild-moderate disease. Number of flares reported in past year, number of tender joints, swollen joints, and tophi correlated significantly with some or all HRQOL and disability measures. sUA was not significantly correlated with any HRQOL or disability measure. Subjects with comorbidities experienced worse physical, but not mental, functioning. CONCLUSION: Severe gout is associated with poor HRQOL and disability, especially for patients who experience more gout flares and have a greater number of involved joints. Subject perceptions of gout-related functioning and pain severity appear to be highly sensitive indicators of HRQOL and disability.