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Gout: HELP
Articles by Kenneth G. Saag
Based on 24 articles published since 2009
(Why 24 articles?)
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Between 2009 and 2019, K. Saag wrote the following 24 articles about Gout.
 
+ Citations + Abstracts
1 Review Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN). 2017

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

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

2 Review Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link? 2009

Gaffo, Angelo L / Edwards, N Lawrence / Saag, Kenneth G. ·Birmingham VA Medical Center, 700 19th St. S, Birmingham, AL 35233, USA. agaffo@uab.edu ·Arthritis Res Ther · Pubmed #19725932.

ABSTRACT: An association between high levels of serum urate and cardiovascular disease has been proposed for many decades. However, it was only recently that compelling basic science data, small clinical trials, and epidemiological studies have provided support to the idea of a true causal effect. In this review we present recently published data that study the association between hyperuricemia and selected cardiovascular diseases, with a final conclusion about the possibility of this association being causal.

3 Clinical Trial Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study. 2018

Gunawardhana, Lhanoo / Becker, Michael A / Whelton, Andrew / Hunt, Barbara / Castillo, Majin / Saag, Kenneth. ·Takeda Pharmaceuticals, One Takeda Parkway, Deerfield, IL, 60015, USA. lhanoo.gunawardhana@takeda.com. · University of Chicago Pritzker School of Medicine, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA. · Johns Hopkins University, 1737 Beaver Brook Lane, Hunt Valley, MD, 21030, USA. · Takeda Pharmaceuticals, One Takeda Parkway, Deerfield, IL, 60015, USA. · Birmingham VA Medical Center, 700 S. 19th Street, Birmingham, AL, 35233, USA. · University of Alabama at Birmingham, Faculty Office Tower, Suite 820, 1720 2nd Avenue South, Birmingham, AL, 35294, USA. ·Arthritis Res Ther · Pubmed #29848361.

ABSTRACT: BACKGROUND: Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment (estimated glomerular filtrate rate ≥ 30 and < 60 ml/min). METHODS: This was an exploratory, 3-month, phase II, multicenter, placebo-controlled, double-blind proof-of-concept study. Patients (n = 189) were randomized 1:1:1:1:1 to receive placebo or febuxostat IR 40 mg, XR 40 mg, IR 80 mg, or XR 80 mg once daily. Endpoints included: proportion of patients with serum uric acid (sUA) < 5.0 mg/dl at month 3 (primary endpoint), proportion of patients with sUA < 6.0 mg/dl at month 3, and proportion of patients with ≥ 1 gout flare requiring treatment over 3 months. RESULTS: At month 3, all febuxostat treatment groups were associated with greater proportions of patients achieving sUA < 5.0 mg/dl (p < 0.05 vs placebo). A greater proportion of patients receiving XR 40 mg achieved sUA < 5.0 mg/dl versus those receiving IR 40 mg (p = 0.034); proportions were similar in the IR 80 mg and XR 80 mg groups. Higher proportions of febuxostat-treated patients achieved sUA < 6.0 mg/dl at month 3 (p < 0.05 vs placebo) and experienced ≥ 1 gout flare (significant for all comparisons, except XR 40 mg). Incidences of treatment-related adverse events were low across all treatment groups; the majority were mild or moderate with no apparent trends correlating with IR or XR doses. The most common treatment-emergent adverse event was hypertension. One death (unrelated to the study drug) was reported. CONCLUSIONS: These exploratory data demonstrate that febuxostat (XR and IR) formulations were effective and well tolerated in patients with gout and moderate renal impairment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02128490 Registered on 29 April 2014.

4 Clinical Trial Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study. 2017

Tausche, Anne-Kathrin / Alten, Rieke / Dalbeth, Nicola / Kopicko, Jeff / Fung, Maple / Adler, Scott / Bhakta, Nihar / Storgard, Chris / Baumgartner, Scott / Saag, Kenneth. ·Department of Rheumatology, Technical University Dresden, Dresden. · Department of Internal Medicine II, University Medicine Berlin, Berlin, Germany. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Global Medicines Development, Cardiovascular and Metabolic Diseases Clinical Development Unit, AstraZeneca Pharmaceuticals, Gaithersburg, MD. · Clinical Research and Development, Ardea Biosciences, Inc., San Diego, CA. · Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. ·Rheumatology (Oxford) · Pubmed #29029210.

ABSTRACT: Objective: To investigate the efficacy and safety of lesinurad, a selective uric acid reabsorption inhibitor, in a 6 month, phase 3 clinical trial and extension study. Methods: Patients with gout who cannot take a xanthine oxidase inhibitor (XOI) and have serum uric acid (sUA) ⩾6.5 mg/dl were randomized to receive oral lesinurad (400 mg daily) or placebo. The primary endpoint was the proportion of patients with sUA <6.0 mg/dl at month 6. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory data. Patients who completed the study were eligible for an open-label, uncontrolled extension study of lesinurad 400 mg monotherapy. Results: Patients (n = 214) were primarily white males (mean age 54.4 years; gout duration 11.2 years). Significantly more patients achieved the primary endpoint with lesinurad than placebo (29.9 vs 1.9%; P < 0.0001). Overall TEAE rates were higher with lesinurad (77.6 vs 65.4%); renal-related TEAEs (17.8%), renal-related serious TEAEs (4.7%) and serum creatinine elevations (1.5 times baseline, 24.3%) occurred only with lesinurad. A total of 143 patients (65 lesinurad, 78 placebo) enrolled in the extension study. Treatment with lesinurad 400 mg resulted in rapid and sustained sUA lowering that persisted for up to 18 months before the study was terminated prematurely. No new safety findings were observed in the extension. Conclusion: In patients with gout and intolerance/contraindication to XOIs, lesinurad 400 mg monotherapy demonstrated superior sUA lowering compared with placebo, with sustained effects for up to 18 months. Due to a high incidence of serum creatinine elevations and renal-related adverse events, including serious adverse events with lesinurad 400 mg, lesinurad should not be used as monotherapy. Trial registration: ClinicalTrials.gov (http://clinincaltrials.gov), NCT01508702.

5 Clinical Trial Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study. 2017

Dalbeth, Nicola / Saag, Kenneth G / Palmer, William E / Choi, Hyon K / Hunt, Barbara / MacDonald, Patricia A / Thienel, Ulrich / Gunawardhana, Lhanoo. ·University of Auckland, Auckland, New Zealand. · University of Alabama at Birmingham. · Massachusetts General Hospital, Harvard Medical School, Boston. · Takeda Development Center Americas, Deerfield, Illinois. · RRD International, Rockville, Maryland. ·Arthritis Rheumatol · Pubmed #28975718.

ABSTRACT: OBJECTIVE: To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). METHODS: In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. RESULTS: Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. CONCLUSION: Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout.

6 Clinical Trial Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study. 2012

Schumacher, H Ralph / Evans, Robert R / Saag, Kenneth G / Clower, James / Jennings, William / Weinstein, Steven P / Yancopoulos, George D / Wang, Jian / Terkeltaub, Robert. ·VA Medical Center and University of Pennsylvania, PA 19104, USA. schumacr@mail.med.upenn.edu ·Arthritis Care Res (Hoboken) · Pubmed #22549879.

ABSTRACT: OBJECTIVE: To evaluate the efficacy and safety of the interleukin-1 inhibitor rilonacept (interleukin-1 Trap) for gout flare prevention during initiation of uric acid-lowering therapy (ULT). METHODS: In total, 241 adult patients with gout, ≥2 gout flares within the past year, and a serum urate level ≥7.5 mg/dl were initiated on allopurinol 300 mg daily and randomly allocated in a 1:1:1 ratio to receive 16 once-weekly subcutaneous injections of placebo, rilonacept 80 mg, or rilonacept 160 mg, with a double (loading) dose on day 1. Allopurinol was titrated to achieve a serum urate level of <6.0 mg/dl. The study was powered for the primary efficacy end point, the number of gout flares per patient through week 16. RESULTS: More patients in the rilonacept groups (80.0% in the rilonacept 80 mg group, 86.4% in the rilonacept 160 mg group) completed the study than in the placebo group (72.5%; P < 0.05 for the rilonacept 160 mg group versus the placebo group). Over 16 weeks, the mean number of gout flares per patient was significantly reduced by rilonacept treatment (placebo: 1.06, rilonacept 80 mg: 0.29 [P < 0.001], rilonacept 160 mg: 0.21 [P < 0.001]). Significantly lower proportions of patients reported ≥1 gout flares with rilonacept 80 mg (18.8%) and rilonacept 160 mg (16.3%) relative to placebo (46.8%; P < 0.001 for both). Except for injection site reactions (1.3% in the placebo group versus 8.8% in the rilonacept 80 mg group [P = 0.0635, post hoc analysis] and 19.8% in the rilonacept 160 mg group [P = 0.0001, post hoc analysis]), the incidence of adverse events was generally balanced among the treatment groups. CONCLUSION: Rilonacept markedly reduced the occurrence of gout flares associated with the initiation of ULT. The efficacy and safety profile suggests that rilonacept may have the potential to improve long-term disease control for some patients by improving adherence to ULT by reducing flares during the first months after ULT initiation.

7 Article Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. 2018

White, William B / Saag, Kenneth G / Becker, Michael A / Borer, Jeffrey S / Gorelick, Philip B / Whelton, Andrew / Hunt, Barbara / Castillo, Majin / Gunawardhana, Lhanoo / Anonymous1101370. ·From the University of Connecticut School of Medicine, Farmington (W.B.W.) · the University of Alabama, Birmingham (K.G.S.) · University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois · the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.) · Michigan State University College of Human Medicine, Grand Rapids (P.B.G.) · and Johns Hopkins University School of Medicine, Baltimore (A.W.). ·N Engl J Med · Pubmed #29527974.

ABSTRACT: BACKGROUND: Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease. METHODS: We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization). RESULTS: In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis. CONCLUSIONS: In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).

8 Article Brief Report: Validation of a Definition of Flare in Patients With Established Gout. 2018

Gaffo, Angelo L / Dalbeth, Nicola / Saag, Kenneth G / Singh, Jasvinder A / Rahn, Elizabeth J / Mudano, Amy S / Chen, Yi-Hsing / Lin, Ching-Tsai / Bourke, Sandra / Louthrenoo, Worawit / Vazquez-Mellado, Janitzia / Hernández-Llinas, Hansel / Neogi, Tuhina / Vargas-Santos, Ana Beatriz / da Rocha Castelar-Pinheiro, Geraldo / Amorim, Rodrigo B C / Uhlig, Till / Hammer, Hilde B / Eliseev, Maxim / Perez-Ruiz, Fernando / Cavagna, Lorenzo / McCarthy, Geraldine M / Stamp, Lisa K / Gerritsen, Martijn / Fana, Viktoria / Sivera, Francisca / Taylor, William. ·University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, Alabama. · University of Auckland, Auckland, New Zealand. · University of Alabama at Birmingham. · Taichung Veterans General Hospital, Taichung, Taiwan. · Chiang Mai University, Chiang Mai, Thailand. · Hospital General de Mexico, Mexico City, Mexico. · Boston University School of Medicine, Boston, Massachusetts. · Boston University School of Medicine, Boston, Massachusetts, and Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Diakonhjemmet Hospital, Oslo, Norway. · Research Institute of Rheumatology of Russia, Moscow, Russia. · University of the Basque Country, Cruces University Hospital, and Biocruces Health Research Institute, Vizcaya, Spain. · University and IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. · Mater Misericordiae University Hospital, Dublin, Ireland. · University of Otago, Christchurch, New Zealand. · Westfries Gasthuis, Hoorn, The Netherlands. · Rigshospitalet Glostrup, Copenhagen, Denmark. · Hospital General Universitario Elda, Elda, Spain. · University of Wellington, Wellington, New Zealand. ·Arthritis Rheumatol · Pubmed #29161469.

ABSTRACT: OBJECTIVE: To perform external validation of a provisional definition of disease flare in patients with gout. METHODS: Five hundred nine patients with gout were enrolled in a cross-sectional study during a routine clinical care visit at 17 international sites. Data were collected to classify patients as experiencing or not experiencing a gout flare, according to a provisional definition. A local expert rheumatologist performed the final independent adjudication of gout flare status. Sensitivity, specificity, predictive values, and receiver operating characteristic (ROC) curves were used to determine the diagnostic performance of gout flare definitions. RESULTS: The mean ± SD age of the patients was 57.5 ± 13.9 years, and 89% were male. The definition requiring fulfillment of at least 3 of 4 criteria (patient-defined gout flare, pain at rest score of >3 on a 0-10-point numerical rating scale, presence of at least 1 swollen joint, and presence of at least 1 warm joint) was 85% sensitive and 95% specific in confirming the presence of a gout flare, with an accuracy of 92%. The ROC area under the curve was 0.97. The definition based on a classification and regression tree algorithm (entry point, pain at rest score >3, followed by patient-defined flare "yes") was 73% sensitive and 96% specific. CONCLUSION: The definition of gout flare that requires fulfillment of at least 3 of 4 patient-reported criteria is now validated to be sensitive, specific, and accurate for gout flares, as demonstrated using an independent large international patient sample. The availability of a validated gout flare definition will improve the ascertainment of an important clinical outcome in studies of gout.

9 Article Management of Gout. 2017

Singh, Jasvinder A / Saag, Kenneth G. ·From University of Alabama at Birmingham, Birmingham, Alabama. ·Ann Intern Med · Pubmed #28586901.

ABSTRACT: -- No abstract --

10 Article Sex differences in gout characteristics: tailoring care for women and men. 2017

Harrold, Leslie R / Etzel, Carol J / Gibofsky, Allan / Kremer, Joel M / Pillinger, Michael H / Saag, Kenneth G / Schlesinger, Naomi / Terkeltaub, Robert / Cox, Vanessa / Greenberg, Jeffrey D. ·Department of Medicine and Orthopedics, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. leslie.harrold@umassmed.edu. · Corrona, LLC, Southborough, MA, USA. · Department of Epidemiology, UT MD Anderson Cancer Center, Houston, TX, USA. · Hospital for Special Surgery-Weill Medical College of Cornell University, New York, NY, USA. · Albany Medical College and The Center for Rheumatology, Albany, NY, USA. · NYU School of Medicine, New York, NY, USA. · University of Alabama at Birmingham, Birmingham, AL, USA. · Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. · VA Medical Center, UCSD, San Diego, CA, USA. ·BMC Musculoskelet Disord · Pubmed #28292303.

ABSTRACT: BACKGROUND: To characterize the differences between women and men with gout. METHODS: We analyzed a US national cohort of gout patients cared for by rheumatologists. RESULTS: Compared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p < 0.001) and had a greater burden of comorbid conditions (p < 0.001 for hypertension, diabetes, renal disease and obesity). Risk factors for gout differed with women more often taking diuretics (p < 0.001), while men more frequently had dietary triggers (p < 0.05). CONCLUSIONS: The profiles of women and men with gout are markedly different, suggesting a need to tailor treatment recommendations.

11 Article Treat-to-target (T2T) recommendations for gout. 2017

Kiltz, U / Smolen, J / Bardin, T / Cohen Solal, A / Dalbeth, N / Doherty, M / Engel, B / Flader, C / Kay, J / Matsuoka, M / Perez-Ruiz, F / da Rocha Castelar-Pinheiro, G / Saag, K / So, A / Vazquez Mellado, J / Weisman, M / Westhoff, T H / Yamanaka, H / Braun, J. ·Rheumazentrum Ruhrgebiet, and Ruhr University Bochum, Herne, Germany. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · Assisitance Publique Hôpitaux de Paris Rheumatology Department, Lariboisière Hospital, University Paris Diderot, Sorbonne Paris-Cité and INSERM, UMR 1132, Paris, France. · Research Medical Unit INSERM, Université Paris VII-Denis Diderot Assistance Publique-Hôpitaux de Paris, Service de Cardiologie, Hôpital Lariboisière, Paris, France. · University of Auckland and Auckland District Health Board, Auckland, New Zealand. · University of Nottingham, Nottingham, UK. · Medical Faculty, Institute of General Practice and Family Medicine, University Bonn, Bonn, Germany. · UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, Massachusetts, USA. · Carnegie Mellon University, Pittsburgh, Pennsylvania, USA. · Rheumatology Division, Hospital de Cruces, Baracaldo, Vizcaya, Spain. · Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil. · University of Alabama at Birmingham, Birmingham, Alabama, USA. · Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. · Servicio de Reumatología, Hospital General de México, México City, México. · Division of Rheumatology, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, USA. · Medical Department I, Marien Hospital Herne, Ruhr-University of Bochum, Herne, Germany. · Tokyo Women's Medical University, Tokyo, Japan. ·Ann Rheum Dis · Pubmed #27658678.

ABSTRACT: OBJECTIVES: The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. METHODS: A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. CONCLUSIONS: This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon.

12 Article Lesinurad Combined With Allopurinol: A Randomized, Double-Blind, Placebo-Controlled Study in Gout Patients With an Inadequate Response to Standard-of-Care Allopurinol (a US-Based Study). 2017

Saag, Kenneth G / Fitz-Patrick, David / Kopicko, Jeff / Fung, Maple / Bhakta, Nihar / Adler, Scott / Storgard, Chris / Baumgartner, Scott / Becker, Michael A. ·University of Alabama at Birmingham. · East-West Medical Research Institute, Honolulu, Hawaii. · Ardea Biosciences, San Diego, California. · AstraZeneca Pharmaceuticals, Gaithersburg, Maryland. · University of Chicago, Chicago, Illinois. ·Arthritis Rheumatol · Pubmed #27564409.

ABSTRACT: OBJECTIVE: Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor. The Combining Lesinurad with Allopurinol Standard of Care in Inadequate Responders (CLEAR 1) study, a 12-month, multicenter, randomized, double-blind, placebo-controlled phase III trial, was conducted to investigate daily lesinurad (200 mg or 400 mg orally) added to allopurinol versus placebo plus allopurinol in patients with serum urate (UA) levels above a target of <6.0 mg/dl. METHODS: Patients receiving ≥300 mg of allopurinol (≥200 mg in those with moderate renal impairment) who had serum UA levels ≥6.5 mg/dl at screening and ≥2 gout flares during the previous year were studied. The primary end point was the proportion of patients achieving a serum UA level of <6.0 mg/dl at month 6. Key secondary end points were the mean gout flare rate requiring treatment (months 7-12) and the proportions of patients with complete resolution of ≥1 target tophus (month 12). Safety assessments included adverse events and laboratory data. RESULTS: The study patients (n = 603) were predominantly male and had a mean ± SD age of 51.9 ± 11.3 years, a gout duration of 11.8 ± 9.4 years, a baseline serum UA level of 6.94 ± 1.27 mg/dl, and were receiving an allopurinol dosage of 306.6 ± 59.58 mg/day. Lesinurad at doses of 200 mg or 400 mg added to allopurinol therapy significantly increased the proportions of patients who achieved serum UA target levels by month 6 as compared with those receiving allopurinol alone (54.2%, 59.2%, and 27.9%, respectively, P < 0.0001). Lesinurad was not significantly superior to allopurinol alone in terms of the secondary end points: rates of gout flares and complete resolution of tophi. Lesinurad was generally well-tolerated; the safety profile of the 200-mg dose was comparable to that of allopurinol alone, except for higher incidences of predominantly reversible elevations of serum creatinine levels. CONCLUSION: Lesinurad added to allopurinol provided benefit as compared with allopurinol alone in reducing serum UA levels and represents a new treatment option for patients needing additional urate-lowering therapy.

13 Article Rationale and design of the randomized evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) Study. 2016

Coburn, Brian W / Cheetham, T Craig / Rashid, Nazia / Chang, John M / Levy, Gerald D / Kerimian, Artak / Low, Kimberly J / Redden, David T / Bridges, S Louis / Saag, Kenneth G / Curtis, Jeffrey R / Mikuls, Ted R. ·Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United States. · Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, United States. · Drug Information Services, Kaiser Permanente Southern California, Downey, CA, United States. · Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States. · Division of Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United States. · Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United States; Medicine, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States. Electronic address: tmikuls@unmc.edu. ·Contemp Clin Trials · Pubmed #27449546.

ABSTRACT: BACKGROUND: Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA<6.0mg/dl. However, this strategy is not routinely used. Here we present the study design rationale and development for a pharmacist-led intervention to promote sUA goal attainment. METHODS: To overcome barriers in achieving optimal outcomes, we planned and implemented the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) study. This is a large pragmatic cluster-randomized trial designed to assess a highly automated, pharmacist-led intervention to optimize allopurinol treatment in gout. Ambulatory clinics (n=101) from a large health system were randomized to deliver either the pharmacist-led intervention or usual care to gout patients over the age of 18years newly initiating allopurinol. All participants received educational materials and could opt-out of the study. For intervention sites, pharmacists conducted outreach primarily via an automated telephone interactive voice recognition system. The outreach, guided by a gout care algorithm developed for this study, systematically promoted adherence assessment, facilitated sUA testing, provided education, and adjusted allopurinol dosing. The primary study outcomes are achievement of sUA<6.0mg/dl and treatment adherence determined after one year. With follow-up ongoing, study results will be reported subsequently. CONCLUSION: Ambulatory care pharmacists and automated calling technology represent potentially important, underutilized resources for improving health outcomes for gout patients.

14 Article Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment. 2016

Saag, Kenneth G / Whelton, Andrew / Becker, Michael A / MacDonald, Patricia / Hunt, Barbara / Gunawardhana, Lhanoo. ·Birmingham VA Medical Center, Birmingham, Alabama, and University of Alabama at Birmingham. · Johns Hopkins University, Baltimore, Maryland. · University of Chicago Pritzker School of Medicine, Chicago, Illinois. · Takeda Pharmaceuticals, Deerfield, Illinois. ·Arthritis Rheumatol · Pubmed #26894653.

ABSTRACT: OBJECTIVE: Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ). METHODS: Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. RESULTS: At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. CONCLUSION: Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function.

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 / 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.

16 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.

17 Article Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system. 2015

Rashid, Nazia / Coburn, Brian W / Wu, Yi-Lin / Cheetham, T Craig / Curtis, Jeffrey R / Saag, Kenneth G / Mikuls, Ted R. ·From the Drug Information Services, Kaiser Permanente Southern California Region, Downey; Department of Research and Evaluation, Kaiser Permanente, Pasadena, California; University of Nebraska Medical Center, and the Division of Rheumatology, Omaha VA, Omaha, Nebraska; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.N. Rashid, PharmD, MS, Research Scientist, Drug Information Services, Kaiser Permanente; B.W. Coburn, BS, University of Nebraska Medical Center; Y-L. Wu, MS; T.C. Cheetham, PharmD, MS, Department of Research and Evaluation, Kaiser Permanente; J.R. Curtis, MD, MS, MPH; K.G. Saag, MD, MSc, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; T.R. Mikuls, MD, MSPH, Division of Rheumatology, Omaha VA and University of Nebraska Medical Center. ·J Rheumatol · Pubmed #25512479.

ABSTRACT: OBJECTIVE: To identify modifiable patient and provider factors associated with allopurinol adherence and the achievement of a serum urate acid (SUA) goal in gout. METHODS: We identified a retrospective cohort of patients with gout, newly treated with allopurinol. All patient data came from administrative datasets at a large integrated health delivery system. Patients were ≥ 18 years old at time of initial allopurinol dispensing, and had 12 months or more of membership and drug eligibility prior to the index date. Allopurinol adherence was defined as a proportion of days covered ≥ 0.80, evaluated during the first 12 months of observation after the initial dispensing. Multivariable logistic regression was used to examine factors associated with allopurinol nonadherence and attaining an SUA concentration < 6.0 mg/dl. RESULTS: We identified 13,341 patients with gout with incident allopurinol use (mean age 60 yrs, 78% men). Of these, 9581 patients (72%) had SUA measured both at baseline and during followup. Only 3078 patients (32%) attained an SUA target of < 6.0 mg/dl during followup. Potentially modifiable factors associated with treatment adherence and obtaining the SUA goal in the multivariable analysis included concomitant diuretic use, prescriber specialty, and allopurinol dosing practices. Adherent patients were 2.5-fold more likely than nonadherent patients to achieve an SUA < 6.0 mg/dl during observation. CONCLUSION: Among patients with gout initiating allopurinol in our study, 68% did not reach the SUA goal and 57% of patients were nonadherent. Modifiable factors, including allopurinol dose escalation, treatment adherence, rheumatology referral, and concomitant medication use, could be important factors to consider in efforts aimed at optimizing gout treatment outcomes.

18 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.

19 Article Gout-related health care utilization in US emergency departments, 2006 through 2008. 2013

Garg, Rohini / Sayles, Harlan R / Yu, Fang / Michaud, Kaleb / Singh, Jasvinder / Saag, Kenneth G / Mikuls, Ted R. ·Creighton University, Omaha, Nebraska. ·Arthritis Care Res (Hoboken) · Pubmed #22949176.

ABSTRACT: OBJECTIVE: To characterize gout-related emergency department (ED) utilization using a nationally representative sample and to examine factors associated with the frequency and charges of gout-related ED visits. METHODS: Using the National Emergency Department Sample data from 2006-2008, the weighted national frequency of gout visits was calculated along with the median ED charge and total national ED-related charges. Associations of several patient- and facility-level factors were examined with the occurrence of gout visits using multivariable logistic regression and with ED-related charges using multivariable linear regression. RESULTS: Gout was the primary indication for 168,410 ED visits in 2006, 171,743 visits in 2007, and 174,823 visits in 2008, accounting for ∼0.2% of all visits annually and generating ED charges of more than $128 million in 2006, $144 million in 2007, and $166 million in 2008. Age, male sex, household income <$39,000, private insurance, and hospital locations in nonmetropolitan areas and the southern US were associated with an increased propensity for ED utilization in gout. Higher ED-related charges for gout were associated with female sex, age, a higher number of coded diagnoses, and a metropolitan residence. CONCLUSION: Gout accounts for a substantial proportion of ED visits, leading to significant health care charges. Effective strategies to reduce gout burden in EDs could potentially benefit by targeting groups characterized by factors demonstrated to be related to a higher ED utilization in gout as identified by our study.

20 Article Mortality due to coronary heart disease and kidney disease among middle-aged and elderly men and women with gout in the Singapore Chinese Health Study. 2012

Teng, Gim Gee / Ang, Li-Wei / Saag, Kenneth G / Yu, Mimi C / Yuan, Jian-Min / Koh, Woon-Puay. ·University Medicine Cluster, Division of Rheumatology, National University Health System, Singapore. ·Ann Rheum Dis · Pubmed #22172492.

ABSTRACT: OBJECTIVES: Whether the link between gout and mortality is causal or confounded by lifestyle factors or comorbidities remains unclear. Studies in Asia are warranted due to the rapid modernisation of the locale and ageing of the population. METHODS: The association between gout and mortality was examined in a prospective cohort, the Singapore Chinese Health Study, comprising 63 257 Singapore Chinese individuals, aged 45-74 years during the enrolment period of 1993-8. All enrollees were interviewed in person on lifestyle factors, current diet and medical histories. All surviving cohort members were contacted by telephone during 1999-2004 to update selected exposure and medical histories (follow-up I interview), including the history of physician-diagnosed gout. Cause-specific mortality in the cohort was identified via record linkage with the nationwide death registry, up to 31 December 2009. RESULTS: Out of 52 322 participants in the follow-up I interview, 2117 (4.1%) self-reported a history of physician-diagnosed gout, with a mean age at diagnosis of 54.7 years. After a mean follow-up period of 8.1 years, there were 6660 deaths. Relative to non-gout subjects, subjects with gout had a higher risk of death (HR 1.18; 95% CI 1.06 to 1.32), and specifically from death due to coronary heart disease (CHD) (HR 1.38, 95% CI 1.10 to 1.73) and kidney disease (HR 5.81, 95% CI 3.61 to 9.37). All gout-mortality risk associations were present in both genders but the risk estimates appeared higher for women. CONCLUSION: Gout is an independent risk factor for mortality, and specifically for death due to CHD and kidney disease.

21 Article Developing a provisional definition of flare in patients with established gout. 2012

Gaffo, Angelo L / Schumacher, H Ralph / Saag, Kenneth G / Taylor, William J / Dinnella, Janet / Outman, Ryan / Chen, Lang / Dalbeth, Nicola / Sivera, Francisca / Vázquez-Mellado, Janitzia / Chou, Chung-Tei / Zeng, Xuejun / Perez-Ruiz, Fernando / Kowalski, Sergio C / Goldenstein-Schainberg, Claudia / Chen, Lan / Bardin, Thomas / Singh, Jasvinder A. ·Birmingham VA Medical Center and University of Alabama at Birmingham, AL, USA. ·Arthritis Rheum · Pubmed #22083456.

ABSTRACT: OBJECTIVE: Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. METHODS: Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. RESULTS: The mean ± SD age of the study participants was 56.2 ± 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (0-10 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). CONCLUSION: We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials.

22 Article Bringing it all together: a novel approach to the development of response criteria for chronic gout clinical trials. 2011

Taylor, William J / Singh, Jasvinder A / Saag, Kenneth G / Dalbeth, Nicola / MacDonald, Patricia A / Edwards, N Lawrence / Simon, Lee S / Stamp, Lisa K / Neogi, Tuhina / Gaffo, Angelo L / Khanna, Puja P / Becker, Michael A / Schumacher, H Ralph. ·Department of Medicine, University of Otago, Wellington, New Zealand. will.taylor@otago.ac.nz ·J Rheumatol · Pubmed #21724718.

ABSTRACT: OBJECTIVE: To review a novel approach for constructing composite response criteria for use in chronic gout clinical trials that implements a method of multicriteria decision-making. METHODS: Preliminary work with paper patient profiles led to a restricted set of core-set domains that were examined using 1000Minds™ by rheumatologists with an interest in gout, and (separately) by OMERACT registrants prior to OMERACT 10. These results and the 1000Minds approach were discussed during OMERACT 10 to help guide next steps in developing composite response criteria. RESULTS: There were differences in how individual indicators of response were weighted between gout experts and OMERACT registrants. Gout experts placed more weight upon changes in uric acid levels, whereas OMERACT registrants placed more weight upon reducing flares. Discussion highlighted the need for a "pain" domain to be included, for "worsening" to be an additional level within each indicator, for a group process to determine the decision-making within a 1000Minds exercise, and for the value of patient involvement. CONCLUSION: Although there was not unanimous support for the 1000Minds approach to inform the construction of composite response criteria, there is sufficient interest to justify ongoing development of this methodology and its application to real clinical trial data.

23 Article Toward a valid definition of gout flare: results of consensus exercises using Delphi methodology and cognitive mapping. 2009

Taylor, W J / Shewchuk, R / Saag, K G / Schumacher, H R / Singh, J A / Grainger, R / Edwards, N L / Bardin, T / Waltrip, R W / Simon, L S / Burgos-Vargas, R. ·University of Otago and Wellington Regional Rheumatology Unit, Wellington, New Zealand. will.taylor@otago.ac.nz ·Arthritis Rheum · Pubmed #19333981.

ABSTRACT: OBJECTIVE: To identify, in people known to have gout, the testable, key components of a standard definition of gout flare for use in clinical research. METHODS: Consensus methodology was used to identify key elements of a gout flare. Two Delphi exercises were conducted among different groups of rheumatologists. A cognitive mapping technique among 9 gout experts with hierarchical cluster analysis provided a framework to guide the panel discussion, which identified the final set of items that should be tested empirically. RESULTS: From the Delphi exercises, 21 items were presented to the expert panel. Cluster analysis and multidimensional scaling showed that these items clustered into 5 concepts (joint inflammation, severity of symptoms, stereotypical nature, pain, and gout archetype) distributed along 2 dimensions (objective to subjective features and general features to specific features of gout). Using this analysis, expert panel discussion generated a short list of potential features: joint swelling, joint tenderness, joint warmth, severity of pain, patient global assessment, time to maximum pain, time to complete resolution of pain, an acute-phase marker, and functional impact of the episode. CONCLUSION: A short list of features has been identified and now requires validation against a patient- and physician-defined gout flare in order to determine the best combination of features.

24 Minor Reply. 2017

Saag, Kenneth G. ·University of Alabama, Birmingham, AL. ·Arthritis Rheumatol · Pubmed #27992695.

ABSTRACT: -- No abstract --