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Gout: HELP
Articles by Kenneth G. Saag
Based on 32 articles published since 2010
(Why 32 articles?)
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Between 2010 and 2020, K. Saag wrote the following 32 articles about Gout.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Vascular Consequences of Hyperuricemia and Hypouricemia. 2019

Albert, Daniel / Scudder, Paige N / Bagley, Pamela / Saag, Kenneth G. ·The Dartmouth Institute, Geisel School of Medicine, Dartmouth-Hitchcock Medical Center, 1 Rope Ferry Road, Hanover, NH 03755, USA. Electronic address: Daniel.A.Albert@Hitchcock.org. · Biomedical Libraries, Dartmouth College, Hanover, NH, USA. · Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama Birmingham, 1670 University Boulevard, Birmingham, AL 35233, USA. ·Rheum Dis Clin North Am · Pubmed #31277755.

ABSTRACT: There are more than 10,000 articles in the literature published since 1999 that appear in a search of hyperuricemia and hypouricemia for vascular events. Systematic reviews were reviewed for this time frame, numbering approximately 300 articles in addition to more than 400 reports of randomized clinical trials published since 2017. In summary, the epidemiologic associations of hyperuricemia and hypouricemia with vascular disease are confounded by comorbid conditions. The interventional data are suggestive of a relationship of gout and vascular disease and to a lesser extent hyperuricemia and hypertension; however, more interventional studies are necessary to confirm these relationships.

2 Review Is there a role for cherries in the management of gout? 2019

Collins, Marcum W / Saag, Kenneth G / Singh, Jasvinder A. ·UAB Hospital, 1720 2nd Avenue South, FOT 839, Birmingham, AL 35294, USA. · University of Alabama at Birmingham, Birmingham, AL, USA. · Birmingham VA Med Center, Birmingham, USA. ·Ther Adv Musculoskelet Dis · Pubmed #31205513.

ABSTRACT: Despite the availability of effective urate-lowering therapy (ULT) and anti-inflammatory drugs for the treatment of gout, there is considerable interest in novel treatment approaches. Patients with gout often have a multitude of comorbidities, leading to concern over drug-drug interactions and medication adverse events. The cherry is a small nutrient-rich fruit that has garnered a great deal of attention in recent years as a nonpharmacologic option for the treatment of a multitude of disease manifestations. Perhaps a quarter of patients with gout try cherries or cherry products to treat their gout, which have antioxidant and anti-inflammatory (IL-6, TNF-α, IL-1β, IL-8, COX-I and -II) properties, hypouricemic effects, and the ability to downregulate NFkB-mediated osteoclastogenesis. Based on these properties, cherries may reduce both the acute and chronic inflammation associated with recurrent gout flares and its chronic destructive arthropathy. In this review, we explore the potential benefits of cherries and cherry products as a nonpharmacologic option for the treatment of gout.

3 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.

4 Clinical Trial Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study. 2019

Saag, Kenneth G / Becker, Michael A / Whelton, Andrew / Hunt, Barbara / Castillo, Majin / Kisfalvi, Krisztina / Gunawardhana, Lhanoo. ·Birmingham VA Medical Center, Birmingham, Alabama, and University of Alabama at Birmingham. · University of Chicago Pritzker School of Medicine, Chicago, Illinois. · Johns Hopkins University, Baltimore, Maryland. · Takeda Pharmaceuticals, Deerfield, Illinois. ·Arthritis Rheumatol · Pubmed #30073793.

ABSTRACT: OBJECTIVE: To assess the efficacy and safety of febuxostat extended release (XR) and immediate release (IR) in patients with gout and normal or impaired renal function. METHODS: This was a 3-month, phase III, multicenter, double-blind, placebo-controlled study. Patients (n = 1,790) with a history of gout and normal or impaired (mild-to-severe) renal function were randomized to receive placebo, febuxostat IR 40 or 80 mg, or febuxostat XR 40 or 80 mg once daily (1:1:1:1:1 ratio). End points included proportions of patients with a serum urate (UA) level of <5.0 mg/dl at month 3 (primary end point), a serum UA level of <6.0 mg/dl at month 3, and ≥1 gout flare requiring treatment over 3 months (secondary end points). RESULTS: Both febuxostat formulations led to significantly greater proportions of patients achieving a serum UA level of <5.0 mg/dl or <6.0 mg/dl at month 3 (P < 0.001 for all comparisons versus placebo). Equivalent doses of febuxostat XR and IR had similar treatment effects on serum UA level end points; however, a significantly greater proportion of patients achieved a serum UA level of <5.0 mg/dl with XR 40 mg versus IR 40 mg. Similar proportions of patients experienced ≥1 gout flare across treatment groups. Rates of treatment-emergent adverse events were low and evenly distributed between treatment arms. A preplanned subgroup analysis demonstrated that febuxostat formulations were well tolerated and generally effective on serum UA level end points (versus placebo) across all renal function subgroups. CONCLUSION: Both formulations of febuxostat (XR and IR) were well tolerated and effective in patients with gout and normal or impaired renal function, including patients with severe renal impairment.

5 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.

6 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.

7 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.

8 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.

9 Article Gout is associated with an increased risk for incident heart failure among older adults: the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study. 2020

Colantonio, Lisandro D / Saag, Kenneth G / Singh, Jasvinder A / Chen, Ligong / Reynolds, Richard J / Gaffo, Angelo / Plante, Timothy B / Curtis, Jeffrey R / Bridges, S Louis / Levitan, Emily B / Chaudhary, Ninad S / Howard, George / Safford, Monika M / Muntner, Paul / Irvin, Marguerite Ryan. ·Department of Epidemiology, University of Alabama at Birmingham, 1720 2nd Ave South, RPHB 527C, Birmingham, AL, 35294-0013, USA. lcolantonio@uab.edu. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Epidemiology, University of Alabama at Birmingham, 1720 2nd Ave South, RPHB 527C, Birmingham, AL, 35294-0013, USA. · Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA. · Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA. · Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Medicine, Weill Cornell Medical College, New York, NY, USA. ·Arthritis Res Ther · Pubmed #32299504.

ABSTRACT: BACKGROUND: Gout has been associated with a higher risk for coronary heart disease (CHD) and stroke in some prior studies. Few studies have assessed the association of gout with incident heart failure (HF). METHODS: We analyzed data from 5713 black and white men and women ≥ 65.5 years of age in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study who had Medicare coverage without a history of HF, CHD, or stroke at baseline between 2003 and 2007. Gout was defined by ≥ 1 hospitalization or ≥ 2 outpatient visits with a diagnosis code for gout in Medicare claims prior to each participant's baseline study examination. REGARDS study participants were followed for HF hospitalization, CHD, stroke, and all-cause mortality as separate outcomes through December 31, 2016. Analyses were replicated in a random sample of 839,059 patients ≥ 65.5 years of age with Medicare coverage between January 1, 2008, and June 30, 2015, who were followed through December 31, 2017. RESULTS: Among REGARDS study participants included in the current analysis, the mean age at baseline was 72.6 years, 44.9% were men, 31.4% were black, and 3.3% had gout. Over a median follow-up of 10.0 years, incidence rates per 1000 person-years among participants with and without gout were 13.1 and 4.4 for HF hospitalization, 16.0 and 9.3 for CHD, 9.3 and 8.2 for stroke, and 55.0 and 37.1 for all-cause mortality, respectively. After multivariable adjustment for sociodemographic variables and cardiovascular risk factors, hazard ratios (95% CI) comparing participants with versus without gout were 1.97 (1.22, 3.19) for HF hospitalization, 1.21 (0.79, 1.84) for CHD, 0.83 (0.48, 1.43) for stroke, and 1.08 (0.86, 1.35) for all-cause mortality. The multivariable-adjusted hazard ratio for HF hospitalization with reduced and preserved left ventricular ejection fraction among participants with versus without gout was 1.77 (95% CI 0.83, 3.79) and 2.32 (95% CI 1.12, 4.79), respectively. The multivariable-adjusted hazard ratio for heart failure hospitalization associated with gout among the 839,059 Medicare beneficiaries was 1.32 (95% CI 1.25, 1.39). CONCLUSION: Among older adults, gout was associated with an increased risk for incident HF but not for incident CHD, incident stroke, or all-cause mortality.

10 Article Factors Influencing the Effectiveness of Allopurinol in Achieving and Sustaining Target Serum Urate in a US Veterans Affairs Gout Cohort. 2020

Singh, Jasvinder A / Yang, Shuo / Saag, Kenneth G. ·From the Birmingham Veterans Affairs Medical Center; Department of Medicine at the School of Medicine, and Department of Epidemiology at the School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA. Jasvinder.md@gmail.com. · J.A. Singh, MBBS, MPH, Birmingham Veterans Affairs Medical Center, and Department of Medicine at the School of Medicine, and Department of Epidemiology at the School of Public Health, University of Alabama at Birmingham; S. Yang, MS, Department of Epidemiology at the School of Public Health, University of Alabama at Birmingham; K.G. Saag, MD, MSc, Department of Medicine at the School of Medicine, University of Alabama at Birmingham. Jasvinder.md@gmail.com. · From the Birmingham Veterans Affairs Medical Center; Department of Medicine at the School of Medicine, and Department of Epidemiology at the School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA. · J.A. Singh, MBBS, MPH, Birmingham Veterans Affairs Medical Center, and Department of Medicine at the School of Medicine, and Department of Epidemiology at the School of Public Health, University of Alabama at Birmingham; S. Yang, MS, Department of Epidemiology at the School of Public Health, University of Alabama at Birmingham; K.G. Saag, MD, MSc, Department of Medicine at the School of Medicine, University of Alabama at Birmingham. ·J Rheumatol · Pubmed #31416925.

ABSTRACT: OBJECTIVE: To assess factors associated with the ability to achieve and maintain target serum urate (SU) with allopurinol in patients with gout. METHODS: We used US Veterans Affairs (VA) databases from 2002-2012. Eligible patients had ≥ 1 inpatient or ≥ 2 outpatient visits with a diagnostic code for gout, filled a new index allopurinol prescription, had at least 1 posttreatment SU level measured, and met the 12-month observability rule. Treatment successes were defined as the achievement of postindex SU < 6 mg/dl (success 1) and postindex SU < 6 mg/dl that was sustained (success 2). RESULTS: Of the 198,839 unique patients with allopurinol use, 41,153 unique patients (with 47,072 episodes) and 17,402 unique patients (with 18,323 episodes) were eligible for analyses for success 1 and success 2; 42% each achieved (success 1) or achieved and maintained postindex SU < 6 mg/dl (success 2). In multivariable-adjusted models, factors associated with significantly higher odds of both outcomes were older age, normal body mass index, Deyo-Charlson index score of 0, rheumatologist as the main provider rather than non-rheumatologist, midwestern US location for the healthcare facility, a lower hospital bed size, military service connection for medical conditions of 50% or more (a measure of healthcare access priority), longer distance to the nearest VA facility, and lower preindex SU. CONCLUSION: We identified novel factors associated with maintaining SU < 6 mg/dl based on a theoretical model. Several potentially modifiable factors can be targeted by individual/provider/systems interventions for improving successful achievement and maintenance of target SU in patients with gout.

11 Article Comparison of an interactive voice response system and smartphone application in the identification of gout flares. 2019

Elmagboul, Nada / Coburn, Brian W / Foster, Jeffrey / Mudano, Amy / Melnick, Joshua / Bergman, Debra / Yang, Shuo / Redden, David / Chen, Lang / Filby, Cooper / Curtis, Jeffrey R / Mikuls, Ted R / Saag, Kenneth G. ·University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL, 35294, USA. · University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. · University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL, 35294, USA. ksaag@uabmc.edu. ·Arthritis Res Ther · Pubmed #31255174.

ABSTRACT: OBJECTIVE: To examine the feasibility, preference, and satisfaction of an interactive voice response (IVR) system versus a customized smartphone application (StudyBuddy) to capture gout flares METHODS: In this 24-week prospective, randomized, crossover, open-label pilot study, 44 gout patients were randomized to IVR vs. StudyBuddy and were crossed over to the other technology after 12 weeks. Flares were reported via weekly (and later daily) scheduled StudyBuddy or IVR queries. Feasibility was ascertained via response rate to scheduled queries. At 12 and 24 weeks, participants completed preference/satisfaction surveys. Preference and satisfaction were assessed using dichotomous or ordinal questions. Sensitivity was assessed by the frequency of flare reporting with each approach. RESULTS: Thirty-eight of 44 participants completed the study. Among completers, feasibility was similar for IVR (81%) and StudyBuddy (80%). Conversely, most (74%) preferred StudyBuddy. Measures of satisfaction (ease of use, preference over in-person clinic visits, and willingness for future use) were similar between the IVR and StudyBuddy; however, more participants deemed the StudyBuddy as convenient (95% vs. 73%, P = 0.01) and less disruptive (97% vs. 82%, P = 0.03). Although the per patient number of weeks in flare was not significantly different (mean 3.4 vs. 2.6 weeks/patient, P = 0.15), the StudyBuddy captured more of the total flare weeks (35%) than IVR (27%, P = 0.02). CONCLUSION: A smartphone application and IVR demonstrated similar feasibility but overall sensitivity to capture gout flares and participant preference were greater for the smartphone application. Participant preference for the smartphone application appeared to relate to perceptions of greater convenience and lower disruption. TRIAL REGISTRATION: NCT, NCT02855437 . Registered 4 August 2016.

12 Article Adherence and Outcomes with Urate-Lowering Therapy: A Site-Randomized Trial. 2019

Mikuls, Ted R / Cheetham, T Craig / Levy, Gerald D / Rashid, Nazia / Kerimian, Artak / Low, Kimberly J / Coburn, Brian W / Redden, David T / Saag, Kenneth G / Foster, P Jeffrey / Chen, Lang / Curtis, Jeffrey R. ·Division of Rheumatology, University of Nebraska Medical Center and Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Neb. Electronic address: tmikuls@unmc.edu. · Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, Calif; Western University of Health Sciences, College of Pharmacy, Pomona, Calif. · Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, Calif. · Drug Information Services, Kaiser Permanente Southern California, Downey, Calif. · Division of Rheumatology, University of Nebraska Medical Center and Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Neb. · Department of Biostatistics, University of Alabama at Birmingham. · Division of Rheumatology, University of Alabama at Birmingham. ·Am J Med · Pubmed #30503879.

ABSTRACT: PURPOSE: The purpose of this study was to test a pharmacist-led intervention to improve gout treatment adherence and outcomes. METHODS: We conducted a site-randomized trial (n=1463 patients) comparing a 1-year, pharmacist-led intervention to usual care in patients with gout initiating allopurinol. The intervention was delivered primarily through automated telephone technology. Co-primary outcomes were the proportion of patients adherent (proportion of days covered ≥0.8) and achieving a serum urate <6.0 mg/dl at 1 year. Outcomes were reassessed at year 2. RESULTS: Patients who underwent intervention were more likely than patients of usual care to be adherent (50% vs 37%; odds ratio [OR] 1.68; 95% confidence interval [CI] 1.30, 2.17) and reach serum urate goal (30% vs 15%; OR 2.37; 95% CI 1.83, 3.05). In the second year (1 year after the intervention ended), differences were attenuated, remaining significant for urate goal but not for adherence. The intervention was associated with a 6%-16% lower gout flare rate during year 2, but the differences did not reach statistical significance. CONCLUSIONS: A pharmacist-led intervention incorporating automated telephone technology improved adherence and serum urate goal in patients with gout initiating allopurinol. Although this light-touch, low-tech intervention was efficacious, additional efforts are needed to enhance patient engagement in gout management and ultimately to improve outcomes.

13 Article Integrated safety studies of the urate reabsorption inhibitor lesinurad in treatment of gout. 2019

Terkeltaub, Robert / Saag, Kenneth G / Goldfarb, David S / Baumgartner, Scott / Schechter, Bruce M / Valiyil, Ritu / Jalal, Diana / Pillinger, Michael / White, William B. ·VA Healthcare System, University of California, San Diego, CA, USA. · Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Medicine, New York University School of Medicine, New York, NY, USA. · Clinical Research, Ironwood Pharmaceuticals, Inc., Cambridge, MA, USA. · Department of Medicine, University of Iowa, Iowa City, IA, USA. · Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA. ·Rheumatology (Oxford) · Pubmed #30124941.

ABSTRACT: Objective: Lesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy. Methods: Safety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years). Results: In the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals. Conclusion: At the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.

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

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

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

15 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 / Anonymous4290939. ·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 .).

16 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.

17 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 --

18 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.

19 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.

20 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.

21 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.

22 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.

23 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.

24 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.

25 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.

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