Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Gout: HELP
Articles by Michael A. Becker
Based on 26 articles published since 2010
(Why 26 articles?)
||||

Between 2010 and 2020, M. A. Becker wrote the following 26 articles about Gout.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Urate transporters: transforming the face of hyperuricemia and gout. 2014

Becker, Michael A / Simkin, Peter A / Sorensen, Leif B. ·Professor Emeritus, The University of Chicago Pritzker School of Medicine, Chicago, IL; becker@medicine.bsd.uchicago.edu. · Professor Emeritus of Medicine, University of Washington School of Medicine, Seattle, WA; · Professor Emeritus, The University of Chicago Pritzker School of Medicine, Chicago, IL, USA. ·J Rheumatol · Pubmed #25179848.

ABSTRACT: -- No abstract --

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

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

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

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

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

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

4 Review Long-term management of gout: nonpharmacologic and pharmacologic therapies. 2014

Chaichian, Yashaar / Chohan, Saima / Becker, Michael A. ·Section of Rheumatology, The University of Chicago, 5841 South Maryland Avenue, MC 0930, Chicago, IL 60637, USA. · Section of Rheumatology, The University of Chicago, 5841 South Maryland Avenue, MC 0930, Chicago, IL 60637, USA. Electronic address: mbecker@medicine.bsd.uchicago.edu. ·Rheum Dis Clin North Am · Pubmed #24703352.

ABSTRACT: Gout is a common disorder with clinical signs and symptoms resulting from inflammatory responses to monosodium urate crystals deposited in tissues from extracellular fluids saturated for urate. Long-term management of gout focuses on nonpharmacologic and pharmacologic means to achieve and maintain serum urate levels in a subsaturating range. Despite a firm understanding of gout pathophysiology, means to achieve certain diagnosis, and a variety of effective therapies, treatment outcomes remain suboptimal. In this review, available nonpharmacologic and pharmacologic therapies for chronic gout are discussed and a framework is provided for successful achievement and maintenance of goal-range serum urate levels.

5 Review What do I need to know about gout? 2010

Becker, Michael A / Ruoff, Gary E. ·Department of Medicine, University of Chicago Medical Center, Chicago, IL, USA. ·J Fam Pract · Pubmed #20544070.

ABSTRACT: Many patients with gout present with an acute attack (flare) of gouty arthritis. In its early stages, gout is a chronic, often silent disorder punctuated by acute, extremely painful arthritic flares. Over time, untreated or insufficiently treated gout may progress, with more frequent flares and formation of urate crystal deposits (tophi) and associated chronic, deforming arthritis (gouty arthropathy). About 20% of patients with gout have urinary tract stones and can develop an interstitial urate nephropathy. Gout (also called urate crystal deposition disease) is characterized by reduced renal clearance or, less frequently, an overproduction of uric acid. When the serum urate acid (sUA) level persistently exceeds 6.8 mg/dL, extracellular fluids become saturated and hyperuricemia occurs. Hyperuricemia is also very common among adult men and postmenopausal women, most of whom remain asymptomatic with respect to gout throughout their lives. Nevertheless, hyperuricemia is the major risk factor for gout because it predisposes to urate crystal formation and deposition, particularly in and around joints and in other soft tissue structures. The symptoms and signs of gout result from acute and chronic inflammatory responses of the body to urate crystal deposits. Although any joint may be affected, the metatarsophalangeal (MTP) joint of the great toe (podagra) is the first joint affected in half of all cases. One major goal in managing gout is to treat the pain of acute flares aggressively with anti-inflammatory agents to reduce flare intensity and duration. In addition, most patients with gout eventually require long-term treatment with urate-lowering therapy (ULT) to reverse the chronic urate crystal deposition and to prevent recurrent flares that can cause permanent joint damage.

6 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.

7 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.

8 Clinical Trial An open-label, 6-month study of allopurinol safety in gout: The LASSO study. 2015

Becker, Michael A / Fitz-Patrick, David / Choi, Hyon K / Dalbeth, Nicola / Storgard, Chris / Cravets, Matt / Baumgartner, Scott. ·Department of Medicine, University of Chicago Medicine, MC0930, 5841 S Maryland Ave, Chicago, IL 60637. Electronic address: mbecker@medicine.bsd.uchicago.edu. · East-West Medical Research Institute, Honolulu, HI. · Harvard Medical School, Boston, MA; Gout and Crystal Arthropathy Center, Massachusetts General Hospital, Boston, MA. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Clinical Research and Development, Ardea Biosciences Inc., San Diego, CA. · Medical Affairs, Ardea Biosciences, Inc., San Diego, CA, USA. · Biostatistics, Ardea Biosciences, Inc., San Diego, CA, USA. ·Semin Arthritis Rheum · Pubmed #26190562.

ABSTRACT: OBJECTIVES: Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses > 300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses. METHODS: Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and ≥ 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA < 6.0mg/dL. The primary objective was evaluation of the safety of dose-titrated allopurinol by clinical and laboratory examinations at monthly visits. Secondary objectives included sUA-lowering efficacy and gout flare frequency. RESULTS: Of 1735 patients enrolled, 1732 received ≥ 1 allopurinol doses. The maximal daily allopurinol dose during study was < 300 mg in 14.4%, 300 mg in 65.4%, and > 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the < 300-, 300-, and > 300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred in laboratory values. sUA < 6.0mg/dL at month 6 was achieved by 35.9% of patients overall: 22.4%, 35.0%, and 48.3% in dosing categories < 300, 300, and > 300 mg, respectively. CONCLUSIONS: This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA.

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

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

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

10 Clinical Trial Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol. 2012

Chohan, Saima / Becker, Michael A / MacDonald, Patricia A / Chefo, Solomon / Jackson, Robert L. ·University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA. schohan@medicine.bsd.uchicago.edu ·Arthritis Care Res (Hoboken) · Pubmed #22052584.

ABSTRACT: OBJECTIVE: To compare the characteristics of female versus male gout patients and assess urate-lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout. METHODS: This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level ≥8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function). Baseline demographics and characteristics were summarized and compared between female and male subjects. Urate-lowering efficacy, which was defined as the proportion of subjects with sUA levels <6.0 mg/dl at final visit, was assessed for all subjects and, among women, according to baseline renal function. RESULTS: Female gout subjects (n = 226) were older with significantly higher rates of obesity and metabolic and cardiovascular comorbidities than their male counterparts. The percentage of female subjects with sUA levels <6.0 mg/dl at final visit was 0% in the placebo group, 54.3%, 85.1%, 81.0%, and 100.0% in the febuxostat 40 mg, 80 mg, 120 mg, and 240 mg groups, respectively, and 45.9% in the allopurinol group. Similar patterns of urate-lowering efficacy rates were observed when stratified by renal function. Among all the female subjects, febuxostat 80 mg was significantly more efficacious than allopurinol (P < 0.001). Rates of adverse events (AEs) were low. The most frequently reported AEs were upper respiratory tract infections, musculoskeletal/connective tissue disorders, and diarrhea. CONCLUSION: These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities.

11 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 .).

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 Summary of the 2015 Purine and Pyrimidine Society/Purine Metabolic Patients Association H. Anne Simmonds Memorial Lecture. 2016

Becker, Michael A. ·a Rheumatology Section, Department of Medicine , The University of Chicago Pritzker School of Medicine , Chicago , IL , USA. ·Nucleosides Nucleotides Nucleic Acids · Pubmed #27906633.

ABSTRACT: -- No abstract --

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

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

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

16 Article A revised estimate of the burden of illness of gout. 2013

Wertheimer, Albert / Morlock, Robert / Becker, Michael A. ·Department of Pharmacy Practice, Temple University, Philadelphia, Pennsylvania. · Ardea Biosciences, San Diego, California. · Department of Medicine, University of Chicago, Chicago, Illinois. ·Curr Ther Res Clin Exp · Pubmed #24465034.

ABSTRACT: BACKGROUND: Gout is a chronic, inflammatory arthritis characterized by painful and debilitating acute/episodic flares. Until recently, gout has been regarded as a minor medical problem, in part because the associated economic burden has not been appreciated. Previous literature on this subject focused on the costs associated with acute episodes of gout rather than on the long-term medical and economic implications of this chronic disorder. OBJECTIVE: Our aim was to estimate the current impact of gout in the United States with respect to disability and economic costs. METHODS: THE FOLLOWING DATA SOURCES WERE USED: published data on the incremental economic burden of gout; statistics from the US Census Bureau and the US Bureau of Labor Statistics; and recent epidemiological and clinical literature concerning the course, treatment, and outcomes of the disease. Disability is expressed as days of lost productivity. Charges for gout-related treatments were used as direct cost inputs. RESULTS: Gout affects an estimated 8 million Americans, among whom those working have an average of almost 5 more absence days annually than workers without gout. On average, the incremental annual cost of care for a gout patient is estimated at >$3000 compared with a nongouty individual. Even though comorbidities common in gout patients account for a portion of this increased economic burden, the total annual cost attributable to gout patients in the United States is likely in the tens of billions of dollars and comparable to those of other major chronic disorders, such as migraine and Parkinson's disease. CONCLUSIONS: The economic burden of gout is most readily assessable in patients whose acute arthritic flares result in emergency department visits, bedridden days, and episodic loss of productivity. Chronic progression of the disease can also result in long-term impairment of function and health-related quality of life, but the contribution of chronic gout to the economic burden is more difficult to quantitate because gout is frequently associated with serious cardiovascular, metabolic, and renal comorbidities. Recent demonstration that successful gout management can reverse functional deficits in many chronic gout patients, however, supports the views that chronic gout contributes substantially to the medical and thus economic costs of these patients and that early and aggressive efforts to improve gout outcomes are likely to reduce the associated economic burden.

17 Article Diabetes and gout: efficacy and safety of febuxostat and allopurinol. 2013

Becker, M A / MacDonald, P A / Hunt, B J / Jackson, R L. ·Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA. ·Diabetes Obes Metab · Pubmed #23683134.

ABSTRACT: AIM: Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents. METHODS: Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [baseline serum urate levels (sUA) ≥8.0 mg/dl] enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl. Safety was monitored throughout the trial. RESULTS: Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (body mass index >30 kg/m²) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p < 0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events. CONCLUSIONS: Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses.

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

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

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

19 Article Treating hyperuricemia of gout: safety and efficacy of febuxostat and allopurinol in older versus younger subjects. 2011

Becker, Michael A / MacDonald, Patricia A / Hunt, Barbara / Gunawardhana, Lhanoo. ·University of Chicago, Pritzker School of Medicine, University of Chicago Medical Center, Chicago, Illinois 60637, USA. mbecker@medicine.bsd.uchicago.edu ·Nucleosides Nucleotides Nucleic Acids · Pubmed #22132950.

ABSTRACT: Despite an increasing incidence of gout in older age patients with multiple metabolic and cardiovascular comorbidities, there are limited data addressing whether currently available urate-lowering therapy is comparably effective and safe in older (≥65 years of age) versus younger (<65 years of age) patients. In this secondary analysis of data from the CONFIRMS trial, we found that among 374 older subjects, urate-lowering therapy with approved doses of febuxostat or commonly prescribed doses of allopurinol was at least comparable to that in 1894 younger subjects and was well tolerated despite high rates of renal impairment and cardiovascular comorbidities in the older subjects.

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

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

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

21 Article 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.

22 Article Serum urate in chronic gout--will it be the first validated soluble biomarker in rheumatology? 2011

Stamp, Lisa K / Khanna, Puja P / Dalbeth, Nicola / Boers, Maarten / Maksymowych, Walter P / Schumacher, H Ralph / Becker, Michael A / MacDonald, Patricia A / Edwards, N Lawrence / Singh, Jasvinder A / Simon, Lee S / McQueen, Fiona M / Neogi, Tuhina / Gaffo, Angelo L / Strand, Vibeke / Taylor, William J. ·Department of Medicine, University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz ·J Rheumatol · Pubmed #21724717.

ABSTRACT: OBJECTIVE: To summarize evidence for and endorsement of serum urate (SU) as having fulfilled the OMERACT filter as a soluble biomarker in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). METHODS: Data were presented to support the use of SU as a soluble biomarker in chronic gout and specifically the ability to utilize it to predict future patient-reported outcomes. RESULTS: SU was accepted as having fulfilled the OMERACT filter by 78% of voters. However, consensus was not obtained regarding its use as a soluble biomarker in chronic gout. Although the majority of the criteria for a soluble biomarker were fulfilled, the key criterion of association of the biomarker with outcomes was not agreed upon. It was agreed that the appropriate choice of endpoint must be linked to its clinical importance to the individual with the disorder and its temporal relationship to the intervention. Appropriate outcomes in chronic gout may therefore include gout flares, reduction in tophi, and patient-reported outcomes. CONCLUSION: SU is a critical outcome measure. It has the potential to fulfil criteria for a soluble biomarker. Further analyses of existing data from randomized controlled trials will be required to determine whether SU can predict future important outcomes, in particular disability.

23 Article Tophus measurement as an outcome measure for clinical trials of chronic gout: progress and research priorities. 2011

Dalbeth, Nicola / McQueen, Fiona M / Singh, Jasvinder A / MacDonald, Patricia A / Edwards, N Lawrence / Schumacher, H Ralph / Simon, Lee S / Stamp, Lisa K / Neogi, Tuhina / Gaffo, Angelo L / Khanna, Puja P / Becker, Michael A / Taylor, William J. ·Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz ·J Rheumatol · Pubmed #21724716.

ABSTRACT: Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed upon method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to more complex advanced imaging methods. This article summarizes methods of tophus measurement and discusses their properties. Physical measurement using Vernier calipers meets most aspects of the Outcome Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change, is needed to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient-reported outcome measure of tophus burden is also highlighted.

24 Article Patient-reported outcomes in chronic gout: a report from OMERACT 10. 2011

Singh, Jasvinder A / Taylor, Will J / Simon, Lee S / Khanna, Puja P / Stamp, Lisa K / McQueen, Fiona M / Neogi, Tuhina / Gaffo, Angelo L / Becker, Michael A / MacDonald, Patricia A / Dabbous, Omar / Strand, Vibeke / Dalbeth, Nicola D / Aletaha, Daniel / Edwards, N Lawrence / Schumacher, H Ralph. ·Medicine Service, Birmingham Veterans Affairs (VA) Medical Center and Division of Rheumatology, Department of Medicine, University of Alabama, Birmingham, AL 35294, USA. jasvinder.md@gmail.com ·J Rheumatol · Pubmed #21724715.

ABSTRACT: OBJECTIVE: To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). METHODS: During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9. RESULTS: One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure. CONCLUSION: With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group.

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

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

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

Next