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Gout: HELP
Articles from Chicago
Based on 36 articles published since 2008
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These are the 36 published articles about Gout that originated from Chicago during 2008-2019.
 
+ 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 Editorial Transient receptor potential melastatin 2: a novel target for treatment of gout. 2013

Zhong, Zhenyu / Zhai, Yougang / Qiao, Liang. ·Loyola University Chicago, Stritch School of Medicine, Department of Microbiology and Immunology , 2610 South First Ave, Maywood, IL 60153 , USA lqiao@lumc.edu. ·Expert Opin Ther Targets · Pubmed #24004350.

ABSTRACT: Gout is an ancient autoinflammatory disease that affects millions of people worldwide. It is characterized by unbearable recurrent pain due to the massive local inflammation caused by the metabolic product, monosodium urate crystals. Although conventional therapies for gout can reduce the pain in patients, the severe undesirable side effects require the urgent need for novel therapies that can more specifically target gout-associated inflammatory pathways. Recent scientific advance on the mechanistic study of gout-associated inflammation is discussed and the potential of targeting the transient receptor potential melastatin 2 is highlighted as a novel therapeutic approach for the treatment of gout.

3 Review Toxic Epidermal Necrolysis with Gastrointestinal Involvement: A Case Report and Review of the Literature. 2017

Brown, Craig S / Defazio, Jennifer R / An, Gary / O'Connor, Annemarie / Whitcomb, Emma / Hart, John / Gottlieb, Lawrence J. ·From the *Department of Surgery, and †Department of Pathology, University of Chicago Medicine, Illinois. ·J Burn Care Res · Pubmed #27058583.

ABSTRACT: Gastrointestinal involvement is a rare complication of toxic epidermal necrolysis syndrome (TENS) that results in sloughing of the intestinal epithelium. Prior case reports have noted the potential susceptibility of the entire gastrointestinal tract, from oropharynx and esophagus to sigmoid colon and rectum. Given its infrequency, the effect of gastrointestinal involvement on the treatment and prognosis of TENS is poorly understood. Here, the authors report a case of gastrointestinal symptoms in a patient diagnosed with toxic epidermal necrolysis, likely representing gastrointestinal involvement. In addition, the authors describe the histopathologic and endoscopic characteristics of the involved mucosa, clinical course, and present a review of the literature of this rare but potentially impactful complication of TENS.

4 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.

5 Review Safety of allopurinol compared with other urate-lowering drugs in patients with gout: a systematic review and meta-analysis. 2015

Castrejon, Isabel / Toledano, Esther / Rosario, María Piedad / Loza, Estíbaliz / Pérez-Ruiz, Fernando / Carmona, Loreto. ·Division of Rheumatology, Rush University Medical Center, 1611 West Harrison Street, Suite 510, Chicago, IL, 60612, USA, isabelcastrejonf@gmail.com. ·Rheumatol Int · Pubmed #25519877.

ABSTRACT: SELECTION CRITERIA: (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis. PRIMARY OUTCOMES: rate of adverse events and death. The quality was assessed with the Jadad's scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40-240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6-85) and febuxostat (range 41.8-80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.

6 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.

7 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.

8 Review Managing new-onset gout in pediatric renal transplant recipients: when, how, to what extent. 2013

Assadi, Farahnak. ·Section of Nephrology, Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA. fassadi@rush.edu ·J Nephrol · Pubmed #22941874.

ABSTRACT: Hyperuricemia and gout are common among adult renal transplant recipients, but it is rarely reported following pediatric renal transplantations. Treating gout in pediatric kidney transplant recipients presents clinical challenges to the management of both immunosuppressive regimen and hyperuricemia for their effects on serum uric acid levels, renal function and drug interactions. Most renal transplant recipients have a relative impairment of renal clearance of urate due to abnormalities in renal transport, explaining the association of hyperuricemia and decreased glomerular filtration rate. Risk factors for the development of gout include impaired renal function, hypertension, heart failure and diabetes mellitus. Calcineurin inhibitors, particularly cyclosporine, are the most important risk factor for gout in transplant recipients and should not be used in pediatric renal transplant recipients. Diuretic therapy increases the risk of gout by causing extracellular volume contraction with consequent enhancement of proximal tubular reabsorption. Corticosteroids are increasingly replacing nonsteroidal antiinflammatory drugs and colchicine for the treatment of acute gout flares because they have little effect on kidney function. Proper management is aimed at lowering serum uric acid level below 6.0 mg/dL with xanthine oxidase inhibitors such as allopurinol or febuxostat. Allopurinol and mycophenolate mofetil are safer to use in combination than are allopurinol and azathioprine. Febuxostat is an alternative to allopurinol in patients with allopurinol intolerance or hypersensitivity. Pegloticase is indicated for patients with severe gout in whom allopurinol and febuxostat have not been effective or tolerated.

9 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.

10 Review Update on emerging urate-lowering therapies. 2009

Chohan, Saima / Becker, Michael A. ·Department of Medicine, University of Chicago Pritzker School of Medicine, Illinois, USA. ·Curr Opin Rheumatol · Pubmed #19339925.

ABSTRACT: PURPOSE OF REVIEW: To discuss currently available urate-lowering therapeutic options for gout in the United States and newer therapeutic initiatives in development. RECENT FINDINGS: Currently available urate-lowering drugs include allopurinol and probenecid. These drugs are effective but are often underdosed or underutilized, and caution must be taken in patients with multiple comorbidities. Newer therapeutic agents in development include febuxostat, a nonpurine analogue xanthine oxidase inhibitor, and pegloticase, a pegylated recombinant uricase. SUMMARY: There have been no new US Food and Drug Administration-approved urate-lowering drugs for gout in the past 40 years. Recent advances in therapeutics promise to provide the opportunity for much needed improvement in patient outcomes in this disorder.

11 Review We can make gout management more successful now. 2008

Becker, Michael A / Chohan, Saima. ·Rheumatology Section, Department of Medicine, University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, Chicago, IL 60637, USA. mbecker@medicine.bsd.uchicago.edu ·Curr Opin Rheumatol · Pubmed #18349746.

ABSTRACT: PURPOSE OF REVIEW: The purpose of this editorial review is to identify and comment on factors contributing to the current less-than-optimal state of gout management and to emphasize immediate opportunities to improve management practices affecting many patients with gout. RECENT FINDINGS: Numerous publications document deficits in the current management and clinical outcomes of gout despite detailed understanding of the pathogenesis and pathophysiology of the disorder, the ability to establish the diagnosis with certainty, and the likely effectiveness, for most patients, of available lifestyle and pharmacological interventions. Among impediments to successful gout management are diagnostic inaccuracy; a paucity of validated management recommendations to guide care providers; incomplete patient education about gout and the aims and modalities of management; suboptimal patient adherence, even to demonstrably effective therapeutic recommendations; comorbidities and drug interferences that complicate treatment of gout; patient groups at special risk for progression to chronic tophaceous gout; and limited urate-lowering alternatives. SUMMARY: Recent publication of evidence-based recommendations for the diagnosis and management of gout and the impending availability of new urate-lowering agents suggest that this is an opportune time to initiate professional and patient education efforts toward improved management of this increasingly common disorder.

12 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.

13 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.

14 Clinical Trial Population pharmacokinetics and exposure-uric acid analyses after single and multiple doses of ABT-639, a calcium channel blocker, in healthy volunteers. 2015

An, Guohua / Liu, Wei / Duan, W Rachel / Nothaft, Wolfram / Awni, Walid / Dutta, Sandeep. ·Department of Clinical Pharmacology and Pharmacometrics, Research and Development, AbbVie, 1 North Waukegan Road, North Chicago, Illinois, 60064, USA, guohua-an@uiowa.edu. ·AAPS J · Pubmed #25567367.

ABSTRACT: ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide range of preclinical models of nociceptive and neuropathic pain. In the current first-in-human (FIH) study, the pharmacokinetics, tolerability, and safety of ABT-639 after single- (up to 170 mg) and multiple doses (up to 160 mg BID) were evaluated in healthy volunteers in a randomized, double-blinded, placebo-controlled manner. ABT-639 demonstrated acceptable safety and pharmacokinetic profiles in human. Results from assessment of the routine laboratory variables showed an unexpected statistically significant and clinically relevant decrease in blood uric acid with the increase in ABT-639 dose, which is possibly due to inhibition in URAT1 transporter. Pharmacokinetic/pharmacodynamic models were constructed to characterize the relationship between ABT-639 exposure and uric acid response. The final model was a mechanism-based indirect response pharmacodynamic model with the stimulation of uric acid elimination by ABT-639. The model estimated K in values in males and females were 10.2 and 7.13 μmol/h, respectively. The model estimated K out was 0.033 1/h. ABT-639 concentration that can produce 50% stimulation in uric acid elimination was estimated to be 8,070 ng/mL. Based on the final model, further simulations were conducted to predict the effect of ABT-639 on uric acid in gout patients. The simulation results indicated that, if the urate-lowering response to ABT-639 in gout patients is similar to that in healthy subjects, ABT-639 BID doses of 140 mg or higher would be expected to provide clinically meaningful lowering of blood uric acid levels below the 380 μmol/L solubility limit of monosodium urate.

15 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.

16 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 / Anonymous1481001. ·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 .).

17 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.

18 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 --

19 Article Acute calcium pyrophosphate deposition arthropathy. 2016

Rosen, Thomas / Furman, Janet. ·Thomas Rosen practices at CORE Orthopedics and Sports Medicine in Elk Grove Village, Ill. Janet Furman is an assistant professor in the PA program at Rush University in Chicago, Ill., and practices in the ED at Rush University Medical Center. The authors have disclosed no potential conflicts of interest, financial or otherwise. ·JAAPA · Pubmed #27228038.

ABSTRACT: Acute calcium pyrophosphate deposition (CPPD) arthropathy, also called pseudogout, is common, and becomes more prevalent as patients age. The presenting symptoms are similar to both gout and septic arthritis but may be treated differently. This article describes a typical patient presentation and management from an emergency medicine and orthopedic surgery standpoint.

20 Article Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease. 2016

Mitri, Ghaith / Wittbrodt, Eric T / Turpin, Robin S / Tidwell, Beni A / Schulman, Kathy L. ·1 Medical Director, Mid-America Region, naviHealth, Chicago, Illinois. · 2 Principal Health Outcomes Liaison, Daiichi Sankyo, Parsipanny, New Jersey. · 3 Director and Head, U.S. Health Economics and Outcomes Research, Medical Affairs, Takeda Pharmaceuticals U.S.A., Deerfield, Illinois. · 4 Research Associate, Outcomes Research Solutions, Shrewsbury, Massachusetts. · 5 Research Scientist and Principal, Outcomes Research Solutions, Shrewsbury, Massachusetts. ·J Manag Care Spec Pharm · Pubmed #27023686.

ABSTRACT: BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies. OBJECTIVE: To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD. METHODS: A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings. RESULTS: Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. CONCLUSIONS: Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. DISCLOSURES: No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

21 Article Unusual Electromyographic Findings Associated With Colchicine Neuromyopathy: A Case Report. 2016

Marciniak, Christina / Babu, Ashwin / Ghannad, Leda / Burnstine, Richard / Keeshin, Susan. ·Departments of Physical Medicine and Rehabilitation and Neurology, Northwestern University; and Rehabilitation Institute of Chicago, Room 1154, 345 E. Superior, Chicago, IL 60611. · Department of Physical Medicine and Rehabilitation, Harvard Medical School, and Spaulding Rehabilitation Hospital, Boston, MA. · Midwest Orthopedics at Rush University Medical Center, Chicago, IL. · North Shore Pediatrics, Evanston, IL. · Departments of Physical Medicine and Rehabilitation and Neurology, Chicago, IL. ·PM R · Pubmed #26972360.

ABSTRACT: An 83-year-old man with multiple medical problems, including gout, pseudogout, and renal insufficiency, presented with more than a year of proximal weakness. He had an extensive previous medical workup, including a normal creatinine kinase. His weakness persisted despite endurance and strength training. Electrodiagnostic findings were consistent with a myopathy, although without abnormal spontaneous activity and a length-dependent neuropathy. On the basis of these findings, colchicine was discontinued. The patient experienced marked symptomatic improvement within a week. Myopathies with neuropathies may be found with the use of colchicine. This case was unusual because of the absence of abnormal spontaneous activity and increased creatinine kinase, as typically reported with colchicine myopathy. LEVEL OF EVIDENCE: V.

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 Mutlifocal osseous posttransplantation lymphoproliferative disorder: case report. 2015

Lo, Ryan / Michalicek, Zachary / Lazarus, Martin. ·Department of Radiology, University of Chicago, 5841 South Maryland Avenue, MC 2026, Chicago, IL, 60637, USA, dr.ryan.lo@gmail.com. ·Skeletal Radiol · Pubmed #25680332.

ABSTRACT: Posttransplant lymphoproliferative disorder (PTLD) is a known complication of organ transplantation, but musculoskeletal involvement of PTLD remains very rare. We present a case of recurrent PTLD of the bone in a heart transplant patient that was misdiagnosed as gout for several years. There are only a few cases of osseous PTLD in the literature, and we hope to better characterize its imaging findings on multiple imaging modalities.

24 Article Achieving serum urate goal: a comparative effectiveness study between allopurinol and febuxostat. 2014

Hatoum, Hind / Khanna, Dinesh / Lin, Swu-Jane / Akhras, Kasem S / Shiozawa, Aki / Khanna, Puja. ·President, Hind T. Hatoum and Company; Adjunct Faculty, University of Illinois at Chicago, Chicago, IL. ·Postgrad Med · Pubmed #24685969.

ABSTRACT: BACKGROUND: Febuxostat is recommended as 1 of 2 first-line urate-lowering therapies (ULT) for treating gout in the 2012 American College of Rheumatology Guidelines. Several efficacy trials have compared febuxostat with allopurinol treatment, but real-world comparative data are limited. METHODS: We compared effectiveness of the 2 agents in reaching serum urate (sUA) level goal (< 6 mg/dL) within 6 months (main endpoint), factors impacting the likelihood of reaching goal, and outcomes in allopurinol patients who were switched to febuxostat therapy after failing to reach sUA level goal. Data from the General Electric Electronic Medical Record database on adult patients with newly diagnosed gout, who had started treatment with allopurinol or febuxostat in 2009 or thereafter were analyzed. Descriptive statistics, bivariate analyses, and logistic regressions were used. RESULTS: Allopurinol (n = 17 199) and febuxostat (n = 1190) patients had a mean ± standard deviation (SD) age of 63.7 (± 13.37) years; most patients were men and white. Average daily medication doses (mg) in the first 6 months were 184.9 ± 96.7 and 48.4 ± 15.8 for allopurinol- and febuxostat-treated patients, respectively; 4.8% of allopurinol-treated patients switched to febuxostat, whereas 25.7% of febuxostat-treated patients switched to allopurinol. Febuxostat patients had lower estimated glomerular filtration rate levels, more diabetes mellitus, or tophi at baseline (P < 0.05) and 29.2% and 42.2% of patients in the allopurinol and febuxostat groups achieved goal sUA levels (P < 0.0001). Febuxostat was significantly more effective in patients reaching sUA goal (adjusted odds ratio, 1.73; 95% CI, 1.48-2.01). Older patients and women had greater likelihood of reaching sUA goal level; however, patients with higher Charlson Comorbidity Index scores, blacks, or those with estimated glomerular filtration rates between 15 to ≤ 60 mL/min had reduced likelihood of attaining goal (P < 0.05). Among allopurinol-treated patients who were switched to febuxostat after failing to reach goal, 244 (48.3%) reached goal on febuxostat (median = 62.5 days), with an average 39% sUA level reduction achieved within 6 months. Patients who did not reach goal had a 14.3% sUA level reduction. CONCLUSIONS: The real-life data support the effectiveness of febuxostat in managing patients with gout.

25 Article Smilax riparia reduces hyperuricemia in mice as a potential treatment of gout. 2014

Wu, Xiao-Hui / Yu, Chun-Hao / Zhang, Chun-Feng / Anderson, Samantha / Zhang, Yan-Wen. ·Tang Center for Herbal Medicine Research, University of Chicago, Chicago, Illinois 60637, USA , Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, College of Pharmacy, Tianjin Medical University, Tianjin 300070, China. ·Am J Chin Med · Pubmed #24467548.

ABSTRACT: The roots and rhizomes of Smilax riparia, called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we examined the efficacy of S. riparia in reducing serum uric acid levels in a potassium oxonate-induced hyperuricemia mouse model. We observed that the total saponins of S. riparia could down-regulate renal mURAT1, resulting in the enhancement of urate excretion in the kidney of hyperuricemic mice. These results suggest that S. riparia could be an active anti-gout herbal medicine, which would contribute to the enhancement of uric acid excretion in the kidney.

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