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Gout: HELP
Articles by Lhanoo Gunawardhana
Based on 10 articles published since 2010
(Why 10 articles?)
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Between 2010 and 2020, Lhanoo Gunawardhana wrote the following 10 articles about Gout.
 
+ Citations + Abstracts
1 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.

2 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.

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

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

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

4 Clinical Trial Preservation of renal function during gout treatment with febuxostat: a quantitative study. 2013

Whelton, Andrew / MacDonald, Patricia A / Chefo, Solomon / Gunawardhana, Lhanoo. ·Universal Clinical Research Center, Inc, Hunt Valley, MD, USA. huntvalley@aol.com ·Postgrad Med · Pubmed #23391676.

ABSTRACT: BACKGROUND: Hyperuricemia can accelerate renal decline associated with aging. Chronic kidney disease is frequently seen in patients with hyperuricemia and gout. OBJECTIVES: Assess the impact of urate-lowering therapy on renal function in subjects with gout who were treated with febuxostat for ≤ 48 months. METHODS: Subjects from 2 phase 3 clinical studies were enrolled in the phase 3, long-term, open-label Febuxostat/Allopurinol Comparative Extension Long-Term (EXCEL) study. In the EXCEL study, 1086 subjects initially were treated with febuxostat 80 or 120 mg daily, or allopurinol 300 mg daily. The subjects were permitted to switch between doses of febuxostat and/or allopurinol during the first 6 months of treatment to achieve and maintain a serum uric acid (SUA) level ≥ 3 to < 6 mg/dL. For the analysis presented in this article, data from 551 subjects who received only febuxostat throughout the duration of both the phase 3 and EXCEL studies (≤ 48 months) were used to determine the impact of SUA reduction on estimated glomerular filtration rates (eGFRs). RESULTS: At baseline of the 2 original phase 3 studies, subjects' mean SUA level was 9.8 mg/dL. Greater sustained decreases in subjects' SUA levels were associated with less renal function decline (P < 0.001) by statistical modeling. The study data predicted that for every 1 mg/dL of chronic reduction of SUA level in subjects with gout, there would be a preservation of 1.15 mL/min of eGFR. CONCLUSION: Sustained urate-lowering therapy with febuxostat appears to impede renal decline in patients with gout. The results discussed in this article support similar observations previously reported in 116 hyperuricemic subjects with gout who received febuxostat for ≤ 5 years.

5 Clinical Trial Febuxostat in gout: serum urate response in uric acid overproducers and underexcretors. 2011

Goldfarb, David S / MacDonald, Patricia A / Hunt, Barbara / Gunawardhana, Lhanoo. ·New York Veterans Affairs Medical Center, New York, NY, USA. david.goldfarb@nyumc.org ·J Rheumatol · Pubmed #21572152.

ABSTRACT: OBJECTIVE: Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate (sUA) levels in gouty patients who were either overproducers or underexcretors. METHODS: Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2, 28-day, multicenter, randomized, double-blind, placebo-controlled trial and randomized to receive febuxostat 40 mg, 80 mg, or 120 mg daily, or placebo. The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28. Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid (uUA) from baseline to Day 28. RESULTS: Of the 153 subjects, 118 (77%) were underexcretors (uUA ≤ 800 mg/24 h) and 32 (21%) were overproducers (uUA > 800 mg/24 h); baseline uUA data were missing for 3 subjects. Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28. Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group, for both underexcretors and overproducers. CONCLUSION: Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status.

6 Clinical Trial Renal function in gout: long-term treatment effects of febuxostat. 2011

Whelton, Andrew / Macdonald, Patricia A / Zhao, Lin / Hunt, Barbara / Gunawardhana, Lhanoo. ·Universal Clinical Research Center, Inc., 1737 Beaver Brook Lane, Hunt Valley, MD 21030-1603, USA. huntvalley@aol.com ·J Clin Rheumatol · Pubmed #21169856.

ABSTRACT: BACKGROUND: The association between hyperuricemia, gout, and impaired renal function has long been recognized. Recent data provide evidence for the causal relationship between elevated serum urate (sUA) and renal changes, leading to declines in glomerular filtration rates. In healthy adults, glomerular filtration rate wanes with age. Urate-lowering therapy (ULT) with allopurinol has been shown to stabilize or reverse this. OBJECTIVE: Here we examine the long-term effects of ULT with febuxostat on estimated glomerular filtration rate (eGFR). METHODS: This is a post hoc analysis of the Febuxostat Open-label Clinical trial of Urate-lowering efficacy and Safety study, during which 116 hyperuricemic gout subjects received daily doses of febuxostat (40, 80, or 120 mg) for up to 5 years. sUA concentrations and eGFR were assessed regularly. Results were stratified by mean change in sUA from baseline. Mathematical modeling was used to predict the effect of sUA reduction on eGFR. RESULTS: Maintenance or improvement in eGFR was inversely correlated with the quantitative reduction in sUA from baseline. For every 1 mg/dL decrease in sUA, the model projected an expected improvement in eGFR of 1 mL/min from the untreated value. CONCLUSION: Individuals with the greatest reductions in sUA may experience reduced rates of renal deterioration or even stabilization of renal function. Further studies examining the impact of long-term ULT on renal function in hyperuricemic gout patients are needed to both confirm our results and verify if improvements in renal function are feasible in such patients.

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

White, William B / Saag, Kenneth G / Becker, Michael A / Borer, Jeffrey S / Gorelick, Philip B / Whelton, Andrew / Hunt, Barbara / Castillo, Majin / Gunawardhana, Lhanoo / 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 .).

8 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.

9 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.

10 Minor Cardiovascular Safety of Febuxostat. 2018

White, William B / Gunawardhana, Lhanoo. ·University of Connecticut School of Medicine, Farmington, CT wwhite@uchc.edu · Takeda Development Center Americas, Deerfield, IL ·N Engl J Med · Pubmed #30332566.

ABSTRACT: -- No abstract --