Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study

Schumacher, H. Ralph; Becker, Michael A.; Lloyd, Elisabeth A.; MacDonald, Penny A.; Lademacher, Christopher

doi:10.1093/rheumatology/ken457

Cited by 229 publications

(163 citation statements)

References 26 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…The proportion of patients with gout flares requiring treatment declined over 52 weeks, similar to that observed in other studies with febuxostat or allopurinol 5, 6, 8. Longer‐term treatment may be needed to further reduce gout flares, as well as to dissolve baseline tophi, particularly to demonstrate treatment effect differences 24, 25.…”

Section: Discussionsupporting

confidence: 74%

Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial

Dalbeth

Jones

Terkeltaub

et al. 2017

Arthritis & Rheumatology

135

137

View full text Add to dashboard Cite

ObjectiveTo investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12‐month phase III trial in patients with tophaceous gout.MethodsPatients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate‐lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data.ResultsPatients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg.ConclusionTreatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy.

show abstract

Section: Discussionsupporting

confidence: 74%

Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial

Dalbeth

Jones

Terkeltaub

et al. 2017

Arthritis & Rheumatology

135

137

View full text Add to dashboard Cite

show abstract

“…Clinical trial data comparing allopurinol with febuxostat were available over variable time periods (from 6 months up to 60 months). 5,6,13,21 The first-year probabilities used in the economic model were pooled estimates based on information from 2 randomized controlled trials (RCTs) for allopurinol and febuxostat: the Febuxostat versus Allopurinol Control Trial (FACT; n = 762) observed over 52 weeks and the 28-week Allopurinol and Placebo-controlled Efficacy study of febuXostat (APEX). 6,13 This approach was appropriate because the 2 clinical trials, FACT and APEX, used identical patient populations and efficacy and safety endpoints.…”

Section: ■■ Methodsmentioning

confidence: 99%

“…5 Additional long-term data for urate-lowering and clinical efficacy and safety were obtained from a previously published study and the 5-year Febuxostat Open-label Clinical Trial of Urate-Lowering Efficacy and Safety (FOCUS) extension study. 17,21 Since the mortality rates across both treatment arms did not significantly differ, it was assumed that the transition probabilities to death were identical for both treatment arms. 24 The model was designed from the health care payer perspective in the United States.…”

Section: Resource Use and Base-case Undiscounted Cost Values And Rangmentioning

confidence: 99%

Cost-Effectiveness Analysis of Allopurinol Versus Febuxostat in Chronic Gout Patients: A U.S. Payer Perspective

Gandhi

Gentry²,

Ma³

et al. 2015

JMCP

View full text Add to dashboard Cite

BACKGROUND: Gout is a chronic inflammatory condition associated with poor urate metabolism. Xanthine oxidase inhibitors such as allopurinol and febuxostat are recommended to reduce uric acid levels and to prevent gout attacks in adult patients. Under budget-driven constraints, health care payers are faced with the broader challenge of assessing the economic value of these agents for formulary placement. However, the economic value of allopurinol versus febuxostat has not be assessed in patients with gout over a 5-year time period in the United States.

show abstract

“…However, there are no active or completed clinical trials evaluating the use of febuxostat for this indication (57). Febuxostat does seem to be efficacious in the treatment of hyperuricemia associated with gout (58,59). Because its mechanism of action is similar to that of allopurinol, febuxostat would not be expected to decrease the accumulation of xanthine or the risk for xanthine stone formation.…”

Section: Febuxostatmentioning

confidence: 99%

Onco-Nephrology

Wilson

Berns

2012

Clinical Journal of the American Society of Nephrology

123

View full text Add to dashboard Cite

SummaryTumor lysis syndrome (TLS) describes the clinical and laboratory sequelae that result from the rapid release of intracellular contents of dying cancer cells. It is characterized by the release of potassium, phosphorous, and nucleic acids from cancer cells into the blood stream, with the potential to cause hyperkalemia; hyperphosphatemia and secondary hypocalcemia; hyperuricemia; AKI; and, should usual homeostatic mechanisms fail, death. TLS most commonly follows treatment of hematologic malignancies, such as acute lymphocytic or lymphoblastic leukemia, acute myeloid leukemia, and Burkitt lymphoma, but also occurs after treatment of other bulky or rapidly growing tumors, particularly if the patient is highly sensitive to the effects of cytotoxic chemotherapy. Prevention and treatment depend on prompt recognition of patients at risk, volume repletion, allopurinol, rasburicase (a novel recombinant urate oxidase), and, when indicated, dialysis.

show abstract

Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study

Abstract: Long-term treatment with febuxostat resulted in durable maintenance of sUA < 6.0 mg/dl for most subjects. There was nearly complete abolition of gout flares in patients completing the study. Baseline tophi resolved in a majority of subjects.

Cited by 229 publications

References 26 publications

Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial

Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial

Cost-Effectiveness Analysis of Allopurinol Versus Febuxostat in Chronic Gout Patients: A U.S. Payer Perspective

Onco-Nephrology

Contact Info

Product

Resources

About