Claudine G Jennings1, Isla S Mackenzie2, Rob Flynn2, Ian Ford3, George Nuki4, Raffaele De Caterina5, Philip L Riches4, Stuart H Ralston4, Thomas M MacDonald2. 1. Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK. Electronic address: claudine@memo.dundee.ac.uk. 2. Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK. 3. University of Glasgow, Robertson Centre for Biostatistics, UK. 4. Western General Hospital, Centre for Molecular Medicine, University of Edinburgh, Edinburgh, UK. 5. Cardiovascular Division, G d'Annunzio University, SS. Annunziata Hospital, and Center of Excellence on Aging (Ce.S.I), Chieti, Italy.
Abstract
OBJECTIVES:European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many gout patients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels. METHOD: The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients. RESULTS: Of 400 patients, 144 (36%) had urate levels ≥357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal. CONCLUSION: Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients.
RCT Entities:
OBJECTIVES: European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many goutpatients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels. METHOD: The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients. RESULTS: Of 400 patients, 144 (36%) had urate levels ≥357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal. CONCLUSION: Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients.
Authors: Theodore R Fields; Adam Rifaat; Arthur M F Yee; Dalit Ashany; Katherine Kim; Matthew Tobin; Nicole Oliva; Kara Fields; Monica Richey; Shanthini Kasturi; Adena Batterman Journal: Semin Arthritis Rheum Date: 2016-10-24 Impact factor: 5.532
Authors: Hamish Farquhar; Ana B Vargas-Santos; Huai Leng Pisaniello; Mark Fisher; Catherine Hill; Angelo L Gaffo; Lisa K Stamp Journal: Rheumatol Adv Pract Date: 2021-01-04
Authors: Richard O Day; Lauren J Frensham; Amy D Nguyen; Melissa T Baysari; Eindra Aung; Annie Y S Lau; Nicholas Zwar; Jennifer Reath; Tracey Laba; Ling Li; Andrew McLachlan; William B Runciman; Rachelle Buchbinder; Robyn Clay-Williams; Enrico Coiera; Jeffrey Braithwaite; H Patrick McNeil; David J Hunter; Kevin D Pile; Ian Portek; Kenneth Mapson WIlliams; Johanna I Westbrook Journal: BMJ Open Date: 2017-10-16 Impact factor: 2.692