Hello; I'm Dr. Jonathan Kay, Director of Clinical Research in the Division of Rheumatology at the University of Massachusetts Memorial Medical Center, and Professor of Medicine at the University of Massachusetts Medical School in Worcester. Welcome to this Medscape video blog from the European League Against Rheumatism 2010 Annual Meeting in Rome. I'd like to highlight some interesting presentations on gout from this year's meeting.
The first study is by Michael Becker and colleagues,[1] from the University of Chicago [Chicago, Illinois], who looked at the urate-lowering efficacy and safety of daily gout treatment with febuxostat or allopurinol. They studied 1555 patients with gout and hyperuricemia, defined as a serum uric acid level of ≥ 8 mg/dL, from the 28-week APEX trial and the 52-week FACT trial. Patients were prophylaxed with either colchicine or naproxen during the first 8 weeks of treatment.
The rates of urate-lowering endpoints (a serum uric acid level of < 6.0 mg/dL, < 5.0 mg/dL, and < 4.0 mg/dL) achieved were significantly greater in the febuxostat 80-mg and febuxostat 120-mg groups than in the allopurinol 300-mg (taken by mouth daily) group. The rates of adverse events were similar across groups, but the limitation of this study is that it compared 2 doses of febuxostat with only 1 dose of allopurinol, that being 300 mg taken by mouth daily. We know that there are some patients who just don't respond adequately to that dose of allopurinol and who require higher doses of allopurinol -- up to 800 mg/day or 900 mg/day. Allopurinol can and should be used at doses higher than 300 mg taken by mouth daily in some patients who just don't respond adequately. It may be that higher doses of allopurinol are equivalent to febuxostat at those doses, but we have to take this study for what it shows us.
The next presentation is by Schlesinger and colleagues,[2] from the University of Medicine and Dentistry in New Jersey Robert Wood Johnson Medical School [New Brunswick, New Jersey], with colleagues at the Taipei Veterans General Hospital [Taipei City, Taiwan], and colleagues from Novartis Pharma. This study looked at the efficacy of canakinumab, a fully human monoclonal antibody, against interleukin-1-beta in the prevention of flares in gout patients initiating allopurinol therapy. This was a 24-week, double-blind, double-dummy study of 432 patients initiating treatment with allopurinol 300 mg taken by mouth daily. Patients were randomly sampled to receive single subcutaneous doses of canakinumab every 4 weeks or colchicine 0.5 mg taken by mouth daily for 16 weeks.
The proportion of patients experiencing flares was lower for all of the canakinumab-treated groups compared with the colchicine-treated patients. The rates of flares in the canakinumab-treated groups ranged from 13.5% (among those receiving canakinumab 100 mg subcutaneously every 4 weeks) to 23.6% (in those receiving canakinumab 25 mg subcutaneously every 4 weeks), compared with colchicine, which was 43.9%. All comparisons were statistically significant. The rates of adverse events were about 52% for the colchicine-treated patients and 44%-51% in the various canakinumab-treated groups. There were similar rates of adverse events in both groups.
The authors concluded that, in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares when compared with colchicine, and it was very well tolerated. However, the limitation of this study is that it only used colchicine 0.5 mg taken by mouth daily. In my clinical practice, I typically use colchicine 0.6 mg, taken by mouth twice daily, in individuals with normal kidney function. This study really compared canakinumab with an underdose of colchicine in most of those patients.
The convenience of once-monthly subcutaneous dosing vs daily oral prophylaxis may be an advantage to canakinumab, but the relative cost of a biologic agent (even used subcutaneously once monthly) to an oral medication, such as colchicine, may be substantial, and has to be considered when choosing therapy for patients.
The next study is one by Perez-Ruiz and colleagues,[3] from the Hospital de Cruces in Vizcaya, Spain. This study looked at the efficacy and safety of a urate transporter inhibitor (URAT1 inhibitor) called RDEA594, which is a novel uricosuric agent. They studied this as a single agent in hyperuricemic patients with gout. They studied 10 patients with a serum uric acid of ≥ 8 mg/dL and found that treatment with this molecule resulted in robust reductions in the serum urate in underexcretors. The serum uric acid level dropped below 6 mg/dL in 4 of 10 patients treated with 200 mg/day, and in 6 of 10 patients treated with 400 mg/day for 2 weeks. Of the 6 patients in this group who had mild-to-moderate renal insufficiency, 5 patients achieved a response with a serum uric acid of < 6 mg/dL on RDEA594.
The authors concluded that RDEA594 produced robust reductions in serum uric acid after 2 weeks of treatment in patients with and without renal insufficiency. Normal levels of total urate were excreted and normal urate clearance was achieved. Also, patients tolerated RDEA594 quite well.
Another study by the same authors[4] looked at the efficacy and safety of RDEA594 in combination with allopurinol in patients with gout. They looked at 28 gout patients with a serum uric acid level of ≥ 9 mg/dL. Patients were treated with allopurinol 300 mg taken by mouth daily for 1 week, and serum uric acid levels were reduced from > 9 mg/dL to 6.3 mg/dL (mean). This was a 40% reduction. Adding RDEA594 200 mg for an additional week produced about a 50% reduction in serum uric acid from a baseline of about 10 mg/dL. Increasing RDEA594 to 400 mg for an additional week resulted in nearly a 55% reduction of serum uric acid to a mean of 4.6 mg/dL. All patients receiving the combination of allopurinol and RDEA594 achieved serum uric acid levels below 6 mg/dL, and 80% of the patients achieved levels below 5 mg/dL. The combination was well tolerated with no serious adverse events.
The authors concluded that this combination of RDEA594 and allopurinol produced a substantial reduction in serum uric acid and normalization of urate excretion in gout patients. Thus, this urate transporter inhibitor, RDEA594, may be used in combination with allopurinol to initially reduce the serum uric acid levels significantly, and then [allopurinol alone can be used to] maintain the patient's normal uric acid level.
I hope that this information from the 2010 European League Against Rheumatism Annual Meeting in Rome about gout is helpful to your practice, and I thank you very much for taking the time to watch this Medscape video blog.
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COMMENTARY
EULAR 2010 Gout Highlights From Jonathan Kay, MD
Jonathan Kay, MD
DisclosuresJuly 01, 2010
Hello; I'm Dr. Jonathan Kay, Director of Clinical Research in the Division of Rheumatology at the University of Massachusetts Memorial Medical Center, and Professor of Medicine at the University of Massachusetts Medical School in Worcester. Welcome to this Medscape video blog from the European League Against Rheumatism 2010 Annual Meeting in Rome. I'd like to highlight some interesting presentations on gout from this year's meeting.
The first study is by Michael Becker and colleagues,[1] from the University of Chicago [Chicago, Illinois], who looked at the urate-lowering efficacy and safety of daily gout treatment with febuxostat or allopurinol. They studied 1555 patients with gout and hyperuricemia, defined as a serum uric acid level of ≥ 8 mg/dL, from the 28-week APEX trial and the 52-week FACT trial. Patients were prophylaxed with either colchicine or naproxen during the first 8 weeks of treatment.
The rates of urate-lowering endpoints (a serum uric acid level of < 6.0 mg/dL, < 5.0 mg/dL, and < 4.0 mg/dL) achieved were significantly greater in the febuxostat 80-mg and febuxostat 120-mg groups than in the allopurinol 300-mg (taken by mouth daily) group. The rates of adverse events were similar across groups, but the limitation of this study is that it compared 2 doses of febuxostat with only 1 dose of allopurinol, that being 300 mg taken by mouth daily. We know that there are some patients who just don't respond adequately to that dose of allopurinol and who require higher doses of allopurinol -- up to 800 mg/day or 900 mg/day. Allopurinol can and should be used at doses higher than 300 mg taken by mouth daily in some patients who just don't respond adequately. It may be that higher doses of allopurinol are equivalent to febuxostat at those doses, but we have to take this study for what it shows us.
The next presentation is by Schlesinger and colleagues,[2] from the University of Medicine and Dentistry in New Jersey Robert Wood Johnson Medical School [New Brunswick, New Jersey], with colleagues at the Taipei Veterans General Hospital [Taipei City, Taiwan], and colleagues from Novartis Pharma. This study looked at the efficacy of canakinumab, a fully human monoclonal antibody, against interleukin-1-beta in the prevention of flares in gout patients initiating allopurinol therapy. This was a 24-week, double-blind, double-dummy study of 432 patients initiating treatment with allopurinol 300 mg taken by mouth daily. Patients were randomly sampled to receive single subcutaneous doses of canakinumab every 4 weeks or colchicine 0.5 mg taken by mouth daily for 16 weeks.
The proportion of patients experiencing flares was lower for all of the canakinumab-treated groups compared with the colchicine-treated patients. The rates of flares in the canakinumab-treated groups ranged from 13.5% (among those receiving canakinumab 100 mg subcutaneously every 4 weeks) to 23.6% (in those receiving canakinumab 25 mg subcutaneously every 4 weeks), compared with colchicine, which was 43.9%. All comparisons were statistically significant. The rates of adverse events were about 52% for the colchicine-treated patients and 44%-51% in the various canakinumab-treated groups. There were similar rates of adverse events in both groups.
The authors concluded that, in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares when compared with colchicine, and it was very well tolerated. However, the limitation of this study is that it only used colchicine 0.5 mg taken by mouth daily. In my clinical practice, I typically use colchicine 0.6 mg, taken by mouth twice daily, in individuals with normal kidney function. This study really compared canakinumab with an underdose of colchicine in most of those patients.
The convenience of once-monthly subcutaneous dosing vs daily oral prophylaxis may be an advantage to canakinumab, but the relative cost of a biologic agent (even used subcutaneously once monthly) to an oral medication, such as colchicine, may be substantial, and has to be considered when choosing therapy for patients.
The next study is one by Perez-Ruiz and colleagues,[3] from the Hospital de Cruces in Vizcaya, Spain. This study looked at the efficacy and safety of a urate transporter inhibitor (URAT1 inhibitor) called RDEA594, which is a novel uricosuric agent. They studied this as a single agent in hyperuricemic patients with gout. They studied 10 patients with a serum uric acid of ≥ 8 mg/dL and found that treatment with this molecule resulted in robust reductions in the serum urate in underexcretors. The serum uric acid level dropped below 6 mg/dL in 4 of 10 patients treated with 200 mg/day, and in 6 of 10 patients treated with 400 mg/day for 2 weeks. Of the 6 patients in this group who had mild-to-moderate renal insufficiency, 5 patients achieved a response with a serum uric acid of < 6 mg/dL on RDEA594.
The authors concluded that RDEA594 produced robust reductions in serum uric acid after 2 weeks of treatment in patients with and without renal insufficiency. Normal levels of total urate were excreted and normal urate clearance was achieved. Also, patients tolerated RDEA594 quite well.
Another study by the same authors[4] looked at the efficacy and safety of RDEA594 in combination with allopurinol in patients with gout. They looked at 28 gout patients with a serum uric acid level of ≥ 9 mg/dL. Patients were treated with allopurinol 300 mg taken by mouth daily for 1 week, and serum uric acid levels were reduced from > 9 mg/dL to 6.3 mg/dL (mean). This was a 40% reduction. Adding RDEA594 200 mg for an additional week produced about a 50% reduction in serum uric acid from a baseline of about 10 mg/dL. Increasing RDEA594 to 400 mg for an additional week resulted in nearly a 55% reduction of serum uric acid to a mean of 4.6 mg/dL. All patients receiving the combination of allopurinol and RDEA594 achieved serum uric acid levels below 6 mg/dL, and 80% of the patients achieved levels below 5 mg/dL. The combination was well tolerated with no serious adverse events.
The authors concluded that this combination of RDEA594 and allopurinol produced a substantial reduction in serum uric acid and normalization of urate excretion in gout patients. Thus, this urate transporter inhibitor, RDEA594, may be used in combination with allopurinol to initially reduce the serum uric acid levels significantly, and then [allopurinol alone can be used to] maintain the patient's normal uric acid level.
I hope that this information from the 2010 European League Against Rheumatism Annual Meeting in Rome about gout is helpful to your practice, and I thank you very much for taking the time to watch this Medscape video blog.
Medscape Rheumatology © 2010 WebMD, LLC
Cite this: Jonathan Kay. EULAR 2010 Gout Highlights From Jonathan Kay, MD - Medscape - Jul 01, 2010.
References
Authors and Disclosures
Authors and Disclosures
Author(s)
Jonathan Kay, MD
Professor of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; Director of Clinical Research, Division of Rheumatology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
Disclosure: Jonathan Kay, MD, has disclosed the following relevant financial relationships:
Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Array BioPharma Inc.; Bristol-Myers Squibb Company; Celgene Corporation; Centocor, Inc.; Roche; sanofi-aventis; UCB Pharma, Inc.
Have a 5% or greater equity interest in: Roche; sanofi-aventis