2014 gss updates on gout
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GOUT
SIDNEY ERWIN MANAHAN, MD, FPCP, FPRA
Internal Medicine – Rheumatology
31 January 2014
U P D A T E S O N
T R E A T M E N T
GOUTY ARTHRITIS
“The INTERNIST is expected to diagnose and initiate treatment, continue treatment or
refer for problems and specialized treatment”
Glossary of Disease and Disorders in General IM Practice, Philippine College of Physicians, 2011
25 in 100 will have hyperuricemia
1 in 100 will have gouty arthritis
50 of 100 gout patients have complications
Salido EO, et al. PJIM 2008; 46: 273-6. Manahan L, et al Rheum Int 1985. Dans LF, et
al J Rheum 1997. Dans LF, et al. PJIM 2006. Roberto LC, et al. Poster. PRA 2007
Phases of Gout and Treatment Goals
ACUTE
GOUT Asymptomatic
Hyperuricemia
Terminate flare Prevent repeated flares
Reverse / prevent complications
Prevent gouty
arthritis
INTERVAL
GOUT
CHRONIC
GOUT
Serum Uric Acid (SUA) and Incident Gout
0.0%
10.8%
27.7%
61.1%
0%
20%
40%
60%
80%
<6.0 7.0-7.9 8.0-8.9 >9.0
5 y
ea
r In
cid
en
ce
of
Go
ut
Serum Uric Acid (mg/dl)
Roddy and Doherty, Arthritis Research & therapy 2010; 12: 23
How to treat Asymptomatic Hyperuricemia?
Dietary Prescriptions for Gout and HU
AVOID
• Organ meats
• Drinks with fructose
(corn syrup)
• Alcohol overuse
(esp if with attack
of gout)
LIMIT
• Seafoods
• Sweetened fruit
juices
ENCOURAGE
• Dairy Products
• Vegetables
Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 ACR Guidelines for Management of
Gout. Part 1. Arth Care & Res 2012; 64 (10): 1431-46.
Is Pain VAS
>7/10?
Start
COMBINATION
therapy
Start
MONOTHERAPY
Is there
ADEQUATE* response?
Complete
therapy
REVIEW Diagnosis;
REVISE therapy
Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of
Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
Yes
Yes
No
No
* Improvenent >20% in
24hr or >50% after 24
hr
TREATING ACUTE GOUT
Treating Acute Gout
COLCHICINE NSAIDs STEROIDS
1.0 mg then 0.5
mg TID 12 hours
later
FULL anti-
inflammatory
dose
Prednisone 0.5
mkd for 5-10
days
Triamcinolone
60 mg IM
ACTH 25-40 IU
SC x 1-2 doses COMBINATION 1
COMBINATION 2
COMBINATION 3 IA Steroid AND
Any of the three
Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of
Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
Treating Acute Gout
COLCHICINE NSAIDs STEROIDS
Chronic Kidney Disease St 3-5
Peptic Ulcer
Disease
Heart Failure or
Anticoagulants
Diabetes or Infection
Liver Disease
Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of
Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
Preventing Flares
COLCHICINE NSAIDs STEROIDS
Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of
Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
0.5 mg OD-BID Low doses + PPI
Naproxen 250
mg BID
Pred <10mg/d
DURATION
• 6 months
• 3 months of achieving target SUA if
with no visible tophi
• 6 months of achieving target SUA
and resolution of visible tophi
WHICH EVER IS LONGER
Lowering Serum Uric Acid (SUA)
<6mg/dl For patients without tophi
<5mg/dl For patients with tophi
When to Start Urate Lowering Therapies (ULT)
• At least 2 flares/year
• Presence of tophi
• Radiographic changes of
gouty arthropathy
• Nephrolithiases
• Co-morbid conditions that
may complicate treatment of
gout (CV disease, CKD)
Choosing Among Urate Lowering Therapies (ULTs)
URICOSURICS
Probenecid
Sulfinpyrazone
Losartan
Fenofibrates
XANTHINE OXIDASE
INHIBITORS
Allopurinol
Febuxostat
URICASE
Pegloticase
Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 ACR Guidelines for Management of
Gout. Part 1. Arth Care & Res 2012; 64 (10): 1431-46.
Febuxostat 40 mg/d Allopurinol 100mg/d
Check if target SUA is achieved
40 mg q 2-4 weeks 100mg q 2-4 weeks
Develops adverse event / not tolerated
Shift to Febuxostat Shift to Allopurinol
Target SUA not achieved on max doses
Add uricosuric agent or consider pegloticase
FEBUXOSTAT Selective
Non-purine
ALLOPURINOL Non-selective
purine
WHICH IS BETTER?
FACT (2005) Becker MA, Schumacher HR, et al. NEJM 2005; 353 (23): 2450-61
APEX (2008) Schumacher HR, Becker MA, et al. Arth Rheum 2008; 59(11): 1540-8
FOCUS (2009) Schumacher HR, Becker MA, et al. Rheum 2009; 48: 188-94
EXCEL (2009) Becker MA, Schumacher HR, et al. J Rheum 2009; 36 (6): 1273-82
CONFIRMS (2010) Becker MA, Schumacher HR, et al. Arth Res Ther 2010; 12 (2): R63
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
End Points at Febuxostat 40mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
Gout flares 40 41 0.97 (0.57 to
1.65) 1324 (1)
SUA<6mg% 432 408 1.1 (0.94 to
1.20) 1324 (1)
Serious AE 25 41 0.61 (0.35 to
1.07) 1513 (1)
Withdrawal 104 85 1.2 (0.90 to
1.70) 1513 (1)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
Safety at Febuxostat 40mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
LFT AbN 83 110 0.76 (0.53 to
1.08) 1513 (1)
Skin
reaction 58 73
0.80 (0.54 to
1.17) 1513 (1)
CV Events 50 60 0.84 (0.55 to
1.28) 1513 (1)
HPN 0 0 0 1513 (1)
TOTAL AE 567 573 0.99 (0.91 to
1.08) 1513 (1)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
End Points at Febuxostat 80mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
Gout flares 228 204 1.1 (0.98 to
1.30) 2325 (3)
SUA<6mg% 716 398 1.8 (1.60 to
2.10) 2193 (3)
Serious AE 39 45 0.88 (0.55 to
1.42) 1044 (3)
Withdrawal 265 202 1.3 (1.14 to
1.51) 1044 (3)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
Withdrawals at Febuxostat 80mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
Adv Events 74 71 1.05 (0.80 to
1.39) 1044 (3)
Gout flare 23 9 2.99 (0.70 to
12.79) 1044 (3)
Efficacy 5 2 3.08 (0.55 to
17.20) 1044 (3)
Others 242 194 1.25 (0.90 to
1.74) 1044 (3)
TOTAL 265 202 1.3 (1.14 to
1.51) 1044 (3)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
Safety at Febuxostat 80mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
LFT AbN 61 60 1.03 (0.76 to
1.39) 1044 (3)
Skin
reaction 45 57
0.78 (0.56 to
1.09) 1044 (3)
CV Events 34 36 ** 0 (-0.02 to
0.01) 1044 (3)
HPN 10 1 4.35 (1.25 to
15.09) 1044 (3)
TOTAL AE 591 664 0,94 (0.89 to
0.99) 1044 (3)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
** Risk difference
End Points at Febuxostat 120mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
Gout flares 542 420 1.3 (0.87 to
1.90) 986 (2)
SUA<6mg% 829 384 2.2 (1.90 to
2.50) 880 (2)
Serious AE 58 50 1.16 (0.70 to
1.93) 1513 (1)
Withdrawal 321 236 1.4 (1.12 to
1.66) 1041 (3)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
Withdrawals at Febuxostat 120mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
Adv Events 75 50 1.57 (0.49 to
5.03) 1041 (3)
Gout flare 65 19 3.42 (1.72 to
6.81) 1041 (3)
Efficacy 6 2 ** 0 (0.00 to
0.01) 1041 (3)
Others 186 165 1.13 (0.87 to
1.47) 1041 (3)
TOTAL 321 236 1.36 (1.12 to
1.66) 1041 (3)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
** Risk difference
Safety at Febuxostat 120mg
Outcome Risks (/1000) Relative Risk
(95% CI)
Population
(#Studies) Febuxostat Allopurinol*
LFT AbN 44 50 0.89 (0.51 to
1.53) 1513 (1)
Skin
reaction 35 35
1.00 (0.53 to
1.89) 1513 (1)
CV Events 10 2 ** 0.01 (0.00 to
0.02) 1513 (1)
HPN 12 6 ** 0.01 (-0.01 to
0.02) 1513 (1)
TOTAL AE 715 797 0.90 (0.84 to
0.96) 1513 (1)
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653
* 300 mg if normal renal function, 200 mg if impaired renal function
** Risk difference
Why Choose One Over
the Other?
Dosing Efficacy of Allopurinol
Zhang W et al Ann Rheum Dis 2006; 65: 1312-1324 EULAR Evidence Based Recommendations for Gout
SUA Trend in Theoretical Patient
0 2 4 6 8 10 12 14 16
2
4
6
8
10
Allopurinol
Febuxostat
Duration of treatment (Weeks)
Se
rum
Uric
Ac
id le
ve
ls (
mg
/dl)
Allopurinol*
SUMMARY
• Treat gout at different stages
of the disease
• Discussed differences in the
efficacy and safety of
available xanthine oxidase
inhibitors
Survey of Practices in Gout Therapy
Hamijoyo L, et al. Unpublished 2007.
Treating ACUTE GOUT
Preventing gout FLARES
INDICATIONS for urate lowering therapy
DURATION of urate lowering therapies
67% 12%
77%
6%
5%
LET’S IMPROVE OUTCOMES IN GOUT!
This potential for cure with adequate
long-term treatment makes gout a
rewarding condition for clinicians to
manage.
Perez Ruiz F. Treating to target: a strategy to cure gout. Rheumatology
2009; 48 (supp 2):ii9-ii14.
It will cover the pathogenesis, environment/ genetics, diagnostics, management and
prevention of various rheumatic conditions.
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