This document provides an overview and summary of treatment guidelines for gout. It discusses the different stages of gout including asymptomatic hyperuricemia, acute gout, interval gout, and chronic gout. It reviews guidelines for treating acute gout flares using monotherapy or combination therapies. It also summarizes recommendations for preventing flares and lowering serum uric acid levels through dietary changes and use of urate-lowering therapies such as allopurinol, febuxostat, probenecid, and pegloticase. Head-to-head trials comparing allopurinol and febuxostat are reviewed showing febuxostat is more effective at lowering uric acid levels but has a higher

1. UPDATES ON
GOUT
TREATMENT
SIDNEY ERWIN MANAHAN, MD, FPCP, FPRA
Internal Medicine – Rheumatology
31 January 2014

2. “The INTERNIST is expected to diagnose and
initiate treatment, continue treatment or
refer for problems and specialized
treatment”
GOUTY ARTHRITIS
Glossary of Disease and Disorders in General IM
Practice, Philippine College of Physicians, 2011

3. 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

4. Phases of Gout and Treatment Goals
Asymptomatic
Hyperuricemia
Prevent gouty
arthritis
ACUTE
GOUT
Terminate flare
INTERVAL
GOUT
CHRONIC
GOUT
Prevent repeated flares
Reverse / prevent complications

5. Serum Uric Acid (SUA) and Incident Gout
5 year Incidence of Gout
80%
61.1%
60%
40%
27.7%
20%
10.8%
0.0%
0%
<6.0
7.0-7.9
8.0-8.9
Serum Uric Acid (mg/dl)
Roddy and Doherty, Arthritis Research & therapy 2010; 12: 23
>9.0

6. How to treat
Asymptomatic Hyperuricemia?

7. Dietary Prescriptions for Gout and HU
AVOID
LIMIT
ENCOURAGE
• Organ meats
• Seafoods
• Dairy Products
• Drinks with fructose
(corn syrup)
• Sweetened fruit
juices
• Vegetables
• Alcohol overuse
(esp if with attack
of gout)
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.

8. Is Pain VAS
>7/10?
Yes
TREATING
ACUTE GOUT
Start
COMBINATION
therapy
No
Start
MONOTHERAPY
Is there
ADEQUATE*
response?
Yes
Complete
therapy
No
* Improvenent >20% in
24hr or >50% after 24
hr
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.

9. Treating Acute Gout
COMBINATION 3
IA Steroid AND
Any of the three
COLCHICINE
NSAIDs
STEROIDS
1.0 mg then 0.5
mg TID 12 hours
later
FULL antiinflammatory
dose
Prednisone 0.5
mkd for 5-10
days
Triamcinolone
60 mg IM
COMBINATION 1
ACTH 25-40 IU
SC x 1-2 doses
COMBINATION 2
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.

10. Treating Acute Gout
COLCHICINE
NSAIDs
Chronic Kidney
Disease St 3-5


Peptic Ulcer
Disease


Heart Failure or
Anticoagulants

Diabetes or
Infection
Liver Disease
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.

11. Preventing Flares
COLCHICINE
NSAIDs
STEROIDS
0.5 mg OD-BID
Low doses + PPI
Naproxen 250
mg BID
Pred <10mg/d
DURATION
WHICH
EVER IS
LONGER
• 6 months
• 3 months of achieving target SUA if
with no visible tophi
• 6 months of achieving target SUA
and resolution of visible tophi
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.

12. Lowering Serum Uric Acid (SUA)
<6mg/dl <5mg/dl
For patients without tophi
For patients with tophi

13. 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)

14. Choosing Among
Urate Lowering Therapies (ULTs)
URICOSURICS
XANTHINE
OXIDASE
INHIBITORS
URICASE
Probenecid
Sulfinpyrazone
Allopurinol
Febuxostat
Pegloticase
Losartan
Fenofibrates
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.

15. 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 Allopurinol
Shift to Febuxostat
Target SUA not achieved on max doses
Add uricosuric agent or consider pegloticase

16. ALLOPURINOL
Non-selective
purine
FEBUXOSTAT
Selective
Non-purine
WHICH IS BETTER?

17. 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

18. 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)
* 300 mg if normal renal function, 200 mg if impaired renal function
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

19. 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)
567
573
0.99 (0.91 to
1.08)
1513 (1)
TOTAL AE
* 300 mg if normal renal function, 200 mg if impaired renal function
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

20. 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)
* 300 mg if normal renal function, 200 mg if impaired renal function
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

21. 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)
* 300 mg if normal renal function, 200 mg if impaired renal function
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

22. 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)
* 300 mg if normal renal function, 200 mg if impaired renal function
** Risk difference
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

23. 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)
* 300 mg if normal renal function, 200 mg if impaired renal function
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

24. 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)
* 300 mg if normal renal function, 200 mg if impaired renal function
** Risk difference
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

25. 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)
* 300 mg if normal renal function, 200 mg if impaired renal function
** Risk difference
Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout.
Cochrane Database of Sys Rev 2012; 11: Art No CD008653

26. Why Choose
One Over
the Other?

27. Dosing Efficacy of Allopurinol
Zhang W et al Ann Rheum Dis 2006; 65: 1312-1324
EULAR Evidence Based Recommendations for Gout

28. SUA Trend in Theoretical Patient
Serum Uric Acid levels (mg/dl)
10
8
Allopurinol*
6
Allopurinol
Febuxostat
4
2
0
2
4
6
8
10
12
Duration of treatment (Weeks)
14
16

29. SUMMARY
• Treat gout at different stages
of the disease
• Discussed differences in the
efficacy and safety of
available xanthine oxidase
inhibitors

30. Survey of Practices in Gout Therapy
Treating ACUTE GOUT
12%
67%
Preventing gout FLARES
77%
INDICATIONS for urate lowering therapy
6%
DURATION of urate lowering therapies
5%
Hamijoyo L, et al. Unpublished 2007.

31. 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.

32. It will cover the pathogenesis, environment/
genetics, diagnostics, management and
prevention of various rheumatic conditions.
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