2014 GSS Updates on Gout

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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