gout 2012: updates to an old disease

GOUT 2012: Updates to an Old Disease

Assumptions

• Correct Diagnosis

• Consider Co-morbid conditions

• Evaluate for Drug interactions

“The ACR gout guidelines are designed

to emphasize safety and quality of

therapy and to reflect best practice.”

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. 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.

Levels of Evidence

A Meta-analyses

>1 Randomized Clinical Trial

B Single Randomized Clinical Trial

Non-Randomized Studies

C Standards of Care

Case Studies

Expert Consensus

Nomenclature (Acute)

1 2 3 4 5 6 7 8 9 10

SEVERITY (Pain VAS)

DURATION (from onset of symptoms)

0 12 24 36

1 2 3 4 5 6 7 8 9 10

FREQUENCY (No of flares/ year)

Nomenclature

JOINT INVOLVEMENT

• Few small joints

• 1 or 2 large joints

• Polyarthritis • 4 or more joints

involving >1 region

• 3 large joints

Nomenclature (CTG)

MILD MODERATE SEVERE

Affects 1 joint Affects 2-4 joints Simple tophi in >4 joints

Stable disease Stable disease OR

Simple tophi Simple tophi >1 Unstable tophus

Domains in Gout Care

• Acute Gout

• Prophylaxis

• Urate Lowering Therapy

• Chronic Tophaceous 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. 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.

ACUTE GOUT a.k.a. GOUT FLARE

Self limited attack of joint inflammation

Treating Acute Gout

• Treat with pharmacologic therapy (C)

• Best started within 24 hours(C)

• Do not interrupt those on established urate-

lowering therapy (C)

• Educate patient on

– Initiating treatment when w/ a flare (B)

– Effective urate lowering being “curative” (B)

Choosing an Anti-Inflammatory

Pain VAS

<7/10

Start

MONOTHERAPY (A)

Start

COMBINATION

THERAPY (C)

Yes

No

CONSIDER

• Patient preference

• Prior response to meds

• Associated co-morbids

NSAIDs in Acute Gout

• Full anti-inflammatory dose/ acute pain

– Naproxen (A)

– Indomethacin (A)

– Sulindac (B)

– Other NSAIDs (B or C)

– Etoricoxib (A)

– High dose Celecoxib (B)

• Continue until flare completely resolves (C)

Colchicine in Acute Gout

• Best if given <36 hours of onset

• Dosing regimen

– 1.2 mg initially then 0.6 mg after 1 hour then 0.6 mg

BID until acute gout resolves (A)

– 1.0 mg initially then 0.5 mg after 1 hour then 0.5 mg

TID until acute gout resolves (C)

• Do not give IV

• Reduce in moderate-severe CKD

• Caution with clarithromycin, erythromycin,

cyclosporin and disulfiram

Steroids in Acute Gout

• Oral or IA steroids if 1-2 joints involved (B)

• IA steroid dose depends on joint size (B)

• Recommended dosing

– Prednisone 0.5 mkd for 5-10 days (A)

– Prednisone 0.5 mkd for 2-5 days then taper

for 7-10 days (C)

– Triamcinolone 60 mg IM with oral steroids (C)

– No consensus for ACTH (A)

Combination Therapy in Acute Gout

• Colchicine with NSAIDs

• Colchicine with Steroids

• IA Steroids with Colchicine/ NSAIDs/ Oral

Steroids

• Consider topical ice application (B)

Treating the Patient on NPO

• IA steroids for 1-2 large joints (B)

• IV or IM Methylprednisolone (or equivalent)

0.5 – 2.0 mkd (B)

• ACTH 25-40 IU SC (A)

• No consensus on IM Ketorolac or IM

Triamcinolone (C)

Contraindications

CONDITION NSAIDs Colchicine Steroids

Chronic Kidney Disease St 3-5

Peptic Ulcer Disease

Heart Failure

Anti-coagulants/ platelets

Diabetes Mellitus

Infection

Liver Disease

Continuing Acute Gout Care

INADEQUATE

RESPONSE

<20% in 24H

or <50% after

24H

REVIEW the diagnosis

CONSIDER

• Shift to other drug (C)

• Combine therapy (C)

• Anakinra 100 mg SC for

3 days (B)

• Canakinumab 150 mg

SC single dose (A)

COMPLETE

TREATMENT

Yes

No

PROPHYLAXIS To be started in all patients in whom

Urate Lowering Therapy is indicated

Drugs for Prophylaxis

• First Line Drugs

– Colchicine 0.5 – 0.6 mg OD-BID (A)

– Naproxen 250 mg BID + PPI (C)

• Alternate Agents

– Prednisone <10mg/d (C)

• Lack of consensus on off-label anti-IL-1 (A)

Duration of Prophylaxis

Choose the greater of the following:

• 6 months duration (A)

• 3 months of achieving target BUA in patients

without tophi (B)

• 6 months of achieving target BUA AND

resolution of previously noted tophi on PE (C)

URATE LOWERING THERAPY

Pharmacologic and Non-Pharmacologic

Diet and Lifestyle Changes

AVOID LIMIT ENCOURAGE

Organ meats (B)

Drinks with fructose(C)

Alcohol overuse (B)

Alcohol during an acute

attack (C)

Seafood (B)

Sweetened fruit juices (C)

Sugar (C)

Salt (C)

Low fat or non-fat dairy

products (B)

Vegetables (C)

Evaluating Hyperuricemia (C)

• Educate the patient (B)

– Diet and lifestyle changes

– Disease, treatment and objectives

– Role of hyperuricemia and targets

• Consider eliminating non-essential meds that

increase serum uric acid (C)

• Evaluate for co-morbid conditions and

contributors to hyperuricemia (C)

• Assess gout disease burden

Checklist

COMORBIDS (C)

• Obesity

• Alcohol intake

• Metabolic Syndrome and

components

• Kidney disease

• Lead intoxication

• Myeloprolif/ lymphoprolif

disorders

• Psoriasis

LABORATORIES

• Urinalysis

• Renal ultrasound

• CBC

• Urine uric acid

determination (C)

– Gout < 25 y/o

– Nephrolithiases

Indications for ULT

• Evidence of tophus/tophi (A)

• Frequent attacks (>2/year) (A)

• History of nephrolithiases (C)

• Chronic Kidney Disease Stage 2-5 (C)

Target Blood Uric Acid

<6 mg/dl For most gout scenarios

(if without visible tophi)

(A)

<5 mg/dl For more durable

improvement and patients

with visible tophi (B)

Urate Lowering Therapy

• First Line Agents (A)

– Allopurinol 100-800 mg/d

– Febuxostat 40-120 mg/d

• Alternative Therapy (B)

– Probenecid (except when Cr Cl <50ml/min and history

of urolithisases)

• Can be started during an attack(!) PROVIDED

effective anti-inflammatory therapy has been

given (C)

Allopurinol Dosing Guide

• Starting dose <100mg/d (B)

– For CKD 4-5, starting dose is 50mg/d (B)

• Titrate up every 2-5 weeks (C)

• Dose of >300mg/d can be used provided patient

is monitored for AHS and other AE (B)

– Pruritus, Rash, Inc LFT, Eosinophilia

Allopurinol Dosing Guide

Maximum Recommended

Allopurinol Dose Based on Crea

Clearance

Crea Cl (ml/min) Dose

0 100 mg q 3 days

10 100 mg q 2 days

20 100 mg/day

40 150 mg/day

60 200 mg/day

80 250 mg/day

100 300 mg/day

120 350 mg/day

Pharmacogenetics for AHS

Patients at high risk for AHS should consider

screening for HLA-B*5801 (A)

– Korean descent with CKD 3 or worse (A)

– Han Chinese

– Thai

Approach to ULT

• Titrate XOI to max recommended dose (A)

• If up-titration is not tolerated or target BUA is

not achieved, consider shift to other XOI (C)

• If target BUA is not achieved, start combination

therapy by adding a uricosuric (B)

• Last option, if still unable to achieve targets on

oral ULT, is to give PEGLOTICASE (A)

Consider referring when…

• Unclear etiology of hyperuricemia

• Refractory gout

• Difficulty in achieving target BUA

• Multiple or serious AE from ULT

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