GOUT TREATMENT

GOUT TREATMENT

• Gout prevalence doubled over the last 20 yrs.• Factors? - longevity - diuretic use - low dose ASA - obesity - end stage renal disease - hypertension - metabolic syndrome

• Treatment: pharmacologic and non-pharm.

CORE ASPECTS OF MANAGEMENT

• Patient Education

• Weight Loss

- obesity is an independent risk factor for gout

Boston Vets Admin. Aging Study Am. J. Med 1987;82:421

Johns Hopkins Precursors Study Rheum Dis Clin. NA 1990;16:539

Health Professional F/U study Arch Int. Med. 2005;165:742

Nurses Health Study A+R 2005;52(suppl 9):S733

CORE ASPECTS OF MANAGEMENT

• Diet - purine rich meat and fish correlated with ↑

SUA/gout

- no assoc. with total protein or purine rich vegetables

- low fat dairy products may be protective

- Vitamin C is uricosuric Choi HK et al. Arch Int Med 2005;165:742

A+R 2005;52:283 and 52:1843

NEJM 2004;350:1093

CORE ASPECTS OF MANAGEMENT

• Alcohol

- beer > liquor associated with ↑ SUA and gout risk

- wine imposes no gout risk and may be protective

Arthritis Care Res 2004;51:1023

Lancet 2004;363:1277

Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

MODIFICATION OF CO-MORBIDITIES/RISK FACTORS

• Raised serum urate and increased risk of gout with:

- obesity - hyperlipidemia - hyperglycemia/insulin resistance - hypertension - (smoking) - diuretic use

GOUT - TREATMENT

1. terminate acute attack

2. provide rapid, safe pain/anti-inflammatory relief

3. prevent complications• destructive arthropathy• tophi• renal stones

GOALS:

Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

ACUTE GOUT TREATMENT

Agents:

1. NSAIDS

2. Corticosteroids

3. Colchicine

ACUTE GOUT - TREATMENT

•DO NOT START A URATE LOWERING DRUG (eg: allopurinol) DURING AN ACUTE ATTACK

• IF ON A URATE LOWERING DRUG, DO NOT STOP OR ADJUST DOSE.

ACUTE GOUT - TREATMENT

A. Colchicine• must be started in first 24 hours• narrow therapeutic - toxic ratio

i.e.,: GI upset in 80%• limited therapeutic use in acute gout• other side effects: bone marrow

suppression, renal failure, CHF, death

ACUTE GOUT - TREATMENT

B. NSAIDS COX-1 and COX-2

• use in patients without contraindication• use maximum dose/potent NSAID

e.g., Indomethacin 50 mg po t.i.d.

Diclofenic 50 mg po t.i.d.

Ketorolac 10 mg q4-6hrs

• continue until pain/inflammation absent for 48 hours

ACUTE GOUT - TREATMENT

C. Corticosteroid• use when • NSAIDS risky or contraindicated

e.g.,: elderly

hypertensive

peptic ulcer disease

renal impairment

liver impairment

• use when • NSAIDS ineffective

ACUTE GOUT - TREATMENT

C. Corticosteroid • mode of administration

1. intra-articular with drainage R/O sepsise.g.,) depomedrol 40-80 mg with lidocaine

2. oral prednisone 30-40 mg qd for 3-4 days. Then taper by 5 mg every 2-3 days and stop over 1-2 weeks

GOUT - URATE LOWERING TREATMENT

General Principles:1. never start a uric lowering agent during an acute attack

2. hyperuricemia with an acute inflammatory arthritis is not necessarily gout * crystal analysis

3. asymptomatic hyperuricemia is not an indication for treatment. Though … SUA may be an additional independent risk factor for CV disease

Am J Med 2005; 118:816 J. Rheum 2005; 32(5):906 Arch Int Med 2004; 164(14);1546

GOUT - URATE LOWERING TREATMENT

General Principles:• gout is a true urate deposition disease ie: urate crystals are present• halt crystal formation - cure the disease• maintain SUA level below 360µmol/l ie: below the tissue saturation for MSU A+R 2002; 47:555

J Rheum 2001; 28:577 Ann Int. Med. 2005; 143:499

Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

URATE LOWERING TREATMENT

Who to treat? 1. tophi 2. gouty athropathy 3. radiographic changes of gout 4. multiple joint involvement 5. nephrolithiasis controversy: when to treat in early disease?

URATE LOWERING DRUGS

Uricosurics – inhibit URAT11.Probenecid and Sulfinpyrazone

- require: good renal function no ASA good urine output day and night

- therefore limited use

2. Losartan - no trials in gout management

Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

URATE LOWERING DRUGS

Allopurinol - an inhibitor of xanthine oxidase

• start low eg) 50-100 mg qd• increase by 50-100mg every 2-3 weeks

according to symptoms and measured SUA• “average” dose 300 mg daily

– lower dose if renal/hepatic insufficiency

– higher dose in non-responders• prophylactic colchicine until allopurinol dose

stable

URATE LOWERING DRUGS

Allopurinol side effects• pruritic papular rash 3-10%

consider desensitization protocol

• GI upset, macular or vasculitic or TEN skin rash, myelo-suppression, hepatitis, alopecia

• Allopurinol Hypersensitivity (AHS): skin rash, fever, hepatitis, eosinophilia, renal impairment

URATE LOWERING DRUGS

Allopurinol drug interactions

–Coumadin–Vidarabine–Cyclosporin–Azothiaprine

allopurinol may prolong ½ life of these drugs and increase toxicity

GOUT -PROPHYLAXIS

Colchicine (at low dose)

• indications: -until dose of urate lowering drug optimized

-if patient cannot take a urate lowering drug• dose:

-0.6 mg qd or occasional b.i.d. -0.3 mg qd or q2days if renal disease or elderly

SMALLEST DAILY DOSE POSSIBLE INDIVIDUALIZE

URATE LOWERING DRUGS

The Future:1. fuboxistat NEJM 2005; 353:2450

- more selective non-purine xanthine oxidase inhibitor - mainly metabolized in liver - more info needed about short and long term safety2. natural uricase - issues with toxicity- Ab formation, anaphylaxis, fever3. uricase with HMW polyethylene glycol PEG4. ? new treatment targeting URAT1 anion exchange