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

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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:

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 sepsis e.g.,) depomedrol mg with lidocaine 2.oral prednisone 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

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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 URAT1 1. 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

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URATE LOWERING DRUGS Allopurinol - an inhibitor of xanthine oxidase start low eg) mg qd increase by mg 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 mg qd or q2days if renal disease or elderly SMALLEST DAILY DOSE POSSIBLE INDIVIDUALIZE

URATE LOWERING DRUGS The Future: 1. fuboxistat NEJM 2005; 353: more selective non-purine xanthine oxidase inhibitor - mainly metabolized in liver - more info needed about short and long term safety 2. natural uricase - issues with toxicity- Ab formation, anaphylaxis, fever 3. uricase with HMW polyethylene glycol PEG 4. ? new treatment targeting URAT1 anion exchange