Optimizing current treatment of gout

OPTIMIZING CURRENT TREATMENT OF GOUTRees F, et al.National Reviews Rheumatology 10, 2014

1GOUTGout common form of inflammatory arthritis. Prevalence Age Chronic elevation uric acid (UA) lvl saturation point monosodium urate crystalsUrate crystals superf. articular cartilage, subchondral bone, fibro peri articular tissueOR as subcutaneous tophi Prevalence:

:Mengapa prevalensi meningkat seiring usia?

2Acute attack treated irreversible joint damageAlso: High serum UA risk of CV disease, stroke, & CKD

Tx strategies Audited tx for gout in primary & hospital optimalThis journal reviews EULAR & BSR guidelines (2006&2007) and ACR guidelines (2012)Fig 1. Metabolism of UA & risk factors for gout

Management of Acute GoutAs soon as Possible:Initial diagnosisKnown gout1st warning symptomsNSAIDsCommonly usedAt maximum dose, rather than titratedSome doctors indomethacinPPI is recommended BUT risk for small & large bowel risk alteredCOX-2 inhibitor lower incidence GI event1s line txLess expensive than other biologic agents (etc. IL-1 inhibition agent)Low dose regiment (1.8 mg total over 1 hour) effectiveBut high dose (4.8 mg total over 6 hour) GI disturbance (nausea, vomiting, or diarrhea)ColchicineEULAR max: 0.5 mg colchicine tidACR loading dose colchicine 1.2 mg, than 0.6 mg od or bidModerate-Severe CKD 0.5 mg od or bidEurope-modified dose 1.0 mg loading, 1 hr later 0.5 mg 1st day. 2nd day etc 0.5 mg 2-4 times/dayLow dose colchicine: Pts using P450 3A4 inhibitor ciclosporin, ketoconazole, ritonavir, clarithromycin, erythromycin, ext-release verapamil, ext-release diltiazem.People with renal impairment, statin stop temporarily.IV Colchicine high toxic & not recommendedCorticosteroidIntra ArticularIdeal aspiration + inj corticosteroid in hospital settingWhen colchicine, NSAIDs, or Corticosteroid oral contraindicatedDifficuly gout attack is polyarticular / midfood / no physician w/ sufficient exp.But no guideline for optimal dosageCorticosteroidOralPrednisolone used when NSAIDs are contraindicated / failedNo guide for optimal dosageOne trial: prednisolone 35 mg = oral naproxen 500 mg bid.Another trial: 30 mg prednisolone daily for 6 days = im diclofenac 75 mg + 50 mg indomethacin oral 1st day 50 mg indomethacin tid for 2 day 25 mg tid for 3 days.IntramuscularSingle injection, but no consensus on dose.Trial: 60 mg im triamcinolone acetonide = oral indomethacin 50 mg tid for acute goutHigh dose 120 mg triamcinolone OR methylprednisolone acute flare of RA / arthropati painful infflamation. use for acute goutBiologic agentsRare When other treatment contraindicatedAnankira, canakinumab, rilonacept has no comparator / compared to suboptimal dose of triamcinolone.Adventages: modest but very expensive, largely unlicensed. Canakinumab Europe, UK / USAPhysical TreatmentStandard treatment + Ice therapy locallyImprovement greater in 1 week.Simple & safeNo RCT.ISSUESNSAIDs readily available but CI with age, comorbidity, concomitant drug, or renal impairment.When expertise available joint asp & inj corticosteroid (safe).Successful management treat individually, discussing, start early as posibble, can be combined (ia corticosteroid + colchicine oral)Long-Term ManagementNSAIDs readily available but CI with age, comorbidity, concomitant drug, or renal impairment.When expertise available joint asp & inj corticosteroid (safe).Successful management treat individually, discussing, start early as posibble, can be combined (ia corticosteroid + colchicine oral)Paradox acute attack + rapid decrease in uric acid lvls.Daily intake skimmed milk powder + glycomacropeptide & G600 reduces frequency acue attack.Other risk factor chronic diuretic therapy for hypertension (B-Blocker,ACEI,non-losartan Angiotensin II receptor Blocker SUA. Losartan & CCB SUAComorbid (hpt, hyperlipidaemia, & hyperglycaemia need to be managed optimally.Urate Lowering TherapyFully explained to pts & titrated upwardly.The lower the SUA, the faster the dissolution of crystal & red size of tophi.Still risk for acute attack until all crystals dissolved.Indication for ULT reccurent attack, clinically detectable tophi, joint damage or nephrolithiasisStudies 2011 and 2012 shown crystal deposition in asymptomatic hyperuricaemia.Dual-energy CT crystal deposition in distal patellar tendon.Trend earlier commencement of ULTDelaying ULT until acute attack commencing ULT will prolong attace / precipitate polyarticular flare. But one RCT no difference in pain or flare rate.Many GP logistical advantage initiating ULT for acute attack.Xantin Oxidase Inhibitor1st choice ULT.Allupurinol favoured cost consideration & long-term safetyAllupurinolPurine analog & nonspecific inhibitor xanthine oxidase.Oxypurinol active metabolite excreted via kidney.NO RCT placebo controlled.Study (2013, UK) M median dose to reach target SUA 90% participant) is 400 mg od.1960 300 mg suboptimal.USA, 2005 300 mg target only 20% pts.Initial dosage recommended 100 mg. Increase 100 mg / month. Stop if SUA < 360 umol (6 mg/dl) or