OPTIMIZING CURRENT

TREATMENT OF GOUT

Rees F, et al.
National Reviews Rheumatology 10, 2014

GOUT

Gout common form of inflammatory arthritis.

:

Prevalence <> Age

Chronic elevation uric acid (UA) lvl saturation point monosodium urate crystals

Urate crystals superf. articular cartilage, subchondral bone, fibro peri articular
tissue

OR as subcutaneous tophi

Prevalence:

Acute attack treated irreversible joint damage

Also: High serum UA risk of CV disease, stroke, & CKD

Tx strategies Audited tx for gout in primary & hospital optimal

This journal reviews EULAR & BSR guidelines (2006&2007) and ACR guidelines
(2012)

Fig 1. Metabolism of UA & risk factors for gout

Management of Acute Gout

As soon as Possible:

Initial diagnosis

Known gout

1st warning symptoms

NSAIDs

Commonly used

At maximum dose, rather than titrated

Some doctors indomethacin

PPI is recommended BUT risk for small & large bowel risk altered

COX-2 inhibitor lower incidence GI event

Colchicine

1s line tx

Less expensive than other biologic agents (etc. IL-1 inhibition agent)

Low dose regiment (1.8 mg total over 1 hour) effective

But high dose (4.8 mg total over 6 hour) GI disturbance (nausea, vomiting, or diarrhea)

EULAR max: 0.5 mg colchicine tid

ACR loading dose colchicine 1.2 mg, than 0.6 mg od or bid

Moderate-Severe CKD 0.5 mg od or bid

Europe-modified dose 1.0 mg loading, 1 hr later 0.5 mg 1st day. 2nd day etc 0.5 mg 24 times/day

Low 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 recommended

Corticosteroid

Intra Articular

Ideal aspiration + inj corticosteroid in hospital setting

When colchicine, NSAIDs, or Corticosteroid oral contraindicated

Difficuly gout attack is polyarticular / midfood / no physician w/ sufficient exp.

But no guideline for optimal dosage

Corticosteroid

Oral

Prednisolone used when NSAIDs are contraindicated / failed

No guide for optimal dosage

One 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 1 st day
50 mg indomethacin tid for 2 day 25 mg tid for 3 days.

Intramuscular

Single injection, but no consensus on dose.

Trial: 60 mg im triamcinolone acetonide = oral indomethacin 50 mg tid for acute gout

High dose 120 mg triamcinolone OR methylprednisolone acute flare of RA / arthropati

painful infflamation. use for acute gout

Biologic agents

Rare When other treatment contraindicated

Anankira, canakinumab, rilonacept has no comparator / compared to suboptimal

dose of triamcinolone.

Adventages: modest but very expensive, largely unlicensed. Canakinumab

Europe, UK / USA

Physical Treatment

Standard treatment + Ice therapy locally

Improvement greater in 1 week.

Simple & safe

No RCT.

ISSUES

NSAIDs 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 Management

NSAIDs 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,nonlosartan Angiotensin II receptor Blocker SUA. Losartan & CCB SUA

Comorbid (hpt, hyperlipidaemia, & hyperglycaemia need to be managed optimally.

Urate Lowering Therapy

Fully 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
nephrolithiasis

Studies 2011 and 2012 shown crystal deposition in asymptomatic hyperuricaemia.

Dual-energy CT crystal deposition in distal patellar tendon.

Trend earlier commencement of ULT

Delaying 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 Inhibitor

1st choice ULT.

Allupurinol favoured cost consideration & long-term safety

Allupurinol

Purine 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 <= 360 umol/l (> 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 <300 umol/l (5 mg/dl).

Dose adjustment 50 mg in renal impairment inconclusive.

Well tolerated 8-9 pt out of 10 pts

Intolerance: nausea, GI disturbance, headache / rash

Rarely drug reaction / ras with eosinophilia & systemic sypmtoms (DRESS), severe
cutaneous rx (SCAR TEN & SSJ).

Occur 1st few month. Risk fx renal impairment, concomitant use of diuretic, tx fix
dose 300 mg, presence HLA-B*5801 alel. (Korean, Chinese, Thai Pop).

Beneficial in CV disease & renal disease.

Febuxostat

Non-purin high specific XOI goes hepatic metabolism.

Two RCT efficacy reducing SUA

Double blind RCT superior at doses 80 mg and 120 mg daily.

Adverse event liver function test abn.

Not recommended in heart failure

Free from SCAR & DRESS rx.

No dose-adjustment in renal impairment, but not recommended in eGFR < 30.

Inability to increase dose, CV safety concern, high cost.

Uricosuric drugs

Prevent reuptake uric acid at prox renal tubule, increase uric acid excretion.

Can predispose stone formation has to drink plenty of fluid & well hydrated

Benzbromarone (50-20 mg daily), probenecid (250-500 mg bid) & sulfinpyrazone

(200-800 mg daily).

Inexpensive, but lack of availability.

Effective deducing SUA, readily stepwise dosage increases.

Probenecid & sulfinphyrazone CI: severe renal impairment / nephrolithiasis

Benzbormarone limited because hepatotoxicity, particulary in Asia.

Liver fx should bechecked for 1st few month & dose-adjustment.

Other ULT

Losartan, oral vit C, fenofibrate uricosuric effect.

As adjunctive for coexistent hpt / hyperlipidaemia.

Pegloticase pegylated uricase treatment refractory gout. IV infusion 8 mg / 2

weeks. Rapidly reduced SUA for several weeks.

But risk for anaphylaxis & infusion reaction, so need premed with antihistamin &
corticosteroid.

Caution use in heart failure.

Rasburicase unlicenced for gout & more antigenic than pegloticase.

Other ULT in development RDEA594 (lesinurad), uricosuric. BCX 4208 (ulodesine),

purine nucleoside phosphorylase inh. But not yet licensed

Optimum SUA level

< 360 umol/l (6 mg/dl)

Long history of gout / presence of tophi target < 300 umol/l (5 mg/dl).

Lifelong maintenance SUA very low increase risk neurodegenerative disesase

Parkinson, dementia, multiple sclerosis.

Author suggest < 300 umol/l for 1st 3-5 yrs tx then, if no further attack dose
reduced allowing SUA rise but remain below sat point (300-360 umol/l).

Lifelong therapy at low dose.

Flare Prophylaxis

ULT induced flare. EULAR colchicine (0.5 mg od or bid) or NSAIDs (plus PPI) for 1st
few month of ULT.

Rilonacept & canakinumab has shown efficacy but very expensive & not licenced

Improving the standard of care

Current standart of care suboptimal

Most concentrate in acute attack rather than long-term therapy.

Use allopurinol at fixed dose 300 mg (for most pts is insufficient).

Lead to acute attack & develop joint damage poor adherence to ULT.

Poor adherence predominantly due lact of education.

Healt professional have to appropriate traning best practice management of gout

Thank You