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
