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Gout management:
general aspects and
treatment of acute gout
1
• Gout is the most frequent inflammatory
arthritis in men and its prevalence is rising in
the population, including among postmenopausal women
• Gout is a severe disease, characterised by
an intense acute inflammatory reaction and
a chronic evolution associated with bone
erosions and soft-tissue deposits (tophi)
• Gout may be considered a systemic disease,
since it may induce severe nephropathy and
increase cardiovascular risk
• Gout is a curable disease!
Richette P, et al. Lancet 2010;375:318-328.
So A, et al. Arthritis Res Ther 2008;10:221.
Feig DI, et al. N Engl J Med 2008;359(17):1811-1821.
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• Treatment adherence seems to be poorer in
patients with gout than in those with many
other chronic diseases
• Adherence is particularly poor with regard to
urate-lowering therapy in relatively young
patients and reflects not only the behaviour
patterns of patients with gout, but also
systematic deficiencies in the education of
these patients which need to be rectified
Briesacher BA et al. Pharmacotherapy 2008;28:437-443
Harrold LR et al. Arthritis Res. Ther. 2009;11,R46
Terkeltaub R. Nat Rev Rheumatol 2010;6:30-38
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By kind permission of L. Punzi,
Rheumatology Unit, University of Padua
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Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
EULAR recommendations 2006
for the management of gout
1.
Optimal treatment of gout requires both non-pharmacological and pharmacological modalities and should be tailored according to:
a. specific risk factors (levels of serum acid uric, previous attacks, radiographic signs)
b. clinical phase (acute/recurrent gout, intercritical gout, and chronic tophaceous gout)
c. general risk factors (age,sex,obesity,alcohol consumption,urate raising drugs,drug interactions, comorbidity)
2.
Patient education and appropriate lifestyle advice regarding weight loss if obese, diet, and reduced alcohol (especially beer) are core aspects of
management.
3.
Associated co-morbidity and risk factors such as hyperlipidaemia, hypertension, hyperglycaemia, obesity and smoking should be addressed as an
important part of the management of gout.
4.
Oral colchicine and/or NSAID are first line agents for systemic treatment acute attacks; in the absence of contraindications, an NSAID is a
convenient and well accepted option
5.
High doses of colchicine lead to side effects and low doses (for example 0.5 mg three times daily) may be sufficient for some patients with acute
gout
6.
Intra-articular aspiration and injection of long acting steroid is an effective and safe treatment for an acute attack
7.
Urate lowering therapy is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout
8.
The therapeutic goal of urate lowering therapy is to promote crystals dissolution and prevent crystal formation; this is achieved by maintaining the
serum uric acid below the saturation point for monosodium urate (≤360 μmol/l)
9.
Allopurinol is an appropriate long-term urate lowering drug; it should be started at a low dose (for example 100mg daily), and increased by 100mg
every 2-4 weeks if required; the dose should be adjusted in patients with renal impairment; if allopurinol toxicity occurs, options include other
xanthine oxidase inhibitors, a uricosuric agent, or allopurinol desensitisation (the latter only in cases of mild rash)
10.
Uricosuric agents such as probenecid and sulphinpyrazone can be used as an alternative to allopurinol in patients with normal renal function but
are relatively contra-indicated in patients with urolithiasis; benzbromarone can be used in patients with mild to moderate renal insufficiency on a
named patient basis but carries a small risk of hepatotoxicity
11.
Prophylaxis against acute attacks during the first months of urate lowering therapy can be achieved by colchicines (0.5 – 1mg daily) and/or an
NSAID (with gastro-protection if indicated).
12.
When gout associates with diuretic therapy, stop the diuretic if possible; for hypertension and hypelipidemia consider use of losartan and
fenofibrate, respectively (both have modest uricosuric effects)
Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
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EULAR recommendations 2006
for the management of gout
1
Optimal treatment of gout requires both non pharmacological
and pharmacological modalities and should be tailored
according to:
a. specific risk factors (levels of serum urate, previous
attacks, radiographic signs)
b. clinical phase (acute/recurrent gout, intercritical gout, and
chronic tophaceous gout)
c. general risk factors (age, gender, obesity, alcohol
consumption, urate elevating drugs, drug interactions and
comorbidity)
Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
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EULAR recommendations 2006
for the management of gout
2
Patient education and appropriate lifestyle advice
regarding weight loss if obese, diet and reduced alcohol
(especially beer) are a core aspect of management.
Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
7
Future research agenda
for gout management
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The efficacy of educational programmes
for lifestyle modification (weight loss,
reduced alcohol intake, restriction of dietary purines)
in patients with gout needs to be assessed.
Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
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Educational programmes
(for both physicians and patients)
• Practitioners need to assess serum urate levels frequently
in individuals at risk for gout, and during monitoring of
ongoing therapy in patients with established gout, both to
ensure that treatment targets are achieved and to assess
the patient’s adherence to therapy
• Education of patients with gout will be critical for the
improvement in treatment adherence
Wall GC, et al. Rheumatol Int 2010;30:749-753.
Harrold LR, et al. Arthritis Res Ther 2006;11,R46.
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Physician education (I)
• Treatment of chronic gout is often suboptimal and poorly
concordant with EULAR recommendations
• Lifestyle advice is infrequently offered
• Urate-lowering therapy restricted to a minority
• Persistent hyperuricaemia seen in allopurinol non-users
and in many users
• Prophylaxis frequently omitted
• (Patients treated with urate-lowering therapy who do not
have gout)
Roddy E, et al. Ann Rheum Dis 2007;66:1311-1315.
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Physician education (II)
• Results of studies have shown only 30-60% of patients
are still prescribed allopurinol one year after initiation of
therapy
• Many practitioners confuse the management of acute
gout and hyperuricaemia
• Enhanced physicians’ education is also essential for
adequate patients’ education
Roddy E, et al. Ann Rheum Dis 2007;66:1311-1315.
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Key points for patients with gout
•
•
•
•
•
Cause of gout
Curable nature
Targets and practicalities of drug therapy
How to prevent and handle flares
Importance of lifestyle and dietary factors
Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
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Patient education in gout (I)
• Effective management of gout requires the patient to
understand the nature of his underlying disease and the factors
which contribute to it
• Patients with hyperuricemia should be told that they need to be
cautious about what they eat and drink
• Slow weight reduction for overweight patients and avoidance of
beer, spirits, fructose-containing soft drink, and consumption of
red meat and seafood
• Patients (and physicians) need to know that they can manage
acute attacks with colchicine or non-steroidal anti-inflammatory
drugs, because early initiation of therapy increases
effectiveness and speed of therapeutic response
Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
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Patient education in gout (II)
• Patients with recurrent gout taking allopurinol or other uratelowering agents, also need to be aware that they should not
stop use of the drug if they have an acute attack
• Education needs to be provided by the physician and reinforced
by printed or on-line material providing a guide to management
and prevention
• Involvement of family members in gout education may enhance
understanding and compliance
Zhang W et al. Ann Rheum Dis 2006;65:1312-1324.
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Lifestyle
• Several features of western diets (high intake of meat, seafood,
fructose-sweetened beverages and beer) are linked to the
development of gout in middle-aged men, whereas high intake
of low-fat dairy products, coffee and ascorbate are linked to
reduced rates of disease development in the same population
• Dietary purines such as guanosine, which is readily absorbed
from beer, promote uric acid overproduction, as do certain
disorders of increased cell turnover, and (in a small fraction of
patients with gout) identifiable mutations in enzymes involved in
purine metabolism
• In the vast majority of patients with gout hyperuricaemia is
primarily driven by renal uric acid hypoexcretion
Hak AE & Choi HK. Curr Opin Rheumatol 2008;20:179-186.
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In daily practice… a diet must be feasible
To avoid
Beer
Alcohols
Fructose-sweetened beverages
To limit
Meat
Fat fish
Seafood
Game
To encourage
Milk
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Drink water (2L/day)
Weight control and physical exercise
Hak AE & Choi HK. Curr Opin Rheumatol 2008;20:179-186.
EULAR recommendations 2006
for the management of gout
3
Associated co-morbidity and risk factors such as
hyperlipidaemia, hypertension, hyperglycaemia, obesity
and smoking should be adressed as an important part
of the management of gout.
Zhang W, et al. Ann Rheum Dis 2006;65:1312-1324.
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Gout: management of co-morbidities
Hypertension, obesity, diabetes, dyslipidaemia must be
recognised and treated (some treatments lower uricaemia)
Hypertension
• Stop diuretics
Hyperlipidaemia
• Diet
Stop smoking
Diabetes
• Reducing hyperinsulinaemia (weight loss)
decreases uricaemia
Zhang W, et al. Ann Rheum Dis 2006;65:1301-1311.
Richette P, et al. Lancet 2010;375:318-328.
Choi HK. Curr Opin Rheumatol 2010:22:165-172.
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EULAR recommendations 2006
for the management of gout
4
Oral colchicine and/or NSAID are first line agents
for systemic treatment of acute attacks. In the absence
of contraindications an NSAID is a convenient
and well accepted option.
5
High doses of colchicine lead to side effects
and low doses (for example 0.5 mg three times daily)
may be sufficient for some patients with acute gout.
Zhang W, et al. Ann Rheum Dis 2006;65:1312-1324.
19
EULAR recommendations 2006
for the management of gout
Future research agenda
1. The optimal drug (colchicine or NSAID), dose, and duration for
prophylaxis of acute attacks when starting urate lowering treatment, and
whether this should vary in different clinical settings (for example, in the
presence of tophi) needs to be determined.
2. Studies are required to determine the optimal dose and frequency of oral
colchicine for treatment of an acute attack.
Zhang W, et al. Ann Rheum Dis 2006;65:1312-1324.
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Terkeltaub R, et al. Arthritis Rheum 2010;62:1060-1068.
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RCT: colchicine high dose vs low dose
vs placebo
Pain response (>50% reduction) at 24 h
RTC Randomised clinical trials
Terkeltaub R, et al. Arthritis Rheum 2010;62:1060-1068.
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EULAR recommendations 2006
for the management of gout
Future research agenda
1
The optimal drug (colchicine or NSAID), dose,
and duration for prophylaxis of acute attacks
when starting urate lowering treatment, and whether
this should vary in different clinical settings (for example,
in the presence of tophi) needs to be determined.
Zhang W, et al. Ann Rheum Dis 2006;65:1312-1324.
23
Richette P, Bardin T. Lancet 2010;375:318-328.
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Steroids in acute gout
Alloway 1993
Triamcinalone 60 mg im vs
indomethacin 150 mg
Equal efficacy
Man 2007
Indomethacin 150 mg vs
prednisone 30 mg 5 d
Efficacy similar
IMC more side effects
Janssens 2008
Naproxen 500 mg bd vs
prednisone 35 mg od for 5 d
Efficacy similar
naproxen more side effects
Siegel 1994
ACTH 40U vs triamcinolone 60 mg
Equal efficacy
Fernandez 1999
Intra-articular steroid
Effective
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Alloway J Rheumatol 1993;20:111-113. Man Ann Emerg Med 2007;49:670-677.
Janssens Lancet 2008;371:1854-1860. Groff GD. Semin Arthritis Rheum 1990;19:329-336.
Fernandez C. J Rheumatol 1999;26:2285-2286. Siegel LB. J Rheumatol 1994;21:1325-1327.
Werlen D. Rev Rhum 1996;63:248-254.
Anti-IL1 AGENTS
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Martinon F, et al. Nature 2006;440(7081):237-41.
Mechanisms of acute inflammation
induced by urate crystals
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8
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Endothelium
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Pro-inflammatory
mediators release
Neutrophil recruitment
Busso N, Arthritis Res Ther 2010;12(2):206.
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