Transcript Diapositiva 1

Difficult gout.
Gout in the elderly
and drug-induced gout
1
Increasing prevalence of gout and
hyperuricaemia among elderly subjects
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Wallace KL, et al. J Rheumatol 2004;31:1582-1587.
Annual gout prevalence stratified by age
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Wallace KL, et al. J Rheumatol 2004;31:1582-1587.
UK prevalence of gout
>75 years
Overall
1.4%
Men: 7.3%
Women: 2.8%
M
F
M
F
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Mikuls, et al. Ann Rheum Dis 2005;64:267-272.
Perception of disease and health-related
quality of life in elderly patients with gout
SF-36: Physical Component Summary (PCS) and Mental Component Summary (MCS)
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Lee SJ. Rheumatology 2009;48:582-586.
Clinical features of gout in the elderly
• Increased prevalence
• Women more frequently affected
• Small joints of the fingers more
frequently involved
• Polyarticular onset more common
• Tophi occur earlier in the course
of gout, often in atypical locations
• Frequently associated with other
joint diseases (OA, CPPD)
• Comorbidities more common
• Increased association with
diuretic use
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By kind permission of L. Punzi, Rheumatology Unit,
University of Padua
Wise CM. Rheum Dis Clin N Am 2007;33:33-55.
De Leonardis F, et al. Rheumatol Int 2007;28:1-7.
Increased association with diuretic use
• A high association with diuretic use and renal insufficiency has been noted
in most elderly populations with gout
• Diuretic use has been reported in more than 75% of patients who have
elderly onset gout, with a frequency of 95% to 100% in women
• Most small series of elderly patients who have atypical finger joint disease or
tophaceous deposits report a consistent majority of patients taking diuretics
• A retrospective cohort study documented an almost two-fold increase in the
risk of initiation of anti-gout therapy in patients within 2 years of starting
thiazide diuretics for hypertension compared to patients given non-thiazide
therapy
• Because of a lack of direct comparison to other elderly patients, it is unclear
whether a decrease in renal function is peculiar to patients who have gout or
merely reflects the trend seen in elderly populations in general
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Scott JT, Higgins CS. Ann Rheum Dis 1992;51:259-261.
Fam AG, et al. J Rheumatol 1996;23:684-689.
Gurwitz JH, et al. J Clin Epidemiol 1997;50:953-959.
Janssens HJ, et al. Ann Rheum Dis 2006;65:1080-1083.
Healthcare utilisation
in older adults with gout
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Hanly JG, et al. J Rheumatol 2009;36:822-830.
Total all-cause health care costs
among gout patients
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Wu EQ, et al. J Manag Care Pharm 2008;14(2):164-175.
Reasons why gouty patients present
at an emergency department
•
•
•
•
•
•
Severity of the acute attack
Attack during the night
Elderly age
Comorbidity
Polypharmacy
Flares after the introduction
of urate-lowering therapy
By kind permission of L. Punzi,
Rheumatology Unit,
University of Padua
10
Wise CM. Rheum Dis Clin N Am 2007;33:33-55.
De Leonardis F, et al. Rheumatol Int 2007;28:1-7.
Management of gout in the elderly:
general aspects
• Atypical presentation may make diagnosis difficult and hence may delay
initiation of treatment
• Colchicine is less effective
• Use of NSAIDs or colchicine is limited by their side-effect profile
• Use of uricosuric agents may be limited due to the presence of co-morbidities
including renal disease
• Restricting diet to eliminate purine-rich food is often challenging, and is of
limited benefit
• Drug interactions are more likely, as polypharmacy is common
• Social, economic, and cognitive factors can affect compliance with
medications and with laboratory monitoring
• Trials on newer therapies often do not include elderly subjects
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Singh H, Torralba HB. Geriatrics 2008;63(7):13-8,20.
Management of acute gout attacks
in the elderly: the colchicine dilemma
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Morris I, et al. BMJ 2003;327:1275-1276.
Colchicine in acute gout
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Morris I, et al. BMJ 2003;327:1275-1276.
Incidence of adverse events according
to colchicine dose
Colchicine dose
High (n=52)
Low (n=74)
Placebo (n=59)
40 (76.9)
27 (36.5)
16 (27.1)
Gastrointestinal adverse events
40 (76.9)
19 (25.7)
12 (20.3)
Diarrhoea (all occurences)
40 (76.9)
17 (23.0)
8 (13.6)
Nausea (all occurences)
9 (17.3)
3 (4.1)
3 (5.1)
Vomiting (all occurences)
9 (17.3)
0 (0)
0 (0)
10 (19.2)
0 (0)
1 (1.7)
Diarrhoea (only severe intensity)
10 (19.2)
0 (0)
0 (0)
Melena (only severe intensity)
1 (1.92)
0 (0)
0 (0)
Nausea (only severe intensity)
1 (1.92)
0 (0)
0 (0)
0 (0)
0 (0)
1 (1.7)
0 (0)
0 (0)
0 (0)
Adverse events
Severe intensity adverse events
Gout (only severe intensity)
Serious adverse events
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Terkeltaub R, et al. Arthritis & Rheumatism 2010;62:1060-1068.
Management of chronic gout in the
elderly: focus on allopurinol
EULAR recommendations 2006
for the management of gout
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Allopurinol is an appropriate long-term urate lowering therapy.
It should be started at low doses (e.g. 100 mg daily) and
increased by 100 mg every 2-4 weeks if required. The dose
should be adjusted in those 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).
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Zhang W, et al. Ann Rheum Dis 2006;65:1312-1324.
Management of chronic gout in the
elderly: allopurinol toxicity
• Minor self-limiting drug reactions are relatively common, being
estimated to occur in up to 10% of patients, and include itching,
rash and gastrointestinal problems
• The more serious, indeed potentially fatal, allopurinol
hypersensitivity syndrome (ASH) is far less common, being
estimated to occur in 0.4% of patients
• ASH includes features such as eosinophilia, liver and renal
dysfunction, vasculitis, bone marrow suppression and rash
• Known risk factors for developing AHS include renal impairment,
older age, comorbidities, use of thiazide diuretics and a genetic
predisposition
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Kumar A, et al. Br Med J 1996;312:173-4.
Fam AG, et al. Arthritis Rheum 2001;44:231-8.
Rider TG, Jordan KM. Rheumatology 2010;49:5-14.
Clinical use of febuxostat
No dose adjustment needed in:
• Elderly
• Mild to moderate renal function impairment
• Mild to moderate (caution) liver function impairment
No dose adjustment needed while on:
•
•
•
•
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Colchicine, indomethacin, naproxen
Warfarin
Hydrochlorothiazide
CYP 2D6 substrates
SmPC febuxostat.
Special precautions
Febuxostat is not recommended in:
• patients with ischaemic heart disease or congestive heart failure
• patients being treated with mercaptopurine or azathioprine
• patients with severe renal function impairment (no experience)
• patients with moderate or severe liver impairment
Caution is required when febuxostat is used in:
• patients being treated with theophylline
• patients with thyroid disorders
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SmPC febuxostat.
Summary of the management
of gout in the elderly
Treatment options
Notes
Acute attacks
Colchicine (oral)
At low doses (0.5-1 mg/day) colchicine is safe also in the elderly. Adminster with caution in concomitance with
strong inhibitors of p-glycoprotein and cytochrome P450, such as clarithromycin, erythromycin or cyclosporine
NSAIDs
With caution, NSAIDs should be taken at low doses, for limited periods, and by patients with normal renal
function; consider a COX-2 inhibitor or adding a gastroprotective agent to reduce gastrointestinal toxicity to
avoid in patients treated with anticoagulants
Corticosteroids
articular, oral, parenteral)
(intra-
Corticotropin (ACTH) (parenteral)
Preferable in patients who have comorbid conditions, with caution in diabetes
Similar to corticosteroids, availability limited to some patients
Short-term prophylaxis
Colchicine
Safe at low doses
NSAIDs
See above
Urate-lowering therapy
Uricosuric agents
Seldom effective in elderly patients because of renal dysfunction
Allopurinol
Reduce dosage based on creatinine clearance, titrate dose
Febuxostat
Better tolerated than allopurinol in the elderly. May be considered in mild to moderate renal impairment
(creat. clear. 20-60 ml/min) and/or non-alcoholic hepatic impairment
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Zhang W, et al. Ann Rheum Dis 2006;65:1301-1311.
Richette P, et al. Lancet 2010;375:318-328.
Terkeltaub R. Nature Rev Rheumatol 2010:6:30-38.
Drug-induced gout
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Drugs potentially inducing hyperuricaemia
by a reduction of renal excretion
Cyclosporine
Alcohol
Nicotinic acid
Thiazides
Lasix (furosemide) or other loop diuretics
Ethambutol
Aspirin (low dose)
Pyrazinamide
Andrew JK, et al. Am J Manag Care 2005;11:S435-S442.
Underwood M. BMJ 2006;332:1315-9.
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Frequent causes of decreased renal
excretion of urate in the elderly
• Drugs
–
–
–
–
–
Thiazides
Loop diuretics
Aspirin (low-dose)
Ethanol
Levodopa
• Renal
– Hypertension
– Chronic renal failure (any aetiology)
• Metabolic/endocrine
–
–
–
–
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Obesity
Hypothyroidism
Hyperparathyroidism
Dehydration
Wise CM. Rheum Dis Clin N Am 2007;33:33-55.
Perez-Ruiz F. Rheumatology 2009;48:ii9-ii14.
Cyclosporine and tacrolimus
• Calcineurin inhibitors
– Both drugs can impair renal uric acid excretion
– High sUA/decreased UA excretion (reduced fractional
excretion)
– Mg leakage via tubular dysfunction (high fractional
excretion)
• Gout in organ transplant recipients
– Heart and kidney tranplantation: higher sUA/MSU deposits
along with ageing, chronic kidney disease, diuretics
– Liver transplantation: 10-50% hyperuricaemia; low gout
prevalence (2.6-6%)
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Perez-Ruiz F, et al. Transplantation 2001;71:696-698.
Shibolet O, et al. Transplantation 2004;77:1576-1580.
Fernández-Molina G, et al. Transplantation 2008;86:1543-1547.
Anti-tuberculous drugs
and hyperuricaemia
• Pyrazinamide
– Hyperuricaemic effect due to modulation of urate
transport via the proximal tubules
– Quickly reversible after the drug is stopped
• Ethambutol
– Effect not dependent on the dose
– Reversible within 15 days after the drug is stopped
• Rifampicin
– Seen less frequently
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Merriman TR, et al. Joint Bone Spine 2011;78:35-40.