day in the case of CKD. Higher doses can lead to the
risk of adverse reactions. The dosage is gradually
increased by 50 (1/2 cp) or 100mg (1 cp) per month,
and adapted to the uricaemia observed: the aim is
to reach the therapeutic target. Physicians should
avoid clinical or therapeutic inertia, so the dose of
allopurinol is not increased while the sUA target is
not reached. 7 Once found, the allopurinol dosage
is maintained. Clinical follow-up tells the patient
if he/she has had any new gout attacks, and if he/
she has been able to treat them as soon as possible
(‘colchicine in the pocket’). Biological monitoring
is essential: uricaemia and renal function (serum
creatinine and estimation of glomerular filtration
rate according to the MDRD or CKD-EPI formulas).
Monitoring is initially carried out monthly until the
target uricaemia is reached, then semi-annually.
The patient should be informed of possible
adverse events in the first few months of treatment:
a simple rash and pruritus requires the permanent
discontinuation of allopurinol. Re-introduction
could cause serious forms of skin reaction. Very
rarely, severe rashes such as Lyell’s syndrome,
Stevens-Johnson’s syndrome or drug reaction with
eosinophilia and systemic symptoms (DRESS) are
encountered. DRESS is a generalised rash with
blood eosinophilia, and haematological, renal and
hepatic damage, which is regularly fatal. The factors
favouring DRESS are an initial dose of allopurinol
that is too high, Asian or African origin (HLA B58*01
gene with a high risk of DRESS to allopurinol), and
CKD.
Febuxostat is more expensive than allopurinol
but generics will soon be available. It is available
in Europe as 80 and 120mg tablets – not breakable,
which does not allow for titration of dose as easily.
Febuxostat can be used in CKD 3.
Febuxostat is effective in lowering uricaemia
within a few weeks; however, the rapid decrease
will lead to regular gout attacks at the beginning
of treatment. It is therefore essential to gradually
increase the dose by cutting the tablets or by
giving only alternate doses in one-month
increment (80mg twice a week for one month,
then 80mg three times a week, and finally, every
other day). Its use should be discussed in cases of
unstable coronary insufficiency or heart failure
because its cardiovascular safety is still under
evaluation.
White blood cell count, transaminases and
thyroid-stimulating hormone should be monitored
in addition to uricaemia and estimated glomerular
filtration rate (eGFR) as for allopurinol.
Uricosurics
The available uricosurics were probenecid and
benzbromarone and, more recently, a third drug
(lesinurad) is now available in Europe after quality
clinical studies. All are antagonists of uric acid
transporters through the cells of the renal tubule.
Probenecid requires twice-daily dosing. There
is a risk of lithiasis due to its uricosuric effect. It
interacts with other drugs, which can also limit its
use.
Benzbromarone is quickly effective but its use
also carries a risk of lithiasis (the risk can be reduced
by adequate fluid intake and alkalinisation of the
urine).
Lesinurad (200mg) is used in combination with
an XOI, if the uricaemia is not sufficiently lowered,
for example, through allopurinol at doses of 200 or
300mg/day. Lesinurad is well tolerated, but transient
increases in serum creatinine can be observed. The
risk of lithiasis is decreased because urinary uric
Table 2
Six key indicators for gout management 1
Treat to target Goal to reduce sUA level below 6.0, or even 5.0mg/dl
Start low, go slow Start allopurinol at 100mg daily, increase by 50 or
100mg every month (for convenience) because there is
no reason to reduce sUA level abruptly
‘Chi va piano va sano’ The start low and go slow approach reduces flares and
helps avoid skin rashes or DRESS
Tight control Increase allopurinol steadily up to optimal dosage to
achieve sUA target
Avoid clinical inertia Do not hesitate/do not be afraid to increase allopurinol
dosage and switch to febuxostat and/or add uricosurics
where appropriate. Treat to target always and always up
to tophi resolution
Monitor regularly Check sUA level and eGFR every six months when
target is achieved. Use for patient adherence
*According to ACR and EULAR, 6.0mg/dl is the sUA target (whereas 5.0mg/dl
is the new 2017 British Society for Rheumatology target) for all patients
starting treatment.
acid excretion is already reduced through the use of
allopurinol.
Table 2 shows six key indicators for the
management of gout.
What difficulties are encountered with
gout patients?
It has been established that, as with all chronic
diseases, compliance can be poor and up to 50% of
patients no longer take their ULT after one year. This
poor compliance is more pronounced in younger
patients, and pharmacists, nurses and especially the
attending physician or rheumatologist should be
involved in attempting to improve compliance.
Patients (and their families/carers) should be fully
informed and educated about their condition and
medication. 8 Gout is fairly simple to understand
and explain: it is a genetic disease that is caused by
the accumulation of urate crystals due to a failure
to eliminate excess uric acid in the urine. The
kidney and intestine are the two organs involved
in this process. Urate crystals give rise to acute
inflammatory attacks.
The importance of dietary modifications should
be explained. Sweetened carbonated drinks and
beers and strong alcohols are discouraged or even
prohibited; caloric and protein intake from meat
and animal products should be reduced. 6
It should be explained that continuous
hypouricaemic treatment (which reduces uric acid)
is key: the crystals will gradually disappear and so
will the painful attacks. Attacks are possible at the
beginning of treatment by crystal release and these
can be avoided by taking colchicine daily for six
months (prophylaxis).
There are a number of ways of helping to improve
compliance such as daily cellphone messages,
dedicated and trained nurses who regularly contact
or receive regular calls from the patient, therapeutic
education workshops, and pharmacy-based
monitoring. In a controlled trial of dedicated nurses
versus general practitioners, nurse-led interventions
led to better outcomes in gout patients than with
general practitioners. 8,9
References
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