This document summarizes the evolution of guidelines for managing gout. It discusses recommendations for treating acute gout attacks, initiating urate-lowering therapies, treating to target serum urate levels, and providing prophylaxis when starting urate-lowering drugs to prevent acute attacks. The guidelines have increasingly recommended treating to a target serum urate level of less than 6 mg/dL, initiating urate-lowering therapies earlier based on attack frequency or severity factors, and providing longer-term prophylaxis when starting urate-lowering drugs.

1. Gout Management Evolution
Mohamed Ahmed Hefny, MD.

2. To know, is to know that you know
nothing. That is the meaning of true
knowledge.
“Socrates”

3. Acute Gout Therapies
• For treatment of acute gout initiative recommend NSAIDs,
corticosteroids or oral colchicine to be similarly effective.
• Recommended oral colchicine and/or NSAID as first-line agents over
corticosteroids forthe treatment of acute attacks.
• When selecting colchicine, all guidelines recommend using low-dose
colchicine (1.8–2.0mg, country-specific loading dose).
• The ACR recommended topical ice application to be an appropriate
adjunctive measure to one or more pharmacologic therapies for
acute gouty arthritis.

4. • Patients with severe disease (defined as >7 of 10 pain on a 0–10 VAS
and/or acute polyarticular gout attack, or an attack involving at least
one to two large joints), the ACR guidelines recommend initiating
combination pharmacologic therapy and use of IL-1 inhibition in
individuals with refractory attacks of acute gout or contraindications
to all the three agents above.
• BSR, EULAR, and ACR all recommend combining pharmacological and
nonpharmacological treatments such as rest or ice as add-on to single-
drug treatment (monotherapy) for acute gouty episodes.
• ACR and BSR also recommend initiating therapy as close to onset of
attack (within 24 h of onset).

8. Urate-lowering Therapies
• Frequency of attacks has been considered an indication for ULT in all
guidelines, beginning with more than three attacks per year in the 2002
Dutch guidelines, decreasing to two attacks per year in the 2007 British
guidelines and supported thereafter.
• Presence of tophi has been supported throughout all iterations of gout
guidelines, as has urate nephrolithiasis.
• Radiographic changes (of gout) have been recommended by both
EULAR and ACR.
• Gouty arthropathy, as its own entity, has been described as an indication
for ULT in 2006 EULAR, the 2014 update and the 3e initiative.

9. • Comorbidities began to be considered indications for ULT with chronic
kidney disease (CKD) beginning as early as 2007. The British guidelines
included use of diuretics. (Most other guidelines recommend eliminating
diuretics where possible).
• The proposed 2014 EULAR update expanded this list to include
hypertension, ischemic heart disease and heart failure.
• For the first time, the proposed 2014 EULAR update also includes patient
characteristics associated with poor outcomes such as young age at first
attack (age <40 years) and very high sUA (>8.0 mg/dl; 480 mmol/l).

10. • Since the introduction of Febuxostat, with the exception of the
ACR, all guidelines recommended allopurinol as first line with
Febuxostat or Uricosuric as second line.
• The ACR recommended allopurinol or Febuxostat as first line with
the caveat that cost considerations were not included in this
recommendation.
• However, uricosourics, such as probenecid, recommended as an
alternative first line agent by ACR, could be used as alternative first
line in case of normal kidney function.
• All recent guidelines supported the use of combination (e.g.
xanthine oxidase inhibitors and uricosourics) if monotherapy was
not effective.

11. • All guidelines have agreed that serum target should be at least < 6mg/dl
for all patients on ULT.
• The BSR recommends less than 5mg/dl for all patients. The ACR and
subsequent guidelines recommended less than 6mg/dl for all gout
patients and less than 5mg/dl for patients with severe gout defined.
• The 2014 EULAR update defined severe gout as patients with tophi,
chronic arthropathy or frequent attacks.
• The EULAR 2014 update added the recommendation that sUA should not
be suppressed less than 3mg/dl for the ‘long term’.

12. • The majority of the guidelines suggest starting allopurinol (in patients
with normal renal function) at 100mg/day and then titrating up by
100mg increments every 2–4 weeks until the target sUA has been
reached.
• Many of the guidelines noted that doses in excess of 300mg are
frequently needed. For patients with renal dysfunction,
recommendations varied but all agreed with lower starting doses and
more cautious titration.
• The ACR guidelines introduced the importance of pharmaco-genetic
screening (HLA-B5801) in select patients as these select groups of
patients are at markedly increased risk for severe allopurinol
hypersensitivity syndrome due to the high frequency of the risk allele
HLA-B5801.

13. • Since the introduction of pegloticase, guidelines have recommended
that its use be reserved for patients who are refractory (or
contraindicated) to all other agents.
• The major issues that limit the use of this agent lie in its strong
immunogenic potential for antibody production, thus infusion
reactions, and significant costs.
• The ACR guidelines included restrictions for patients with persistent
attacks (at least seven per year in nontophaceous patients or at least
two per year in tophaceous patients) or chronic tophaceous gouty
arthropathy.
• The EULAR update restricted pegloticase to ‘crystal-proven, severe
debilitating chronic tophaceous gout and poor quality of life, in whom
the sUA target cannot be reached with any other available drug at the
maximal dosage including combinations’.

15. Prophylaxis Against Acute Gout Attacks When Starting Urate lowering Therapies
Evolution of concurrent prophylaxis against acute gout attacks with ULT initiation has
evolved over the years.
• The 2002 Dutch guidelines recommended against chronic colchicines as well.
• Beginning with EULAR, colchicine or NSAIDs were recommended for the first few
months.
• The British guidelines extended colchicine for 6 months (limiting low-dose NSAIDs
to 6 weeks).
• The ACR guidelines increased duration regardless of agent (colchicine, low-dose
NSAID or low-dose steroid) to 6 months or at least 3 months beyond achieving
sUA for nontophaceous patients.
• The 3e supported prophylaxis but was unresolved about duration.
The updated EULAR guidelines recommended 6 months.

17. Thank You