Gout Management Evolution

Mohamed Ahmed Hefny, MD.

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

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.

• 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).

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.

• 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).

• 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.

• 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’.

• 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.

• 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’.

Prophylaxis Against Acute Gout Attacks When Starting Urate lowering TherapiesEvolution 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.

Thank You