In afore blog we had discussed about the management of gout. Today we update the information for the management of gout based on the latest (2012) clinical guidelines for the management of gout from American College of Rheumatology.

In this post we will discuss about the urate-lowering therapy (ULT) and chronic gouty arthritis with tophaceous disease detected on physical examination (CTGA/chronic tophaceous gouty arthropathy). Note CTGA is defined as chronic gouty arthritis with tophaceous disease detected on physical examination.

In this latest clinical guideline, patients with gout have been divided into 9 cohorts, as shown in picture below.

Figure 1. Fundamental case scenarios in ACR 2012 guideline for gout

If the diagnosis of gout is obtained and correct, a list of steps should be considered as the principles of management for all gout case scenarios.Gout Case Scenarios

Step 1. Patient education on the disease,  the diet and the life-sytle recommendations.

These recommendations belong to nonpharmacologic ULT. Generally they include:

1.weight loss for obese patients, to achieve BMI that promotes general health;

2.healthy overall diet;

3.smoking cessation;

4.exercise (achieve physical fitness); and

5.stay well hydrated.

Diet and food are categorized into three groups: diet needed to avoid, diet needed to limit, and diet encouraged.

The food must avoid consists of [1] organ meats high in purine content (e.g., sweetbreads, liver, kidney), [2] high fructose corn syrup-sweetened sodas and other beverages or foods, [3] alcohol overuse (defined as more than 2 servings per day for a male and 1 serving per day for a female), and any alcohol use in gout during periods of frequent gout attacks or advanced gout under poor control.

The food must limit consists of [1] sizes of beef, lamb, pork, seafood with high purine content (e.g., sardines, shellfish), [2] naturally sweet fruit juices, table sugar and sweetened beverages and desserts, and [3] table salt including in sauces and gravies.

The food encouraged are low-fat or non-fat dairy products, vegetables.

Step 2. The causes of hyperuricemia must be clear for all gout patients. To obtain this intention cetain medical evaluations of certain agents and comorbidities should be performed if indicated since that certain agents and comorbidities can promote hyperuricemia (either causing underexcretion or overproduction of uric acid). Note it is important to identify medications that elevate serum urate level, under which nonessential medications should be stopped.

If patients excrete more than 800 mg of uric acid in 24 hours while eating a regular diet, they are overexcretors and thus overproducers of uric acid. If the patient excretes less than 600 mg of uric acid per 24-hour period on a purine-free diet or less than 800 mg per 24-hour period on an unrestricted diet, the patient is considered a hypoexcreter (Note that this sentence has been removed from the latest Medscape reference for the management of gout).

It is controversial that whether to perform 24-hour urine uric acid evaluation in gout patients with former or present urolithiasis. The 2012 ACR guildeline recommended screening for uric acid overproduction in patient subsets with gout clinical disease onset before age 25 yrs or a history of urolithiasis. In contrast, the latest Medscape reference said a 24-hour urine test of uric acid excretion need not be performed since the patient clearly will need allopurinol (overproducer).

If [1] unclear etiology of hyperuricemia; [2] refractory signs or symptoms of gout; [3] difficulty in reaching the target serum urate level, particularly with renal impairment and a trial of XOI treatment; [4] multiple and/or serious adverse events from pharmacologic ULT, referring  the patients to a specialist is recommended.

Step 3. Evaluating for gout disease activity and burden. Evaluate gout patients and categorize them into the nine subgroup as shown in figure above. A history and thorough physical examination for symptoms of arthritis and signs needed to be assessed.

Step 4. Pharmacologic ULT should be started if indicated. Indications for pharmacologic ULT are any patient with established diagnosis of gouty arthritis and with:

  • Tophus or tophi by clinical exam or imaging study;
  • Frequent attack of acute gouty arthritis (≥2 attacks per year);
  • CKD stage 2 or worse; and/or
  • Past urolithiasis.

The serum urate target is <6 mg/dL in all gout patients. In some patients such as patients with palpable and visible tophi, lower target of <5 mg/dL may be needed to improve gout signs and symptoms.

In the afore blog pharmacologic ULT generally is contraindicated until the acute attack is controlled (starting therapy to control hyperuricemia during an acute attack may intensify and prolong the attack), unless kidneys are at risk because of unusual uric acid load. Typically, agents lowering uric acid levels should be started a few weeks after the attack has resolved and with the protection of prophylactic colchicine or NSAIDs to prevent another attack.

Not consistent is that the 2012 ACR guideline said pharmacologic ULT could be started during an acute gout attack, provided that effective antiinflammatory management has been instituted.

Inadequate response of acute gout to pharmacologic therapy are defined as: [1].<20% improvement in pain score within 24 hours, or [2].<50% improvement in pain score >= 24 hours after initiating pharmacologic therapy. The pain score are measured by Likert scale or VAS (visual analog scales) [For more information about VAS please visit Pharmacoeconomic Evaluating Methods].

When pharmacologic ULT is initiated, serum urate should be monitored every 2-5 weeks during ULT titration. Once the serum urate target is achieved and maintaned the frequency could be prolonged to every 6 months.

Same with the former blog about gout management. Pharmacologic ULT are based on three different classes of medicatons: xanthine oxidase inhibitors, uricosuric agents, and pegloticase.

About The Strategy for Pharmacologic ULT

In this post we don’t consider detailly the contraindications, intolerance, serious adverse events, or drug-drug interactions for given agents.

XOI with either allopurinol or febuxostat is the first-line pharmacologic ULT approach. The initial allopurinol dosage should be no greater than 100 mg/day. This should be followed by gradual increase of the maintenance dose, which can safely exceed 300 mg even in patients with CKD.

Also to avoid allopurinol toxicity, the guidelines recommend considering HLA-B*5801 prescreening of patients at particularly high risk for severe adverse reaction to allopurinol (eg, Koreans with stage 3 or worse kidney disease and all patients of Han Chinese and Thai descent).

For all 9 cohorts when the serum urate target has not been met and/or with continuing disease activity, ACR recommended upward dose titration of the XOI to the respective maximum appropriate dose for the individual patient. If upward titration of the initial XOI agent was not tolerated or did not achieve the serum urate target, substitution of another XOI was an appropriate first-line option. However, if XOIs were contraindicated or not tolerated, consider uricosuric medications as alternative. Note that the unachieved target and/or continuing disease activity is with the presupposition that [1] nonpharmacologic ULT have been applied; [2] appropriate treatment and antiinflammatory prophylaxis are employed for attacks of acute gouty arthritis.

The TFP recommends single XOI therapy with either allopurinol or febuxostat as the first-line pharmacologic approach (evidence A). If XOI is contraindicated or not tolerated, probenecid is recommended as an alternative first-line pharmacologic ULT option. But FTP did not recommend probenecid as a first-line ULT monotherapy in those with a creatinine clearance below 50 ml/minute.

Pharmacologic ULT could be started during an acute gout attack, provided that effective antiinflammatory management has been instituted. Regular monitoring of serum urate (every 2-5 weeks) during ULT titration is recommended. Once the serum urate target is achieved and maintained the frequency of monitor could be prolonged to every 6 months.

If with the approach above, the serum urate target remained unachieved or continuing disease activity remained, we should titrate the dosage of the first-line single drug to the maximum tolerable dose. If issue remains despite maximum or maximum dosage is not tolerated, approach two is to add uricosuric agent to XOI. Note that the unachieved target and/or continuing disease activity is with the presupposition that [1] nonpharmacologic ULT have been applied; [2] appropriate treatment and antiinflammatory prophylaxis are employed for attacks of acute gouty arthritis.

If with approach two, the serum urate target remained unachieved or continuing disease activity remained, pegloticase might be considered as the last approach. However, pegloticase treatment shoud be limited to gout patients with severe gout disease burden and refractoriness to, or intolerance of, appropriately dosed oral ULT options.

After palpable tophi and all acute and chronic gouty arthritis gout symptoms have resolved, ULT should be continued in order to maintain serum urate <6mg/dL indefinitely.