Gout Management

Posted on Apr 6, 2010 in Expired CME | 0 comments

Front-line Issues in the Management of Gout

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Learning Objectives

As a result of this activity, the learner will be able to

1. Identify that the long-term goal of gout treatment is to reduce serum urate to less than 6.0 mg/dL and the importance of monitoring serum urate levels
2. Provide patient education regarding long-term commitment to treatment adherence, including lifestyle and pharmacologic interventions

Information

Gout is a form of inflammatory arthritis, with metabolic sequelae, triggered by the deposition of monosodium urate (MSU) crystals within the joints and tissues. This can lead to tophus formation in and around the joints and uric acid urolithiasis, and is associated with hyperuricemia. The deposition of the MSU crystals acts as a catalyst for the inflammatory reaction that is recognized as acute gout.

Pathophysiology

Hyperuricemia, defined as serum urate more than 6.8 mg/dL, is a common biologic phenomenon and is the most important risk factor in the development of gout. Serum urate levels are generally higher in men, and data from Taiwan has shown that approximately 28% of males are hyperuricemic compared with 11% of females (Figure 1).[1] A similar distribution is seen in the United States. Serum urate levels tend to be lower in perimenopausal women, due to elevated levels of circulating estrogen. An increase in serum urate may be observed in postmenopausal women, when estrogen levels decrease.

Figure 1. Distribution of Serum Urate Values and Definition of Hyperuricemia[1]

Serum urate concentration of 6.8 mg/dL or more promotes the formation of MSU crystals as the concentration of serum urate increases above the physiologic solubility threshold. Uric acid is the end product of purine degradation in humans. As humans lack the enzyme uricase, which transforms uric acid to the water soluble product allantoin, this results in an accumulation of uric acid in the serum, which is either excreted through the digestive tract or the kidneys.[2]

The Normative Aging Study, which measured the annual incidence of developing gout over 15 years, demonstrated dependence on serum urate levels.[3]Twenty-two percent of men with serum urate levels more than 9.0 mg/dL developed gout within 5 years compared to only 3% of men with serum urate levels between 7.0 and 9.0 mg/dL. Applying these figures to the 2005 population, it suggested that 3 million US adults over 18 years of age are affected by gout annually.

Risk Factors and Comorbidities Associated With Gout

The prevalence of gout is rising; in the past 20 years gout prevalence has more than doubled in the United States alone and is continuing to rise. This rise is being driven by a number of factors, including increased longevity, increased incidence of hypertension, obesity, coronary heart disease, congestive heart failure, chronic kidney failure, all components of metabolic syndrome (coupled with changes in diet), alcohol consumption, high-fructose corn syrup consumption, and the use of concomitant medications such as diuretics, low-dose aspirin, and niacin.[4-6]

The association between gout, hyperuricemia, and hypertension has long been recognized; 20% to 40% of hypertensive patients have gout and, similarly, approximately half of patients with gout are hypertensive.[7] Several studies have shown that hyperuricemia is independently associated with hypertension: 1 study showed that the risk of developing hypertension was increased by 80% in patients with hyperuricemia.[8] First-line therapy for hypertension includes loop and thiazide diuretics, both of which are associated with hyperuricemia and thus gout.[9]

Gout is associated with an increased risk of cardiovascular disease (CVD). MRFIT (the Multiple Risk Factor Intervention Trial) studied more than 9000 males for 17 years and found that gout accompanied by an elevated serum urate level imparted a significant independent CVD mortality risk.[10]

Obesity is another important risk factor for gout. Elevated body mass index (BMI) and insulin resistance are associated with hyperuricemia and gout. As approximately 60% of Americans are defined by BMI as overweight, and one-third as obese, it is important to understand this association.[11]

Impaired renal function and kidney disease can result in reduced excretion of urate and subsequent hyperuricemia and gout. This relationship is complex, as impaired renal function can also be secondary to gout due to the deposits of MSU crystals in the kidneys causing kidney damage.[12]

Metabolic syndrome is a group of interrelated conditions (including obesity, hypertension, hyperlipidemia, and insulin resistance) that affects more than 50 million US adults.[13] There is a close association between the presence of metabolic syndrome and gout, with 70% of gout patients having metabolic syndrome.[4,6]

Clinical Stages of Gout

When serum urate levels exceed 6.8 mg/dL, MSU crystals may be deposited in the joints. Local trauma, or a drop in temperature, may then initiate the release of cytokines, causing inflammation.[14] Not all patients with elevated serum urate will experience a gout attack, a condition known as asymptomatic hyperuricemia. The first attack of gout is typically monoarticular and affects the lower extremities, in particular the first metatarsophalangeal (MTP) joint of the foot. In the elderly (especially in postmenopausal women), gout may present as polyarticular disease affecting small joints and fingers, bursae, or tendons.[14]

Although a gout attack is self-limiting (7-10 days), the crystals remain in the joints, causing low-grade inflammation and ongoing tissue damage.[15,16] (This is known as the intercritical period.) If gout is allowed to progress, advanced gout will develop, leading to tophaceous deposits, cartilage loss, and bone erosions.[2]

Case Study

Mr. W, a 52-year-old accountant, has a follow-up visit with his primary care clinician (PCC) following a change in his medication for hypertension. He has previously been advised to lose weight, and although he was initially successful, reducing his BMI from 32 to 30, his weight has remained static for the last 6 months.

During his visit Mr. W complains of intense pain in his right big toe, which is red and swollen. The pain began 2 nights ago and has not subsided with the use of over-the-counter anti-inflammatories. This is the first time he has experienced this type of pain and has no recollection of any trauma. He also has a low-grade fever, but otherwise feels well.

The following discussion highlights additional information from Mr. W that would help in diagnosing this new complaint, accompanied by appropriate tests that could be carried out, and advice on how best to manage Mr. W’s symptoms.

Diagnosing Gout

In a patient presenting with symptoms such as these, gout should be suspected. To make a presumptive diagnosis of gout, the patient’s history is very important. Questions to ask include–

• How long has the patient had the symptoms?
• How rapidly did it progress?
• How painful is the attack, on a scale of 1 to 10?
• Which joint is affected?
• Is there redness/swelling of the joint?
• Has the patient ever experienced anything like this before?
• Has the patient’s medication changed recently? (a particularly important question in this case)
• What is the patient’s lifestyle like? (diet, exercise, alcohol consumption, smoking)
• Have any relatives suffered a similar complaint?

Physical examination of the patient is also very important.[17] The American College of Rheumatology (ACR) has established preliminary criteria for the classification of acute gout (Box 1). If the patient fulfills 6 or more of the ACR criteria, gout should be suspected.

Box 1. Criteria for the Classification of Acute Arthritis of Primary Gout[18]

Laboratory and nonlaboratory investigations can be helpful in confirming the diagnosis of gout and should include serum urate levels, although up to 50% of patients will have a normal serum urate level during an attack. A complete blood count may suggest myeloproliferative disorders or septic arthritis. Fasting lipid and glucose levels, and serum creatinine values, are helpful when evaluating patients for the presence of comorbidities associated with gout, while radiographic or ultrasound imaging can detect the presence of tophi.[19,20]

Differential Diagnosis

There are a number of differential diagnoses that are important to consider when examining the patient with presumed gout. The most important is septic arthritis, an infection of the joint that must be treated within 24 to 48 hours, as it could result in permanent joint damage. If septic arthritis is suspected, an immediate rheumatology or orthopedic consultation is required.

Patients with pseudogout may present with symptoms that mimic gout. It can be distinguished from gout by differences in the crystals identified in joint fluid (calcium pyrophosphate dehydrate [CPPD] crystals rather than MSU) and the appearance of chondrocalcinosis on X‑rays. CPPD crystals are weakly birefringent rhomboids, rods or squares, while MSU crystals are negative, strongly birefringent, and needleshaped.[17]

Other conditions to consider are osteoarthritis of the first MTP joint, psoriatic or reactive arthritis, or monoarticular rheumatoid arthritis. Cellulitis can affect the skin over joints that are typically affected by gout.

Identifying MSU crystals in aspirated synovial fluid will definitively diagnose gout; however, in primary care less than 10% of gout cases are diagnosed by this method.[21,22] Likely reasons for this are patient reluctance to have a needle inserted into an intensely painful joint, inexperience of the PCC in performing a joint aspiration, limited access to a polarizing light microscope, and time pressures.[23] For a PCC, a more practical approach is to adhere to the ACR guidelines to diagnose gout using clinical, laboratory, and radiological findings, only referring the patient for joint aspiration if septic arthritis is a consideration.

Managing a Gouty Attack

Once it has been established that the patient is suffering an acute gout attack, the main objective is to treat the pain and inflammation. Important aspects to consider in an acute attack are early treatment, and the dose and duration of an appropriate medication based on the patient’s comorbidities. Available options include–

• Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs are the first-line therapy, particularly in the United States. The US Food and Drug Administration (FDA) has only approved indomethacin, naproxen, and sulindac for acute gout, but any NSAID can be used. NSAIDs should be prescribed immediately after the onset of symptoms at a maximum dose for 2 to 3 days, and then the dose tapered over 7 to 10 days. Treatment should continue for a few days after the attack has resolved.[24] The use of NSAIDs needs to be carefully monitored, especially in patients at increased risk of side effects associated with NSAIDs, such as the elderly and those with a history of peptic ulcer disease, chronic kidney disease (CKD), or CVD.

• Colchicine: Generic colchicine has been available for decades for the treatment of acute gouty attacks. Traditionally it was administered as 0.6 mg every hour until the gout attack resolved or the total dose had reached 8 to 9 pills. Branded colchicine was approved by the FDA for the treatment of acute gout in August 2009 at a dosage of 1.2 mg. It is a useful option in patients unable to take NSAIDs. Standard treatment is to initiate prophylactic treatment with 2 doses of 0.6 mg and then 1 hour later a dose of 0.6 mg. This has been shown to be as effective as prolonged courses of generic colchicines, which has severe gastrointestinal side effects such as diarrhea.[25,26] There is no longer a role for IV colchicine.

• Corticosteroids: Oral corticosteroids are a good alternative when NSAIDs and colchicine are contraindicated, such as in CKD. Oral prednisone can be given at doses of 30 to 40 mg per day for 5 to 10 days. Corticosteroids are highly effective and are usually well tolerated. Intra-articular corticosteroid injections are a useful option in patients with only 1 or 2 joints affected[23]; they provide rapid relief but should not be used in patients where there is suspicion of a septic joint.

Sixty percent of gout patients will experience a second or third gout attack within 1 year of their first attack, and patients should be advised to start taking prophylactic NSAIDs or corticosteroids as soon as they perceive an attack to be occurring.

Once the acute attack has resolved, it is important to reduce uric acid levels to prevent deposition of MSU crystals that can result in chronic tissue damage (but not during the attack). [27]

Box 2. Acute Gouty Arthritis: Diagnosis

Lowering Serum Urate – Nonpharmacological Approaches

Nonpharmacological treatment is the first approach to lowering serum urate and should begin with patient education and lifestyle changes. The patient should be counseled to reduce his weight through a calorie-restricted diet and to reduce consumption of red meat, shellfish, and food and drink containing high-fructose corn syrup. These dietary changes can reduce serum urate by 1.0 to 2.0 mg/dL.

Many patients do not adhere to these low-purine diets, finding them unpalatable.[28,29] Instead, it may be more successful to counsel the patient to moderate foods that are known to aggravate gout, such as organ meats, and to limit alcohol consumption. Beer has a high content of the purine guanocine, which increases uric acid production, and therefore beer intake should be limited; spirits and wine have less of an effect.[30,31] Patients should also increase their intake of vitamin C and low-fat dairy products, as both have been shown to be uricosuric, and there is some evidence that coffee may have a beneficial effect.[28,32-34]

Case Study

(continued)
Mr. W returns to his PCC 3 weeks later for a follow-up appointment. The pain and swelling decreased within 5 days with the use of NSAIDs. Laboratory test results showed an elevated serum urate of 7.9 mg/dL, high CRP levels, and a creatinine clearance (CrCl) of 55 mL/min. Soft tissue swelling was seen on plain X‑ray.

How should Mr. W be managed in light of his increased risk of further attacks of gout? Would it be appropriate to initiate urate-lowering therapy (ULT) at this stage?

A review of the patient’s medication prescribed for comorbid conditions should be undertaken, and changes should be made where appropriate. For example, diuretics prescribed for hypertension act by increasing reabsorption of urate anions in the kidney, which promotes hyperuricemia and increases serum urate levels.[35] Consideration should be given to prescribing an alternative such as losartan, which is known to have a uricosuric effect.

Indications for Urate-Lowering Therapy (ULT)

ULT is recommended for patients who have multiple (2 or more) attacks of gout per year, evidence of advanced disease as seen with imaging techniques or by the presence of tophi, joint damage, persistent synovitis, recurrent urolithiasis, or defined uric acid overproduction (which, although rarely seen, needs to be treated as early as possible).[27,30] There is currently lack of agreement over these recommendations, with some believing ULT should be initiated after the first attack of gout, based on evidence that around 60% of patients will experience a second attack within 1 year,[17] as opposed to the other school of thought which argues that patients may not experience another attack of gout for years, and the patient may be unwilling to take, or comply with, life-long therapy.[23]

Thus, the decision to initiate ULT varies with each individual patient, depending on the severity of the acute attack, the presence of comorbid conditions, and the patient’s risk of future attacks.

The overall clinical goal of ULT is to reduce the serum urate to less than 6.0 mg/dL in order to eliminate acute attacks and flares, resolve tophi, and reduce chronic gouty arthropathy. Patient-centered goals are very important – to reduce their pain, reduce their disability, and improve their quality of life.[36]

When Should ULT Be Initiated?

Whether initiated after the first or second gout attack, ULT should not be commenced during an acute attack, as lowering serum urate can further increase the risk of a painful flare[37]; rather, ULT should be initiated 1 to 2 weeks following the acute attack. Once ULT has been initiated, it is important that anti-inflammatory prophylaxis is prescribed, such as NSAIDs or colchicine, to reduce this risk of increased gout attacks. Prophylaxis should be continued for at least 6 to 12 months, as it can take several months for the body urate pool to return to normal and all the MSU crystals to be mobilized.[38]

Once ULT has been initiated, it is important to regularly monitor serum urate levels to ensure that the target of 6.0 mg/dL is reached and maintained, with dose adjustment as necessary. Improved outcomes have been seen in patients who achieve serum urate reduction to the target level of lower than 6.0 mg/dL, with reduced frequency of gout attacks, reduced tophus size or tophus resolution, depletion of uric acid stores and crystals in the synovial fluid, and improved renal function.[39-41]

In addition, the patient will need to be counseled that ULT may initially be associated with an increase in gout attacks; however, these will decrease with continued use of ULT, and as a result of the use of prophylactic NSAIDs or colchicine during the first 6 to 12 months of ULT (Box 3).[38] It is essential that the patient understands that ULT is a lifelong commitment and should not be stopped, even once the gout flares have ceased to occur.[39-41]

Box 3. Managing Patient Expectations With ULT Improves Adherence and Outcomes[38]

ULT

There are 3 types of therapies available for treating gout; these include uricostatic drugs (xanthine oxidase inhibitors), uricosuric drugs, and uricolytic drugs. Whatever the choice of ULT, it needs to be tailored to the individual patient depending on that person’s comorbidities and concomitant medications.

• Uricostatic agents: The most commonly used urate-lowering agents are uricostatic drugs, which act as inhibitors to xanthine oxidase, ultimately blocking the conversion of hypoxanthine and xanthine to insoluble uric acid and thus preventing the basis of the problem encountered in gout. Xanthine oxidase inhibitors are effective agents both in overproducers and underexcretors of uric acid.[26]

Allopurinol has been the first choice of ULT since the 1960s. Recently a new xanthine oxidase inhibitor, febuxostat, was introduced, which, unlike allopurinol, is a nonpurine analogue.

Allopurinol is a structural analogue of hypoxanthine that competitively inhibits xanthine oxidase. It should be administered at a starting dose of 100 mg/day and the dose increased by 100 mg daily every 1 to 4 weeks until the target serum urate level of lower than 6.0 mg/dL is reached. Despite the FDA approving allopurinol up to a maximum dose of 800 mg/day, the most commonly prescribed dose is 300 mg (95% of prescriptions are written for 300 mg/day or less).[42] At 300 mg/day, numerous studies have shown that only 21% to 55% of gout patients achieve the target serum urate level.[43] Reasons given for allopurinol dosing not exceeding 300 mg/day include the safety of allopurinol not being well-defined, especially in patients with CKD, lack of familiarity of PCCs with doses exceeding 300 mg/day, and unwanted side effects such as skin rash (10% of patients), gastrointestinal problems, and hepatotoxicity in approximately 5% to 10% of patients. In rare cases, allopurinol can trigger major cutaneous reactions, such as Stevens–Johnson syndrome and hypersensitivity syndrome, a potentially life-threatening condition usually occurring within 3 to 4 weeks of starting the drug.[44,45] Risk factors for allopurinol hypersensitivity include renal dysfunction, hepatic disease, and thiazide diuretic use.[46]

Febuxostat is an orally administered, selective xanthine oxidase inhibitor recently approved by the FDA at doses of 40 and 80 mg once daily. The structure of febuxostat differs from allopurinol as it is a nonpurine analogue, lacking the purine-like backbone seen in allopurinol. Febuxostat is mainly metabolized by the liver, requiring minimal renal clearance, and therefore requires no dose adjustment in patients with mild-to-moderate renal or hepatic dysfunction.[47,48]

The most robust data for the efficacy and safety of febuxostat comes from a large pivotal 6‑month, randomized, double-blind Phase III clinical trial, CONFIRMS (Confirmation of Febuxostat in Reducing and Maintaining Serum Urate), which compared the efficacy of febuxostat and allopurinol in reducing serum urate to lower than 6.0 mg/dL. The study randomized 2269 patients to febuxostat 40 mg or 80 mg/day, or allopurinol 300 mg/day. Of these patients, 1483 had mild-to-moderate renal impairment, and those in the allopurinol treatment arm were dosed according to renal function at 200 mg/day. Efficacy of febuxostat 40 mg/day was comparable to that of allopurinol, while a significantly greater efficacy was observed in the 80 mg/day febuxostat group (P<.0001). In patients with mild-to-moderate renal impairment, febuxostat at either dose demonstrated significantly greater efficacy than allopurinol. A limitation of the allopurinol efficacy was possibly due to high mean baseline serum urate levels and the fixed rather than titrated doses of allopurinol (Table 1).[49-52]

Table 1. Comparative Trials of Febuxostat and Allopurinol

• Uricosuric agents: Probenecid is the only uricosuric drug approved in the United States and it has long been established to be effective for reducing serum urate in patients without renal impairment.[26,53] Uricosuric drugs act by inhibiting postsecretory serum urate reabsorption, and thereby correcting renal urate underexcretion.[26] Probenecid is excreted renally, so is not suitable for patients with kidney disease. It is rapidly excreted, so is more effective in 3 daily doses, but it is most commonly prescribed twice daily, as multiple dosing can lead to poor patient compliance. Probenecid can trigger urolithiasis, and patients taking it need to increase their water intake to alkalinize their urine. Probenecid is ineffective with a CrCl less than 50 to 60 mL/min, and the large number of drug-drug interactions probenecid displays warrant caution.[5,54]

Other uricosuric agents include losartan, which has been shown to reduce serum urate by 20% to 25% in healthy volunteers, hypertensive patients, and cardiovascular transplant patients[55]; fenofibrate, which has been shown to decrease serum urate in patients with chronic tophaceous or recurrent gout when used in combination with other urate-lowering agents[56]; and atorvastatin, which in a randomized trial was shown to significantly reduce serum urate levels.[57] It should be noted, however, that losartan, fenofibrate, and atorvastatin are not FDA approved for the treatment of gout and hyperuricemia.

• Uricolytic agents – emerging and investigational therapies for gout: The enzyme uricase, which catalyses the conversion of uric acid to allotonin, is another therapeutic target as a potential therapy for gout. Pegloticase is pegylated, recombinant mammalian urate oxidase. It is currently in late-phase development to lower serum urate levels and promote accelerated tophus dissolution.[45,58,59] In early trials, pegloticase has demonstrated an ability to lower serum urate levels and debulk tophi; it is given intravenously, and infusion reactions have been reported. The drug is immunogenic, and loss of efficacy has been reported after several months of treatment.[58-60]

Tophus size reduction with pegloticase was investigated in 2 Phase II randomized, double-blind clinical trials for treatment-failure gout, the GOUT 1 and GOUT 2 trials.[61] Patients received pegloticase 8 mg every 2 or 4 weeks. Patients receiving 8 mg every 2 weeks showed a 40% reduction in tophus size, with 20% of patients showing complete resolution by week 13. A complete response was defined as complete resolution of 1 or more tophus without an increase in size of other tophus or development of new tophi. In GOUT 1, serum urate less than 6.0 mg/dL was achieved by 47% of patients receiving pegloticase every 2 weeks compared to 20% of those on 8 mg every 4 weeks. In the GOUT 2 trial, the target SU level of 6.0 mg/dL was achieved by 38% of patients taking pegloticase 8 mg every 2 weeks and 40% of those taking 8 mg every 4 weeks.

The development of antipegloticase antibodies, the cost, inconvenience of intravenous administration, and infusion reactions remain problematic, so the use of pegloticase may need to be restricted to a subset of treatment-failure gout patients for short-term use to debulk tophi.

The role of interleukin-1 (IL‑1) inhibition in gout is also being investigated with rilonacept, which has been shown to reduce pain and inflammation in patients with gout.[62] Anakinra, another IL‑1 inhibitor, is also undergoing clinical trials in gout patients.[63] Both have demonstrated positive results in early clinical trials.

Case Study

(continued)

Following a treatment regime with allopurinol at a starting dose of 100 mg and increased every 3 to 4 weeks to 300 mg, a change of hypertensive medication, and advice on weight reduction, lifestyle changes, and the importance of adherence to the ULT even though flares will be experienced, Mr. W is seen for a 6‑month follow‑up visit. Serum urate monitoring showed a steady decrease in urate levels from 7.9 mg/dL to 7.0 mg/dL, his hypertension is being well controlled with the new medication, and his CrCl remains low at 58 mL/min. He admits he has found the flares hard to cope with despite taking prophylactic NSAIDs, and adherence has not been easy. He understands the importance of following the doctor’s advice, but he feels disillusioned about the treatment.

Although Mr. W has shown a decrease in his serum urate levels to 7.0 mg/dL, he still needs to reach the therapeutic target of 6.0 mg/dL. In light of Mr. W’s low CrCl, would it be appropriate to increase the dose of allopurinol above 300 mg? If not, what would be an alternative agent?

The safety of allopurinol above 300 mg/day is not well studied in patients with renal impairment or hepatobiliary disease, or those taking certain concomitant medications, and it is normal for dose adjustments to be made to the allopurinol dosing in patients with reduced CrCl.[26,64,65] Allopurinol also has known drug-drug interactions with antibiotics, antiarthritics, blood-thinning agents, and thiazide diuretics.

Thus, high allopurinol doses may be inappropriate for Mr. W. He should be advised that, with careful and regular monitoring, it may be possible to slowly increase the allopurinol dose in order to achieve the target serum urate value. Mr. W is unsure he wants to take this route, as he has been researching his condition and medication on the internet and is aware that there is little evidence presently available to support taking a higher dose of allopurinol with reduced kidney function. Feeling that he will not adhere to a higher dose of allopurinol because of fear of an adverse reaction, he requests an alternative medication.

At this stage it would be appropriate to change his urate-lowering medication to the nonpurine, selective xanthine oxidase inhibitor febuxostat, initially at a dose of 40 mg once daily, in an attempt to further lower his serum urate level. Concurrent use of NSAIDs with close monitoring of renal function should also be continued, as flares are still likely to occur as the remaining uric acid is mobilized.

After 6 weeks Mr. W’s serum urate has continued to decrease to 6.4 mg/dL, he has experienced 1 flare that was successfully controlled with NSAIDs, and treatment was not interrupted.

Long-term Advice to the Patient

Since the serum urate level is still not below 6.0 mg/dL, increasing the dose of febuxostat to 80 mg/day should be considered, with continued monitoring of serum urate levels.

Re-emphasize to the patient that flares are likely to continue until the serum urate has decreased to the target level and stabilized, and therefore continued prophylactic NSAIDs are important. The patient needs to understand that this is a lifelong treatment and that once the flares are reduced and the prophylactic treatment is stopped, it is vital that the ULT is continued. Explain to the patient that if the ULT is stopped, the MSU crystals will start to build up again and be deposited around the joints, and his gout attacks will reoccur. In order to avoid this, treatment must be taken life-long.

Conclusion

The prevalence of gout is increasing, in line with increasing comorbidities and the aging population, making the disease more difficult to treat. Hyperuricemia leads to the formation of MSU crystals and ultimately gout, which if left untreated can cause joint damage. Long-term intervention with urate-lowering drugs is needed to reduce the serum urate level and control the disease. Lifestyle changes alone rarely reduce the serum urate level to less than 6.0 mg/dL for prolonged periods of time.

Allopurinol has traditionally been the first-line treatment for gout, but there are several limitations, especially in patients with renal impairment, where the dose needs to be adjusted according to renal function.

Febuxostat is a newly approved drug for gout and a useful first-line alternative to allopurinol. Moreover, it can be used in patients with mild-to-moderate renal impairment. Several other therapies are currently undergoing testing in clinical trials. The recent introduction of new therapies for gout aims to clinically improve the modern-day management of this disease.

Robin Dore, MD
Published on April 13, 2010

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