Comprehensive Disease-Management Plan

Introduction

The long-term goals of comprehensive gout management are closely linked, with each step promoting the effectiveness of the other steps in the therapeutic chain (Figure 11-1). Achieving patient adherence and “buy in” to the treatment program is critical. Patient education via effective communication, should start early in therapy and clearly convey that gout is a disorder of excess body stores of uric acid and that urate-lowering therapy (ULT) is the only “curative” measure for gout management (see Patient Education in Gout) (Figure 11-1). Effective gout therapy begins with the assurance for the diagnosis, followed by aggressive and prompt management of acute flares, anti-inflammatory prophylaxis against flares during the early phases of ULT, and, most importantly, the life-long use of adequate doses of ULT (Figure 11-2). Comprehensive management also includes long-term monitoring of outcomes such as serum urate levels and patient functionality and participation in life enhancing activities. The steps needed to confirm the diagnosis of gout are outlined in Diagnosis of Gout and Synopsis and Assessment of the 2015 Gout Classification Criteria. The details of pharmacologic and nonpharmacologic approaches to managing the acute and chronic stages of gout are found elsewhere in this book.

How and when these treatment schemes should be applied in a patient with gout is the subject of this section. The approach to individual subjects will vary depending on severity and chronicity of symptoms, degree and cause of hyperuricemia, tolerance to anti-inflammatory and urate-lowering drugs, and the type and number of comorbid medical conditions. A very generalized algorithm is presented in Table 11-1.

Patient education has been shown to be the most important predictor of successful comprehensive gout management.^1,2 This education should begin at the time of the very first flare and should emphasize that gout is a progressive metabolic disease that can ultimately lead to disability and joint destruction. The health care provider should discuss how diet and lifestyle modifications can help overall health and lessen the frequency and severity of gouty flares but should also make it very clear to the patient that without compliance to the prescribed ULT, the accumulation of urate in the body will continue and the disease will progress (Patient Education in Gout) (Table 11-2). While the discussion about diet and attention to weight loss in patients who have overweight and obesity is very important, the physician should not imply that gout can be managed by diet alone. Many restrictive and unpalatable diets have been touted for gout but have only had the effect of turning the patient away from medical care. The essence of what most gout patients need is a sensible, calorie-restrained or calorie-restricted diet that minimizes red meat, shellfish, starches and alcohol. The diet should emphasize fish, poultry, vegetables, nuts, legumes and nonfat dairy products (Approach to Diet, Alcohol and Other Lifestyle Factors).

Physical exercise is also important and hydration must be maintained to prevent a decrease in glomerular filtration rate (GFR) and optimize renal urate anion handling. Weight loss (when appropriate) and improved control of hypertension, diabetes mellitus and dyslipidemia have all been shown to have a positive effect on overall health and are associated with lowering uric acid and improving the course of gout.

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Acute Gout Management

A patient presenting with an acute gout flare is typically in great pain. At this stage, the physician should be primarily focused on alleviating the pain as soon as possible. A good history may identify any “triggers” for the flare and this may help minimize the frequency of future flares. At this stage, new or intensified attempts to lower the uric acid level will likely only worsen or prolong the flare. Established urate-lowering drugs should not be stopped or changed in dose during acute gout since this can trigger a worsening or prolongation of the flare.

The pain of gout is caused by a cascade of events in the joint involving crystals interacting with cells, cytokine release and intense phagocyte infiltration (Disease Definition). All of these events are well under way in the first 8 to 12 hours of gout symptoms. For this reason, the sooner anti-inflammatory therapy is started in a gout attack, the more likely it will be of some benefit. Therapies started after 72 hours of symptoms generally result in little improvement. The choices of therapies listed in Table 11-3 are all effective if initiated early enough. Each has its own particular side effect profile and needs to be used with caution in various disease states. Whichever medication is chosen, it is important to remember that the usual duration of gouty flares in the first years of disease is usually 5 to 10 days if untreated. It is important that the anti-inflammatory schedule cover that duration at a minimum. In later stages of gout, flares can last 10 to 20 days and coverage should be expanded in those situations. Refer to Figure 6-2 in Management of Acute Gouty Arthritis for a gout flare management algorithm from the 2016 European League Against Rheumatism (EULAR) guidelines.

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Initiating ULT and Use of Gout-Flare Prophylaxis

Recommendations as to when to initiate ULT have changed over the past few decades, with the general tendency to treat patients earlier. Most international guidelines agree that when a patient experiences two or more attacks of gout per year, ULT should be started. There is little evidence-based support for this recommendation. If we consider gout a disease of gradually accumulating urate burden that will not stop or recede until serum urate levels are reduced below target values, one could certainly make an argument for beginning ULT after the initial flare. A discussion about the eventual need for ULT should certainly begin at that time. In more advanced stages of gout where tophi are present, gouty erosions are present on radiographs, or if the patient has had an episode of nephrolithiasis in addition to his or her gout, ULT is necessary. There is no consensus yet on when to use advanced imaging (Diagnosis of Gout and Use of Laboratory and Imaging) to help with therapeutic decision-making in in gout. The various drugs used for ULT and their toxicities are outlined in Pharmacologic Urate-Lowering Therapy.

When starting ULT (Table 11-4), anti-inflammatory prophylaxis is indicated for the first 3-6 months; although it was previously thought optimal to withhold ULT until 1 to 2 weeks of prophylactic therapy had been given, current consensus based on available data favors not delaying ULT initiation. In general, ULT is continued lifelong unless the secondary causes of the patient’s hyperuricemia have been eliminated and a serum urate <6.0 mg/dL can be maintained without urate-lowering drugs. The gout-flare prophylaxis (e.g., low-dose colchicine) should be continued for at least the first 3-6 months of ULT and thereafter continued, if necessary, for at least 3 months after the target serum urate level of <6.0 mg/dL has been reached or the patient has had no further gout attacks. In those with visible tophi, gout-flare prophylaxis often has to be continued until these tophi resolve.

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Reaching the Target Serum Urate Level

While reducing the serum urate level to <6.0 mg/dL is a widely accepted target, there is evidence in patients with chronic gout and tophi that a lower serum urate target value of 4.0 mg/dL or less would result in a better outcome, due to accelerated “debulking” of tophi. That level of urate reduction is difficult to achieve with oral uricosurics or xanthine oxidase inhibitors alone; such reduction in urate burden can be obtained in patients taking either allopurinol or febuxostat in combination with a potent uricosuric such as probenecid or with pegloticase by itself.

It should be noted that the uricosuric mechanism of action differs from that of both allopurinol and febuxostat. The authors, in their clinical practices, commonly add a uricosuric to allopurinol or febuxostat, to reach a lower serum urate target. One caveat is that probenecid has the potential for multiple drug interactions; a substantial consideration since polypharmacy is common in gout patients. Table 11-5 lists a number of commonly used medications and dietary components (or supplements such as ascorbate)nthat have some urate-lowering properties. Occasionally, these agents can be used to treat comorbid conditions and, at the same time, have a beneficial effect on achieving the desired degree of uric acid lowering, including in refractory hyperuricemia (see Difficult Gout and Hyperuricemia).

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Take-Away Messages

• Treat acute gout flares early with lower doses of colchicine or with an NSAID (or a coxib) or robust doses of corticosteroids.
• Identify and treat comorbidities and consider cause of hyperuricemia.
• Initiate ULT (once the flare has passed) in those with:
  • Frequent flares (≥2 per year)
  • Tophi
  • Uric acid overproduction
  • CKD
• History of urolithiasis
  • Difficult-to-treat gout (due to comorbidities or severe flares such as polyarticular gout)
• Initiate gout-flare prophylaxis (adjust colchicine dose for renal function).
• Treat to serum urate target of <6.0 mg/dL at a minimum. With one or more tophi detected on physical exam, a lower serum urate target of <5.0 mg/dL is appropriate, and an even lower serum urate target (<4.0 mg/dL) is appropriate in patients with very advanced gout.
• Monitor serum urate levels every 1 to 2 months when starting treatment, then at least 1 to 2 times per year.
• Educate patients about the role of diet, alcohol, and dehydration in gout and hyperuricemia; the possibility of flares upon initiation of ULT; that gout is a disorder of excess body stores of uric acid and therefore that ULT is the only “curative” measure in gout; and the importance of adherence to treatment.
• Do not stop and start ULT because of gout flares.
• Poor treatment responders should see a rheumatologist and be considered for combination therapies with a xanthine oxidase inhibitor and a uricosuric, or the use of pegloticase by itself in severe cases of chronic gout.