Key Points
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Comprehensive management of gout involves identifying and addressing comorbid cause(s) of the hyperuricemia, treating and preventing attacks of gouty inflammation, and lowering serum urate to an appropriate target level indefinitely.
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The ideal serum urate target is, at a minimum, less than 6 mg/dL (360 μmol/L). The serum urate target should remain at less than 6 mg/dL indefinitely in all gout patients and should initially be well under that in patients with extensive tophaceous disease until tophi have resolved.
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Patient education and adherence are enormous and often-neglected aspects of the optimal management of gout. Adherence can be monitored in part by continuing, regular assessment of the serum urate level.
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Difficult-to-treat gout often warrants combination drug therapy strategies for both refractory hyperuricemia and chronic tophaceous polyarthritis. Chronic tophaceous gouty arthropathy inadequately responsive to optimized oral antihyperuricemic therapy warrants consideration of the use of pegloticase.
Disclosures: Fredéric Lioté is consultant or has contributed to CME sessions for Novartis France, Novartis global, Mayoly-Spindler, LGV, Ipsen, and Ménarini.
Robert Terkeltaub has recently served as, or is, a consultant for URL, Regeneron, Novartis, ARDEA, BioCryst, Pfizer, Takeda, and Savient.
Dr. Terkeltaub’s research is supported by the VA Research Service.
Introduction
Gout has grown more prevalent (see Chapter 6 ), especially in the United States, and we have accumulated many more cases with difficult management problems. The long-term management goals of gout are closely linked, with each step promoting the effectiveness of the other steps in a “therapeutic wheel” ( Fig. 16-1 ).
Effective Communication to Address the Problem of Poor Patient Adherence in Gout
Achieving patient adherence and “buy in” to the program is critical but is markedly underachieved in gout patients ( Table 16-1 ), especially those who are younger and reported fewer office visits and comorbidities.
| Adherence Rates of ≥80% | |
|---|---|
| Hypertension | 72.3% |
| Hypothyroidism | 68.4% |
| Type 2 diabetes | 65.4% |
| Seizure disorders | 60.8% |
| Hypercholesterolemia | 54.6% |
| Osteoporosis | 51.2% |
| Gout | 36.8% |
Gout requires patient education via effective communication, as discussed in part in Chapter 28. In short, explaining gout and treatment objectives to patients in terms they can readily comprehend (at a basic level of education), and clarifying the important, modifiable comorbidities with which gout and hyperuricemia are associated, must be part of a systematic program approach. This promotes optimum quality of care and outcomes, each aspect of which is covered in chapters elsewhere in this book.
A variety of reliable Internet-based sites exist for practical approaches to physician-patient communication for gout. Handbooks, leaflets, memos, and websites have been implemented in some countries [USA: www.update.com/patient ; http://www.mayoclinic.com/health/gout ; France and French-speaking countries: www.crisedegoutte.fr ) (HON); UK: http://www.ukgoutsociety.org ]. One terse, current monograph for patients available on this subject is cited in Doghramji et al. One approach we have found useful is the analogy of gout being like deposits of matches in and around the joints ( Table 16-2 ).
What to say to the patients with gout in readily comprehensible terms
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Monitoring for Outcome and Quality of Care
The comprehensive gout management plan is consistently monitored for outcome, in part by regular assessment of serum urate level (SUA), and quality of care and quality of life hinge on decreasing acute and chronic arthritis, which should always include appropriate use of antiinflammatory prophylaxis to suppress arthritis attacks in early urate-lowering therapy (ULT).
Unlike most other rheumatic disorders, gout can be quite readily placed into permanent remission and, in some cases, truly cured. Despite that consideration, gout is often mismanaged, with adequately effective ULT either not achieved or not sustained indefinitely as the typical, appropriate measure. With the development of new drug options and treatment guidelines, a better outcome for gout patients is expected. Indeed in 2005, the European League Against Rheumatism (EULAR) reported and then published the first international recommendations for the diagnosis and treatment of gout. The development of EULAR and British Society for Rheumatology (BSR) guidelines, as well as the development of new drugs, stimulated the need for better care and for quality indicators. Deliberation on the American College of Rheumatology guidelines is ongoing at the time this is being written, and will address new epidemiological data and recently approved therapeutics (febuxostat, pegloticase).
Gout Treatment Strategy
Once gout is definitively diagnosed, treatment is dependent on a global strategy that includes five clinical aims, each of which is discussed in detail elsewhere in this book:
- 1.
Evaluation of hyperuricemia and its causes via disorders of renal urate disposition and/or of uric acid production (see Chapter 3 , Chapter 4 )
- 2.
Treatment of acute gout attacks (see Chapter 10 ), as an urgent patient need
- 3.
Gout attack prophylaxis implementation (see Chapter 15 ) followed by ULT (see Chapter 12 , Chapter 13 , Chapter 14 )
- 4.
Identification and management of associated comorbidities, such as the metabolic syndrome, and diet and lifestyle factors (see Chapter 11 , Chapter 19 )
- 5.
Patient (and other health professional) education in order to emphasize adherence to treatment and quality of care and quality of life (see Chapter 17 , Chapter 18 , Chapter 27 )
Evaluation of comorbidities ( Table 16-3 ) and disease severity are parts of any “case-by-case” discussion. These five clinical aims of the strategy have to be systematically considered in every patient presenting with gout, and overall management has to take into account the balance between risks and benefits of drugs at any part of the management. Treatment should be tailored to the individual, but general principles and strategies should be borne in mind.
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Pathophysiology is also a key point to consider when treating gout and guides us in providing key information to the patient. Indeed, gout is a metabolic storage and deposition disease, with gradual accumulation of urate as monosodium urate (MSU) crystals in bone and joints, soft tissues, and sometimes the renal medulla, or precipitation of uric acid uroliths. Urate crystal masses can degrade tissues in bone, joints, bursae, and skin. Reducing body urate burden and MSU crystal mass using efficient ULT can be followed by imaging and clinical means, but relationship to the SUA is very valuable, since the SUA level should be substantially lower than the MSU crystallization threshold (urate solubility limit) of above 6.8 to 7.0 mg/dl for urate in physiologic buffers. This is done by aiming for an SUA target below 6.0 mg/dl, less than 360 μmol/L, in all patients with gout.
Striking differences exist between undertreated and nonadherent gout patients, and “refractory gout,” which is related to patients not able to achieve the target for SUA lowering, and “difficult-to-treat” (DTT) gout, which includes patients with uncontrolled gout attacks. For treatment-refractory disease, DTT patients, or specific settings (e.g., major organ transplantation), referral to a rheumatologist is strongly considered.
This chapter will consider general approaches and drug choices in management and discuss DTT gout with respect to aging, renal dysfunction, patients with uncontrolled recurrent attacks and chronic tophaceous gout arthropathy, and gout in major organ transplant recipients. We also cite differences that exist with respect to drug availability in the United States and other countries, to proper label use according to each drug, and to national (BSR) or transnational recommendations (EULAR).
General Therapeutic Strategy
The strategy schematized in Figure 16-1 should be implemented in all patients with gout with or without comorbidities.
Specific Education on Diet and Lifestyle Factors Pertinent to Gout
Immediately after the first gout attack or the firm diagnosis of gout, the patient should be educated about the disease, with respect to precipitating factors for attacks, the destructive potential of excess urate due to tophi, cardiovascular disease risks, and how lifestyle modifications can lessen the risk for recurrent bouts and other medical complications. A discussion with the patient about diet (given in detail in Chapter 11 ) is vital. In brief, many different diets have been advocated to avoid gout; indeed, diet should be thought of as “nutritional behavior”: restriction of calories and animal protein intake (seafood, shellfish, and meat [especially organ meats]) along with the “portion size” of meals in countries such as the United States, alcohol moderation (especially marked limits or abstinence with respect to beer and prohibition of binges of alcohol consumption), and limitation of intake of table sugar and high fructose corn syrup–sweetened beverages and foods (particularly carbonated beverages [“sodas”] and energy drinks). A shift to diet beverages and maintenance of hydration are core aspects of dietary advice. “Heart-healthy” foods in moderation such as seafood, vegetables, nuts, and low-fat dairy products are encouraged. Physical exercise (30-minute walk per day) is also important in order to consume calories and to help achieve ideal body weight. These measures will contribute also to better control of hypertension, the metabolic syndrome, diabetes mellitus, and dyslipidemia. These lifestyle adjustments should be encouraged and monitored regularly by physicians, other health professionals, and key family members. Diet and physical fitness measures, as illustrated in the Multiple Risk Factor Intervention Trial (MRFIT), can drop serum urate by at least 10% to 15%, but most patients with gout do not achieve a serum urate target of through 6 mg/dL by diet and lifestyle measures alone.
Exclusion of Secondary Hyperuricemia and Gout
As discussed extensively in this book, primary hyperuricemia is related to a combination of genetics, including reduced urinary uric acid clearance, and environmental overload of purines and fructose, and overall calories, with obesity and insulin resistance that largely raise serum urate by inhibiting renal uric acid excretion (see Chapter 4 , Chapter 5 , Chapter 12 ). At time of diagnosis, secondary causes of hyperuricemia should also be considered and can be related to various conditions. Chapter 12 reviews the value of 24-hour and spot urine–based methods to screen and assess for uric acid overproduction relative to the more common condition of uric acid underexcretion. A complete hemogram, liver function tests, urinalysis, and chemistry panel are essential baseline studies in all gout patients, and psoriasis should be ruled out. In those with moderate to severely impaired renal function, spot collection becomes a valuable approach. The 24-hour urine uric acid measurement is used as a more definitive analysis, including after screening of spot urine, in those with preserved renal function.
Commonly, in clinical practice, it is not necessary to screen urine for uric acid excretion values, since the cause of the hyperuricemia is evident (e.g., diuretic or cyclosporine use, advanced renal impairment). Furthermore, the urine testing may not need to be done if the most appropriate first-line ULT option is xanthine oxidase inhibition.
Elimination of Nonessential Drugs That Promote Hyperuricemia
Physicians should systematically consider discontinuing nonessential use of drugs that promote hyperuricemia. Thiazide diuretics are commonly used in patients with hypertension, since they positively impact on hypertension outcomes and are inexpensive. However, diuretics can be switched to other antihypertensive drugs, such as losartan (see Chapter 12 ) and amlodipine, which also has been associated with serum urate–lowering effects in some studies. Chronic heart failure and renal insufficiency may require substantial dosages of loop diuretics such as furosemide, but we know this to be a major contributor to hyperuricemia. Nonessential use of niacin should be discontinued. In contrast, low-dose aspirin (acetylsalicylic acid) should not be discontinued in gout patients requiring cardiovascular event prophylaxis.
Therapy Choices in Acute Gout Management
As reviewed in Chapter 10 , a patient presenting with an acute gout attack is typically in excruciating pain. At this stage, the specific treatment goals for acute attacks of gouty arthritis are rapid analgesia and inhibition of inflammation, such that a swift return of pain-free function can be restored for the involved joint(s) in a safe, highly effective, and cost-efficient manner.
The antiinflammatory therapies used to treat acute gout do reduce pain as well as inflammation in this condition, but analgesics (typically opiates and acetaminophen-paracetamol) and local measures (e.g., rest, elevation, upper limb splint, and topical ice packs) can be used as adjunctive therapies. We do not yet know if topical nonsteroidal antiinflammatory drug (NSAID) gels add significantly to the armamentarium in acute gout.
This crucial part of management, at least for the patient, can be addressed with a variety of antiinflammatory medications ( Table 16-4 ). If therapy with any one of these is initiated promptly after the onset of symptoms, much relief should occur quickly, with unbearable pain becoming bearable as the inflammation resolves. In most drug trials for therapy of acute gout, there is an approximately 50% decrease in pain within 2 to 3 days. The earlier acute gout is treated, the better the clinical response, but this is particularly so when using colchicine (which is most effective if started within the first day of the gouty attack). Duration of gout attack treatment should be long enough (7 to 15 days, optimally with treatment stopped 1 to 2 days after complete resolution of symptoms) to avoid early relapse.
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∗ Has been studied in clinical trial setting where subjects also received acetaminophen and, at onset, IM diclofenac 75 mg, before such regimens were started.
It should be recalled that septic arthritis should have been ruled out since fever, acute phase reagents, and leukocytosis can accompany acute attacks; synovial fluid analysis should be done where appropriate, and in particular if one contemplates using systemic or intraarticular steroids.
Choices of treatment for acute gout ( Fig. 16-2 ) are dictated by the patient’s comorbidities rather than by any evidence-based medicine survey. However, recent antiinflammatory agents such as interleukin (IL)-1 inhibitors have been investigated using “state-of-the-art” protocols (canakinumab, rilonacept), as well as classic medications such as colchicine. New, “lower-dose” colchicine regimens have been implemented in the United States and in Europe.
Choices of NSAIDs and Cyclooxygenase (COX)-2 Selective Inhibition as an Alternative Strategy in Gout
Any NSAID can be considered in acute gout, despite the traditional preference for indomethacin, naproxen, or sulindac, each of which is U.S. Food and Drug Administration (FDA) approved for gout in the United States. Alternatives include other short half-life NSAIDs, such as diclofenac. Full doses should be prescribed for the first 2 to 3 days and then tapered off in most cases. NSAIDs with more favorable gastrointestinal side effect profiles than indomethacin, with naproxen being a prime example, should be used more widely, in our opinion. ∗
Use of high doses of aspirin (acetylsalicylic acid) or of nonacetylated salicylates has not been formally evaluated for urate handling could substantially alter serum urate during the acute gout attack and thereby theoretically worsen acute gout. Also an issue is the time needed for acetylsalicylic acid to reach therapeutic serum levels for adequate analgesia to control the severe pain of gout.
Comparisons of NSAIDs and Corticosteroids
Collectively, the choice of NSAIDs can be decided based on availability, past tolerance, age, risk of cardiovascular ∗
∗ Harmful effects of NSAIDs should be recognized. Bavry et al have shown that there is an increased cardiovascular (CV) risk (CV death, nonfatal myocardial infarction [MI], nonfatal stroke) in patients with hypertension and coronary heart disease ; based upon a nationwide cohort of patients over 30 years old with prior MI, even short-term treatment (less than 7 days) eith most NSAIDs, except naproxen, was associated with increased risk of death and recurrent MI in patients with prior MI. As such, alternatives to short- and long- term treatment with NSAIDs should be considered in this strictly limited from a CV safely point of view.
and gastrointestinal adverse events, cost and reimbursement, and personal prescriber choice. Indomethacin has been considered a “gold standard” in the past, but gastrointestinal and central nervous side effects are substantial with this agent, including in aged patients. High-dose prednisone or prednisolone appears at least as effective as indomethacin (or naproxen) and relatively well tolerated, and it is more cost-effective in most patients.Use of COX-2 Selective Inhibition
Some comparative studies have shown comparable effects with selective COX-2 inhibitors (coxibs) to ketoprofen and indomethacin; indeed, there is noninferiority between lumiracoxib and etoricoxib, and naproxen or indomethacin at full dosage. It should be mentioned that etoricoxib at the dosage used in gout trials (120 mg) has not been approved in Europe. Cardiovascular safety of all COX-2 selective agents clearly remains under review. In addition, the European Committee recommended that the existing contraindication on the use of etoricoxib in patients with high blood pressure that is not adequately controlled should be amended to state that patients whose blood pressure is persistently above 140/90 mm Hg and has not been adequately controlled must not take the medicine. Warnings on the risk of heart-related side effects should also be added, stating that (1) high blood pressure should be controlled before treatment is begun and (2) blood pressure should be monitored for 2 weeks after the start of treatment and regularly thereafter. In gout, cardiovascular safety questions still exist regarding the use of coxibs.
Use of celecoxib is not universally accepted for treatment of acute gout. Importantly, it appears that use of celecoxib to treat acute gout requires substantial doses. Schumacher and colleagues have reported preliminary results in which celecoxib to be as effective as indomethacin in acute gout, and better tolerated. However, substantial doses of celecoxib appeared necessary in a randomized, double-blind, double-dummy, active-controlled trial of acute gout, with onset of pain up to 48 hours prior to enrollment. The study was randomized 1:1:1:1 for celecoxib 50 mg twice daily, celecoxib 400 mg followed by 200 mg on day 1 and then 200 mg twice daily for 7 days, celecoxib 800 mg followed by 400 mg on day 1 and then 400 mg twice daily for 7 days, or indomethacin 50 mg three times daily. The high-dose celecoxib (800/400 mg) regimen was associated with greater pain reduction on day 2 compared to low-dose celecoxib (50 mg twice daily; p = .0014), and it also was superior to the middle-dose celecoxib regimen. The high-dose celecoxib 800/400 mg regimen gave results for pain relief from baseline to day 2 comparable to indomethacin 50 mg three times daily but was better tolerated.
Colchicine
The EULAR and BSR recommendations have mainly focused on NSAIDs as a first-line choice for acute gout, since colchicine was not widely used in North European countries. By contrast, in southern European countries such as Spain, Portugal, France, Italy, and even Switzerland, colchicine is long used as a therapeutic but also as a “diagnostic” compound in gout, but that practice is unreliable.
In the United States, a recent randomized, placebo-controlled trial (AGREE) has shown that low-dose oral colchicine 1.8 mg self-administered by the patient over 2 hours, and given within the first 12 hours after acute attack began, was as effective as high-dose 4.8 mg colchicine (given in divided doses over 7 hours) on day 1. With this regimen, 38% of patients are expected to be responders, meaning that additional therapy should be necessary in other patients. EULAR recommendations, based on expert opinions, suggested that a low colchicine dose of up to 1.5 mg (0.5 mg twice daily) daily will be effective in some patients.
Therefore, a low-dose colchicine regimen is now advocated for early gout and is a regimen the patient can quickly self-administer to limit acute gout attacks. Gout patients can also test their sensitivity to such a colchicine regimen at the inception of gout attacks, early in the course of their disease. There is absolutely no evidence basis to support “inundating” the patient with early gout attack with repeated doses of colchicine clustered over several hours. This opinion is buttressed by key pharmacokinetics and side effects results of the AGREE trial ( Figs. 16-3 and 16-4 ). In particular, both low- and high-dose colchicine attained circulating C max of approximately 6 ng/ml in the AGREE trial (see Fig. 16-3 ) under conditions where their efficacy was comparable but total drug exposure was proportional to dose and, under these conditions, toxicity was remarkably high in the high-dose colchicine group, but no significant difference was seen between placebo and low-dose colchicine (see Fig. 16-4 ).
When colchicine is started later than 12 hours after flare onset, 1.5 or 1.8 mg might be inefficient. One option is to increase colchicine dosage up to the maximum daily dose allowed by each current national formulary. In France, the current updated maximal colchicine dosage is 3 mg/day, but, in our opinion, a superior option is to add another therapeutic to the low-dose colchicine, such as an NSAID or corticosteroid, for refractory acute gout.
It is not advised in the U.S. to use extra colchicine for an acute gout attack that occurs despite 1 mg or 1.2 mg/day colchicine prophylaxis. Higher colchicine doses, and more extended early-dosing regimens over multiple hours, do not clearly add efficacy and they increase toxicity in early gout attack treatment.
Differences in Colchicine Formulations Internationally
Each country has its own labeled colchicines with different unitary dosages (0.5, 0.6, or 1 mg, scored tablet or not, with anticholinergic compound), giving the opportunity to precisely adjust the dosage. Combination of colchicine with intestinal “protector” (dicycloverine [anticholinergic], tiemonium [antispasmodic]) should not be used since this can mask diarrhea as a sign of colchicine toxicity. Examples are 1 mg Colchicine (colchicine) or 1 mg Colchimax (colchicine + opium + tiemonium methylsulfate) in France, 0.6 mg Colchrys (colchine) in the United States, and 1 mg Colchicina (colchicine) and 0.5 mg Colchimax (colchicine + dicycloverine) in Spain.
Intravenous (IV) colchicine is no longer approved in the United States and is not available in Europe. Inappropriate use and the life-threatening side effects of overdosage of IV colchicine (including deaths) were behind the FDA edict for withdrawal from the U.S. market.
Factor in Choosing Corticosteroids or ACTH (Corticotrophin) for Acute Gout
Corticosteroids have justifiably become much more popular for acute gout because of efficacy and safety in patients with contraindications to colchicine and NSAIDs, let alone low cost. Oral or parenteral steroids and intraarticular steroid injections are the most common modes of prescription. In some countries, corticotropin (ACTH) is also used and appears to be effective in many cases, with rapidity of therapeutic action seen in a matter of hours. Cost is inexpensive for ACTH in many European countries, but in the United States, it can be significant for the synthetic ACTH (which is the preferred form). Adequate, comparative controlled trials of ACTH in gout are still lacking.
Oral Therapy
Prednisone or prednisolone is a valuable frontline treatment for acute gout, with best practice guidelines to use a starting dose of at least 0.5 mg/kg prednisone on the first day. Indeed, the fact that attacks of acute gout develop in many major-organ transplant patients maintained on daily prednisone (in the range of 7.5 to 10 mg/day) is a good illustration of the need for relatively high initial doses of systemic corticosteroids to effectively treat acute gouty arthritis. Sample regimens include 30 to 60 mg prednisone daily for 3 days (depending on severity of the flare, then decreasing by 10 to 15 mg/day every 3 days until discontinuation). Alternatively, for relatively mild attacks of acute gout, a methylprednisolone single dose is sometimes used in clinical practice, but this is not an evidence-based regimen.
Two randomized, controlled, clinical trials have shown equivalence between prednisolone 30 to 35 mg/day for 5 days and full-dose NSAIDs. Prednisolone 35 mg/day for 5 days and naproxen 500 mg twice daily for 5 days were similar in efficacy and tolerance for acute gout, and prednisolone (6 doses of 30 mg over 5 days) was similar in efficacy to indomethacin (150 mg/day for 2 days followed by 75 mg/day for 3 other days) and was superior in tolerance.
Parenteral Systemic Corticosteroid Therapy
In severe cases of acute polyarticular gout or when the patient is unable to ingest oral medication, a short course of intravenous methylprednisolone appears to be an appropriate strategy. Using 100 to 150 mg IV methylprednisolone as an initial dose, followed by 50 to 75 mg twice daily for a few days, is considered to be a reasonable starting point for acute gout. A single dose of 60 mg IM triamcinolone acetonide (a potent antiinflammatory with a relatively long half-life) has been suggested to be effective for acute gout. Single intramuscular corticosteroid dose administration allows controlling drug intake, avoiding some side effects due to repeated oral steroid dosing. However, continuation with oral prednisone for several additional days after the IM triamcinolone is better clinical practice for most patients. Duration of oral corticosteroid treatment is not defined but should be limited to 5 to 14 days in order to limit side effects.
Rebound Attacks of Gout After Discontinuation of Systemic Corticosteroids
The use of corticosteroids and ACTH for treatment of acute gout attack is associated with the potential for rebound attacks when the short courses of corticosteroids are stopped. The best practice is to initiate or continue low-dose colchicine for gout-flare prophylaxis as an adjunct to therapy when systemic glucocorticoids are used to treat acute gout, particularly in the setting of recent initiation of ULT. This practice is much preferable to having to administer sustained or multiple courses of systemic corticosteroids, even at low doses, in patients with gout. Chronic steroid side effects should be monitored, including diabetes mellitus and hypertension. Concerns regarding development or increase of tophi size in corticosteroid-treated patients have been raised, but this is not yet substantiated.
Anti–Interleukin-1 Agents
Because IL-1β is the pivotal cytokine in MSU crystal–induced inflammation, development of anti–IL-1 agents, already approved in orphan autoinflammatory conditions, in the treatment and prophylaxis of acute gout will allow for addressing unmet needs. Off-label use of anakinra, a soluble IL-1 receptor antagonist, typically administered at 100 mg subcutaneously for 3 consecutive days, was linked with rapid control of pain and local symptoms within 48 hours in the majority of patients with sustained gouty arthritis in two small open reports. Moreover, rilonacept, another soluble IL-1 inhibitor, was associated with significant decrease in symptoms and decreased C-reactive protein, in a small controlled crossover study of patients with chronic gouty arthritis. This far, in clinical trials, as discussed elsewhere in this book, canakinumab was superior to 40 mg IM single-dose triamcinolone for acute gout, whereas rilonacept was not significantly superior to rilonacept and indomethacin for acute gout. In patients with comorbidities, namely chronic kidney disease (CKD) and congestive heart failure (CHF), which limit or forbid the use or the dosage of NSAIDs, anti–IL-1β agents can be helpful, under strict supervision.
Urate-Lowering Therapy and Management
Objectives
The roles of ULT are to suppress the formation and deposition of MSU crystals and to promote tophus dissolution. The main SUA targets are regularly less than 6.0 mg/dL (360 μmol/L) or less than 5.0 mg/dL (300 μmol/L). Achieving these targets is effective in controlling and remitting the disease as long as this level of urate-lowering is maintained. In cases of tophaceous gout, levels less than 250 or 300 μmol/L may be required for resolution of tophi ; the velocity of tophus size reduction appears to be linked to the lowest attained SUA levels. A mean of 20 or 29 months is required to achieve complete resolution of tophi, according to SUA of 4.0 mg/dl and 5.4 mg/dl, respectively, achieved using combined allopurinol-benzbromarone and allopurinol alone.
Ultimately, adjusted ULT prescription will prevent disease progression by reducing the body urate burden. Any patient presenting with advanced gout or demonstrating clinical tophi or recurrent attacks (two or more per year) should be treated. In Europe, it is recommended to start ULT after the first two attacks. In uncomplicated gout, ULT should be started if a second attack or further attacks occur within 1 year. Indications for ULT drug therapy are summarized in Table 16-5 , and sites of ULT action are schematized in Figure 16-5 .
Related posts:
Diagnosis of Gout
Articular Pathology of Gout, Calcium Pyrophosphate Dihydrate and Basic Calcium Phosphate Crystal Deposition Arthropathies
Gout: Epidemiology and Risk Factors
Prophylaxis of Attacks of Acute Gouty Arthritis
Basic Calcium Phosphate Crystal Arthropathy
Crystalline Disorders Associated With Renal Disease Including Oxalate Arthropathy
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