Gout is the most common form of inflammatory arthritis in the elderly. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into the transporters that handle uric acid in the kidney as well as possible links between these transporters, hyperuricemia, and hypertension. The treatment of established hyperuricemia has also seen new developments. Febuxostat and PEG-uricase are two novel treatments that have been evaluated and shown to be highly effective in the management of hyperuricemia, thus enlarging the therapeutic options available to lower uric acid levels. Monosodium urate (MSU) crystals are potent inducers of inflammation. Within the joint, they trigger a local inflammatory reaction, neutrophil recruitment, and the production of pro-inflammatory cytokines as well as other inflammatory mediators. Experimentally, the uptake of MSU crystals by monocytes involves interactions with components of the innate immune system, namely Toll-like receptor (TLR)-2, TLR-4, and CD14. Intracellularly, MSU crystals activate multiple processes that lead to the formation of the NALP-3 (NACHT, LRR, and pyrin domain-containing-3) inflammasome complex that in turn processes pro-interleukin (IL)-1 to yield mature IL-1β, which is then secreted. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances in the understanding of hyperuricemia and gout provide new therapeutic targets for the future.
To assess concordance of the management of chronic gout in UK primary care with the European League Against Rheumatism (EULAR) gout recommendations.
A postal questionnaire was sent to all adults aged >30 years registered with two general practices. Patients with possible gout attended for clinical assessment, at which the diagnosis was verified clinically. Aspects of chronic gout management, including provision of lifestyle modification advice, use of urate‐lowering therapies (ULT) including dose titration to serum urate (SUA) level, prophylaxis against acute attacks, and diuretic cessation were assessed in accordance with the EULAR recommendations.
Of 4249 (32%) completed questionnaires returned, 488 reported gout or acute attacks and were invited for clinical assessment. Of 359 attendees, 164 clinically confirmed cases of gout were identified. Advice regarding alcohol consumption was recalled by 59 (41%), weight loss by 36 (25%) and diet by 42 (29%). Allopurinol was the only ULT used and was taken by 44 (30%); 31 (70%) were taking 300 mg daily. Mean SUA was lower in allopurinol users than non‐users (318 vs 434 μmol/l) and was less often >360 μmol/l in allopurinol users (23% vs 75%). Eight patients had recently commenced allopurinol; two of these also were taking prophylactic colchicine or non‐steroidal anti‐inflammatory drugs. Of 25 patients with diuretic‐induced gout, 16 (64%) were still taking a diuretic.
Treatment of chronic gout is often suboptimal and poorly concordant with EULAR recommendations. Lifestyle advice is infrequently offered, and allopurinol is restricted to a minority. Persistent hyperuricaemia was often seen in allopurinol non‐users, but was also in allopurinol users, suggesting that doses >300 mg are often necessary.
gout; primary health care; lifestyle risk reduction; allopurinol; EULAR recommendations
Gout is a common and disabling cause of arthritis in middle-aged and elderly populations, with its main predisposing factor being hyperuricemia (serum urate > 6.8 mg/dL). Options for treatment of chronic gout until 2008 were allopurinol, a xanthine oxidase inhibitor, and the group of drugs known as uricosurics that stimulate the renal excretion of uric acid. A proportion of patients, including some with chronic kidney disease and solid organ transplantations, could not be treated with the those therapies because of intolerance, drug interactions, or adverse events. Febuxostat is a nonpurine xanthine oxidase inhibitor, recently approved in Europe and the United States for the treatment of chronic gout.
To review the clinical evidence (phase II and III studies) of the effectiveness and safety of febuxostat for treatment of hyperuricemia and gout.
Febuxostat, at doses ranging from 40 to 240 mg/day, is efficacious in reducing serum urate in patients with hyperuricemia and gout, comparing favorably with fixed doses of allopurinol in that respect. Early safety signals with respect to liver test abnormalities and cardiovascular outcomes have not been confirmed in recent large prospective trials but need to be further monitored.
Given its low cost and extensive clinical experience, allopurinol will likely remain the first-line drug for management of hyperuricemia and gout. Febuxostat may provide an important option in patients unable to use allopurinol, those with very high serum urate levels, or in the presence of refractory tophi.
febuxostat; gout; hyperuricemia; evidence
In the past few decades, the mouse has been used as a mammalian model for hyperuricemia and gout, which has increased not only in prevalence, but also in clinical complexity, accentuated in part by a dearth of novel advances in treatments for hyperuricemia and gouty arthritis. However, the use of mice for the development of gouty therapeutic drugs creates a number of problems. Thus, identification and evaluation of the therapeutic effects of chemicals in an alternative animal model is desirable. In the present study, the effects of gouty therapeutic drugs on lowering the content of uric acid and inhibiting activity of xanthine oxidase were evaluated by using a silkworm model, Bombyx mori L. (Lepidoptera: Bombycidae). The results showed that the effectiveness of oral administration of various gouty therapeutic drugs to 5th instar silkworms is consistent with results for human. The activity of xanthine oxidase of silkworm treated with allopurinol was lower, and declined in a dose-dependent manner compared with control silkworms, while sodium bicarbonate failed at inhibiting the activity of xanthine oxidase. The concentration of uric acid in the both hemolymph and fat body declined by 90 and 95% at six days post-administration with 25 mg/mL of allopurinol, respectively (p < 0.01), while the concentration of uric acid in both the hemolymph and fat body also declined by 81 and 95% at six days post-administration with 25 mg/mL of sodium bicarbonate, respectively (p < 0.01). Moreover, the epidermis of silkworm treated with allopurinol or sodium bicarbonate became transparent compared with the negative control group. These results suggest that silkworm larva can be used as an animal model for screening and evaluation of gouty therapeutic drugs.
allopurinol; gout; sodium bicarbonate; urate oxidase
The past decade has witnessed an exponential increase of novel therapeutic modalities for a variety of rheumatic disorders, including gout. During the past few years two novel therapeutic agents have been approved by the US Food and Drug Administration for the treatment of hyperuricemia in patients with gout, one of them being febuxostat, a nonpurine selective inhibitor of xanthine oxidase. Review of its pharmacokinetics and pharmacodynamics, efficacy and safety profile, and use in gout patients with comorbid conditions reveals that age and gender have no clinically significant effect and dose adjustments based on age or gender are not required. In addition, febuxostat can be used in patients with mild-to-moderate renal or hepatic involvement. Its overall efficacy and safety profile is comparable and, in certain subsets such as gout patients with mild and moderate renal insufficiency, is superior to allopurinol.
hyperuricemia; febuxostat; gout; safety profile; efficacy profile
To determine the relevance of current gout Quality indicators (QIs).
Members of the Veterans Affairs Rheumatology Consortium were invited to participate in an online survey and provide opinions (rank 0–10) regarding existing gout QIs. Opinions sought on each QI were 1) relevance to United States Veterans, 2) likelihood to improve gout care, and 3) ease of electronic capture. Participants were also asked to rank their top 3 gout QIs.
Participating VA rheumatologists were mainly male, of mean age 51.3 years and experienced in the management of gout. All 10 gout QIs were considered relevant, with a score of 8.2 of higher. The initiation of urate lowering therapy, monitoring of urate levels after initiation of urate lowering therapy, and treatment of acute gout with anti-inflammatory agents scored the highest with regards to likely to improving gout care, with the first 2 QIs also felt to be most relevant. Adjustment of initial allopurinol dosing in patients with renal impairment and in those receiving concurrent azathioprine/6-mercaptopurine were perceived as the QIs most amenable to electronic capture. The top ranked QIs were initiation of urate-lowering therapy with frequent gout attacks, serum urate monitoring after initiation of urate lowering therapy and adjustment of initial allopurinol dose to renal function.
In a national survey of VA rheumatologists, most gout QIs were thought to be highly relevant. QIs related to initiation of urate lowering therapy, serum urate monitoring, and initial dosing of allopurinol were ranked the most important for veterans with gout.
Quality Indicators; Gout; Veterans Affairs
Gout recently passed rheumatoid arthritis to become the most common inflammatory arthritis in the United States (US). However, epidemiologic studies indicate that the quality of gout management is suboptimal owing to both patient and physician issues. Only three options for urate-lowering therapy are currently available in the US: allopurinol, probenecid, and recently, febuxostat. Probenecid is generally safe except for the occurrence of urolithiasis, but is only effective for the subset of patients with better kidney function. Allopurinol use is limited due to its side effects, potential toxicity of uncertain magnitude in patients with renal disease, and failure to achieve targeted serum urate levels. In part this failure may be due to the necessity for it to be titrated for optimal therapeutic effect. Febuxostat is a new medication that may offer several advantages and can be given as an alternative to allopurinol. We review the basic biology and clinical performance of febuxostat, and consider the potential utility of this agent in comparison to the older, better-established gout therapeutics.
allopurinol; gout suppressants; nephrolithiasis; uric acid; urolithiasis
Gout is a metabolic disorder characterized by elevated uric acid levels in the body, associated with painful arthritis, tophi and nephropathy. The most frequently used pharmacologic urate lowering strategies involve reducing urate production with a xanthine oxidase inhibitor and enhancing urinary excretion of uric acid with a uricosuric agent. Urate lowering agents are limited in number, availability and effectiveness. The emergence of a new medication, febuxostat, to lower serum urate levels is welcome as no new drug have been approved since the introduction of allopurinol, in 1964, and the drugs that are available have limitations owing to inefficacy or toxicity. Febuxostat is a novel, nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.
Gout; hyperuricemia; xanthine oxidase inhibitor
Refractory gout attack is an uncommon problem, since gout flares are usually self-limited. This clinical condition is characterized by serum uric acid higher than 6 mg/Dl or continuous manifestations of recurrent flares, chronic arthritis, and increased tophi. We report in this paper a 69-year-old man with a polyarticular and protracted gout attack, despite usual treatment and low urate sera levels. In order to manage this problem, we reviewed gout pathophysiology and developed a therapeutic solution based on benzbromarone pharmacokinetics. We also review herein new options for gout treatment that could be used in similar cases.
Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than “standard dosage” allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol.
aging; febuxostat; hyperuricemia; gout; pharmacotherapy; xanthine oxidase
We sought to examine patients’ and providers’ views on the treatment of gout to better understand why management is suboptimal.
In-depth telephone interviews were conducted with gout patients (n=26) who initiated treatment with a urate-lowering drug (ULD) in the prior 6 months and with providers who care for gout patients (n=15). The interviews were audiotaped and transcribed verbatim. Using qualitative methods, results were analyzed and themes were identified. Interviews focused on the acute management, chronic management, and prevention and improvement strategies.
Providers viewed the majority of patients as having excellent relief with nonsteroidal anti-inflammatories, colchicine and glucocorticoids while some patients felt these medications were ineffective. Providers felt most patients had a good understanding of the rationale for ULD therapy and that patients responded well. Some patients felt ULDs triggered, worsened or had no impact on their disease. Most providers thought medication adherence was relatively good. Some patients reported discontinuing medications. Discontinuations were largely purposeful and due to clinical or financial concerns. Most providers thought their skills adequate to teach disease self-management behaviors. Patients requested more information and longer visit times.
Providers view gout as easily managed while patients report challenges and purposeful nonadherence.
medication use; gout treatment; medication adherence; qualitative
PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid concentration (pUAc) was 11.3 ± 2.1 mg/dl (mean ± SD). By day seven after injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had normalized in 11 subjects, whose mean pUAc decreased to 2.8 ± 2.2 mg/dl. At doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no more than 6 mg/dl. In eight subjects, plasma uricase activity was still measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other five subjects, plasma uricase activity could not be detected beyond ten days after injection; this was associated with the appearance of relatively low-titer IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were directed against PEG itself rather than the uricase protein. Three PEG antibody-positive subjects had injection-site reactions at 8 to 9 days after injection. Gout flares in six subjects were the only other significant adverse reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating life and the ability to normalize plasma uric acid in markedly hyperuricemic subjects suggest that PEG-uricase could be effective in depleting expanded tissue stores of uric acid in subjects with chronic or tophaceous gout. The development of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves further investigation, because it has potential implications for other PEGylated therapeutic agents in clinical use.
Febuxostat is a novel, potent, non-purine selective xanthine oxidase inhibitor, which in clinical trials demonstrated superior ability to lower and maintain serum urate levels below 6 mg/dL compared with conventionally used doses of allopurinol. Febuxostat was well tolerated in long term treatment in patients with hyperuricemia including those experiencing hypersensitity/intolerance to allopurinol. Dose adjustment appears unnecessary in patients with mild to moderate renal or liver insufficiency or advanced age. The most common adverse reactions reported were abnormal liver function tests, headache, and gastrointestinal symptoms, which were usually mild and transient. However, whether hepatotoxicity becomes a limitation in the use of febuxostat needs to be determined in further studies. An increased frequency of gout flares occurs for a prolonged period after treatment initiation, as with any aggressive lowering of serum urate, and prolonged prophylaxis with colchicine or NSAIDs is usually required. Febuxostat has been granted marketing authorization by the European Commission in early 2008 for the treatment of chronic hyperuricemia and gout. Febuxostat is the first major treatment alternative for gout in more than 40 years and is a promising alternative to allopurinol, although continued long-term surveillance on safety and efficacy is required.
febuxostat; TEI-6720; TMX-67; gout; hyperuricemia; xanthine oxidase inhibitor
This is a case report of a patient with treatment resistant gout who was prescribed pegloticase and developed a severe reaction. A 30-year-old Hawaiian-Filipino man presented with a nine-year history of gout that progressed from episodic monoarticular arthritis, treated with aspiration and corticosteroid injections, to more aggressive disease with more frequent attacks requiring escalation of therapy. He was treated with systemic corticosteroids, colchicine and nonsteroidal anti-inflammatory drugs, but then required allopurinol. Despite aggressive therapy, the patient continued to have hyperuricemia and tophi developed even after treatment with febuxostat and probenicid. The patient became wheel chair bound due to his pain and, at that point, the decision was made to initiate treatment with pegloticase. The patient initially experienced significant improvement with treatment; however, he soon began to have elevation in his serum uric acid levels and developed a severe reaction during treatment.
pegloticase; tophi; treatment resistant gout; infusion reaction
Purpose of review
Growing awareness of patients with refractory gout is prompting a reassessment of treatment strategy. This article reviews the current practice of targeting serum urate concentrations (sUA) in the mid-normal range (roughly 4–6 mg/dL), and considers the rationale for more aggressively lowering sUA in patients with poorly controlled chronic gout. Some hypothetical concerns with inducing hypouricemia are considered, and relevant clinical evidence is evaluated.
Recent studies confirm the benefits of modestly reducing sUA in many gout patients. However, tophi and tissue stores of monosodium urate crystals resolve slowly, particularly in patients with longstanding disease. Consistent with physicochemical principles, the rate of decrease in tophus size increases with a reduction in sUA concentration over a broad range. Reducing sUA to near or below 2 mg/dL can be achieved in some patients with current urate lowering drugs, but new drugs now under investigation may be more effective. As a free radical scavenger, uric acid has been postulated to protect from oxidative stress. However, inherited disorders associated with profound, lifelong hypouricemia indicate that maintaining sUA near or below 2 mg/dL would probably be safe.
Targeting low sUA could improve the elimination of tissue urate stores and achieve better control of disease in patients with refractory gout.
Gout; tophus; hypouricemia; pegloticase; febuxostat
To develop evidence based recommendations for the management of gout.
The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions on management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat, relative risk, odds ratio, and incremental cost‐effectiveness ratio were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales.
12 key propositions were generated after three Delphi rounds. Propositions included both non‐pharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT), and prophylaxis of acute attacks. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low animal purine diet) and treatment of associated comorbidity and risk factors were emphasised. Recommended drugs for acute attacks were oral non‐steroidal anti‐inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout. Allopurinol was confirmed as effective long term ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 to 2.24)) and can be used in patients with mild to moderate renal insufficiency but may be hepatotoxic. When gout is associated with the use of diuretics, the diuretic should be stopped if possible. For prophylaxis against acute attacks, either colchicine 0.5–1 mg daily or an NSAID (with gastroprotection if indicated) are recommended.
12 key recommendations for management of gout were developed, using a combination of research based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition.
EULAR; gout; guidelines; treatment
Hyperuricemia is a feature of several pathologies and requires an appropriate and often early treatment, owing to the severe consequences that it may cause. A rapid and massive raise of uric acid, during tumor lysis syndrome (TLS), and also a lower and chronic hyperuricemia, as in gout, mainly damage the kidney. To prevent or treat these consequences, a new therapeutic option is represented by rasburicase, a recombinant form of an enzyme, urate oxidase. This enzyme converts hypoxanthine and xanthine into allantoin, a more soluble molecule, easily cleared by kidney. The several types of urate oxidase have followed each other, with progressive reduction of adverse reactions. The most important among them are allergenicity and the development of antibodies which compromise their effectiveness. Nevertheless, a limit of rasburicase's use remains its cost, which obliges to a judicious choice to prevent TLS in high risk patients with cancer and in case of allergy or impossibility to take allopurinol orally both in TLS and in gout. A large body of evidence confirms the efficacy and safety of rasburicase, even in comparison to the standard drugs used in the aforementioned pathologies.
Urate oxidase; allantoin; rasburicase; hyperuricemia; tumor lysis syndrome; acute renal failure; gout; allopurinol; uric acid
Gout is an inflammatory arthritis characterized by abrupt self-limiting attacks of inflammation caused by precipitation of monosodium urate crystals (MSU) in the joint. Recent studies suggest that orchestration of the MSU-induced inflammatory response is dependent on the proinflammatory cytokine IL-1β, underlined by promising results in early IL-1 inhibitor trials in gout patients. This IL-1-dependent innate inflammatory phenotype, which is observed in a number of diseases in addition to gout, is now understood to rely on the formation of the macromolecular NLRP3 inflammasome complex in response to the MSU ‘danger signal’. This review focuses on our current understanding of the NLRP3 inflammasome and its critical role in MSU-crystal induced inflammatory gout attacks. It also discusses the management of treatment-resistant acute and chronic tophaceous gout with IL-1 inhibitors; early clinical studies of rilonacept (IL-1 Trap), canakinumab (monoclonal anti-IL-1β antibody), and anakinra have all demonstrated treatment efficacy in such patients.
gout; inflammasome; NLRP3; IL-1
The prevalence of gout is increasing with increased life expectancy. Approximately half of the patients with gout have some degree of renal impairment. If both conditions persistently coexist, and in severe tophaceous gout, in particular, treatment has been difficult. We here report on the case of an 87-year-old woman, who had been suffering from recurrent gouty arthritis over 4 years. Monthly polyarthritis attacks were accompanied by subcutaneous tophi. Serum uric acid levels were constantly above 600 μmol/L (10 mg/dL). Allopurinol was no option because of intolerance, while benzbromarone was ineffective because of renal impairment. Therefore, the novel xanthin oxidase inhibitor febuxostat was started, achieving rapid control of serum urate levels (<360 μmol/L). After initial worsening of inflammation in the first weeks, gouty attacks stopped and all tophi resolved within the following 10 months. Renal function remained stable.
An association between high levels of serum urate and cardiovascular disease has been proposed for many decades. However, it was only recently that compelling basic science data, small clinical trials, and epidemiological studies have provided support to the idea of a true causal effect. In this review we present recently published data that study the association between hyperuricemia and selected cardiovascular diseases, with a final conclusion about the possibility of this association being causal.
Gout is a common inflammatory arthritis caused by articular precipitation of monosodium urate crystals. It usually affects the first metatarsophalangeal joint of the foot and less commonly other joints, such as wrists, elbows, knees and ankles.
We report the case of a 75-year-old Caucasian man with tophaceous multiarticular gout, soft-tissue involvement and ulcerated tophi on the first metatarsophalangeal joint of the left foot, on the first interphalangeal joint of the right foot and on the left thumb.
Ulcers due to tophaceous gout are currently uncommon considering the positive effect of pharmaceutical treatment in controlling hyperuricemia. Surgical treatment is seldom required for gout and is usually reserved for cases of recurrent attacks with deformities, severe pain, infection and joint destruction.
Recent studies have confirmed that gout is an inborn error of metabolism. It has now become evident that the hyperuricemia associated with gout might occur either due to overproduction of uric acid, underexcretion of uric acid or a combination of these processes. Furthermore, patients with excessive purine synthesis may have a specific enzyme defect resulting in altered feedback inhibition of purine synthesis. A neurological disease manifest by mental retardation, choreo-athetosis, aggressive behavior, lip-biting and self-mutilation and associated with decidedly increased purine biosynthesis serves as a prototype of this kind of disorder. Other defects in regulation of purine biosynthesis have been postulated but their existence not yet confirmed.
It has been demonstrated that urate crystals which are deposited from hyperuricemic body fluids set up an acute inflammatory reaction by means of a variety of chemical mediators. Thus, acute gouty arthritis is now recognized as an example of “crystal induced” synovitis.
The treatment of gout consists of (1) the control of acute gouty attacks, and (2) the maintenance of normal serum uric acid concentrations. This latter may be achieved either with uricosuric drugs or with xanthine oxidase inhibition. With these principles in mind, it is now possible to avoid many of the severe crippling effects of gout and to restore the vast majority of gouty patients to useful and productive lives.
To identify gaps in therapy with urate-lowering drugs for the treatment of gout as well as factors associated with resuming therapy.
We identified persons from two integrated delivery systems 18 years or older with a diagnosis of gout who initiated use of a urate-lowering drug from January 1, 2000 through June 30, 2006 and who had a gap in therapy. A gap was defined as a period of over 60 days after the completion of one prescription in which no refill for a urate-lowering drug was obtained. Survival curves were used to assess return to therapy of urate-lowering drugs. Cox proportional hazards analysis estimated the association between covariates and return to therapy.
There were 4,166 new users of urate-lowering drugs (97% received allopurinol) of whom 2,929 (70%) had a gap in therapy. Among those with a gap, in 75% it occurred in the first year of therapy. Fifty percent of patients with a gap returned to therapy within 8 months, and by 4 years it was 75%. Age 45 to 74 (<45 referent) and greater duration of urate-lowering drug use prior to the gap was associated with resuming treatment within one year. In contrast, receipt of NSAIDs or glucocorticoids in the year prior to the gap was associated with a reduced likelihood of resuming therapy.
The majority of gout patients with gaps in urate-lowering drug use returned to treatment. More investigation is needed to better understand why patients may go for months without refilling prescriptions given the clinical consequences of nonadherence.
persistence; adherence; compliance; gout; urate lowering drugs
Little is known about the characteristics, evaluation and treatment of women with gout.
To examine the epidemiological differences and differences in treatment between men and women in a large patient population.
The data from approximately 1.4 million people who were members of seven managed care plans in the USA for at least 1 year between 1 January 1999 and 31 December 2003 were examined. Adult members who had pharmacy benefits and at least two ambulatory claims specifying a diagnosis of gout were identified. In addition, men and women who were new users of urate‐lowering drugs (ULDs) were identified to assess adherence with recommended surveillance of serum urate levels within 6 months of initiating urate‐lowering treatment.
A total of 6133 people (4975 men and 1158 women) with two or more International Classification of Disease‐9 codes for gout were identified. As compared with men with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of new users of urate‐lowering treatment had appropriate surveillance of serum urate levels post‐initiation of urate‐lowering treatment. After controlling for age, comorbidities, gout treatments, number of ULD dispensings and health plan, women were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to receive the recommended serum urate level testing.
Women with gout were older, had greater comorbidities and more often used diuretics and received appropriate surveillance of serum urate levels, suggesting that the factors leading to gout as well as monitoring of treatment are very different in women and men.
Gout affects more than 1% of adults in the USA, and it is the most common form of inflammatory arthritis among men. Accumulating data support an increase in the prevalence of gout that is potentially attributable to recent shifts in diet and lifestyle, improved medical care, and increased longevity. There are both nonmodifiable and modifiable risk factors for hyperuricemia and gout. Nonmodifiable risk factors include age and sex. Gout prevalence increases in direct association with age; the increased longevity of populations in industrialized nations may contribute to a higher prevalence of gout through the disorder's association with aging-related diseases such as metabolic syndrome and hypertension, and treatments for these diseases such as thiazide diuretics for hypertension. Although gout is considered to be primarily a male disease, there is a more equal sex distribution among elderly patients. Modifiable risk factors for gout include obesity, the use of certain medications, high purine intake, and consumption of purine-rich alcoholic beverages. The increasing prevalence of gout worldwide indicates that there is an urgent need for improved efforts to identify patients with hyperuricemia early in the disease process, before the clinical manifestations of gout become apparent.