A Review of Hyperuricaemia Management with Febuxostat: Dosage Titration, Monitoring and Maintenance

1. Head, Department of Nephrology and Transplantation, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India. 2. Chief Cardiologist, Department of Cardiology, PRS Hospital, Trivandum, Kerala, India. 3. Head, Department of Cardiology, Dr. Dargad Clinic, Mukund Nagar, Mumbai, Maharashtra, India. 4. Endocrinologist, Department of Endocrinology, Medicare Nursing Home, Gandhi Nagar, Jammu and Kashmir, India.

Abstract

The burden of hyperuricaemia has been steadily increasing both globally and in India. The increasing number of hyperuricaemia-associated co-morbidities, such as Chronic Kidney Disease (CKD), Type 2 Diabetes Mellitus (T2DM), Cardiovascular Diseases (CVD), and hypertension, implies that hyperuricaemia is associated with an increased risk of other chronic conditions or diseases. Despite the availability of several guidelines on hyperuricaemia, recommendations for appropriate titration of Urate Lowering Therapy (ULT) to achieve and maintain appropriate serum Uric Acid (sUA) levels in the Indian context are unclear. Another important challenge is the diagnosis and management of asymptomatic hyperuricaemia with ULT. This review summarises evidence-based discussion and review of literature by expert panellists on hyperuricaemia management with ULT, particularly with Xanthine Oxidase (XO) inhibitors. Based on the discussion, the experts developed a dose-titration algorithm for initiation and long-term management of hyperuricaemia with ULT, comprising febuxostat. The review also highlights some of the current challenges in hyperuricaemia management, which when addressed would benefit primary care physicians across the country for early screening and timely management of hyperuricaemia.

Allopurinol, Awareness, Renal impairment, Serum uric acid, Urate lowering therapy

The burden of hyperuricaemia has been on the rise both globally and in India (1). Hyperuricaemia or increased serum Uric Acid (sUA) levels results from either overproduction of uric acid (an end product of purine metabolism) or its underexcretion (2). Hyperuricaemia is defined as sUA levels >7 mg/dL in men and >6 mg/dL in women (1). In the intracellular setting, uric acid has proinflammatory effects, whereas it acts as a strong antioxidant in the plasma. Prolonged duration of hyperuricaemia leads to a chronic phase of microvascular injury, which contributes to afferent arteriolopathy. This results in elevated blood pressure and unresponsiveness to Urate Lowering Therapy (ULT) over time (3). Besides hypertension, increased levels of sUA have been associated with an increased risk of multiple disorders, including hypertension, Chronic Kidney Disease (CKD), Type 2 Diabetes Mellitus (T2DM), stroke, Congestive Heart Failure (CHF), Coronary Artery Disease (CAD), metabolic syndrome, dyslipidaemia, atherosclerosis, and obesity (2).

Additionally, hyperuricaemia is an independent risk factor for renal disorders and CVDs (4). Hyperuricaemia can be symptomatic or asymptomatic. In asymptomatic hyperuricaemia, the sUA level is elevated without any symptoms, while in symptomatic patients elevated sUA levels are accompanied by gout, acute urate nephropathy, or urolithiasis (5). Despite the association between hyperuricaemia and multiple co-morbidities, there still exist considerable gaps in the approach toward hyperuricaemia screening and management. Common gaps included entifying the threshold sUA level for initiating ULT, management of asymptomatic patients, routine screening for sUA, and use of sUA as a prognostic tool in clinical screening (5). With this background, a series of multidisciplinary advisory board meetings were conducted with experts from different specialties across four zones of India to gain expert insights on hyperuricaemia management with ULT, understand the prevailing practices on titration of ULT in India, develop a simplified algorithm for treatment initiation, titration and maintenance with ULT, and address the current gaps and challenges in hyperuricaemia management.

BURDEN OF HYPERURICAEMIA

Epidemiology of Hyperuricaemia

The prevalence of hyperuricaemia is higher in Asian countries, including India (25.8%), when compared with that in western countries like the United States of America (USA) (21-22%), Italy (9-12%), and Brazil (13%) (1). In India, as compared to healthy individuals, higher prevalence of hyperuricaemia has been noted in patients with co-morbidities, such as hypertension (37.3%), T2DM (25.3%), obesity (44.6%), and metabolic syndrome (47.1%) (2). High sUA levels have also been reported in 38.4% of individuals with CKD (6). Further, as compared to patients with T2DM (5.6%) or hypertension (4.2%) alone, the incidence of hyperuricaemia is higher in patients with both T2DM and hypertension (7.4%) (1). In the Indian population, the prevalence of hyperuricaemia increases with age and duration of co-morbidity and is higher in men as compared to women (1). Furthermore, compared to urban areas, sUA levels are higher in the rural areas (7).

Hyperuricaemia and Associated Co-morbidities

Previously, hyperuricaemia was considered as an independent condition or a consequence of the co-morbidities in persons with T2DM, Heart failure (HF), hypertension, obesity, or CVD. However, accumulating evidence suggests that rather than being just an inducer of gout, hyperuricaemia might have different clinical implications in individuals with these co-morbidities (8). Apart from these co-morbidities, high sUA levels are also associated with male sex, smoking, oldage, dyslipidaemia, obesity, increased waist-hip ratio, hypertriglyceridemia, and metabolic syndrome (9). (Table/Fig 1) depicts the different co-morbidities for which hyperuricaemia is proposed to be a predictive factor (10).

1. Chronic Kidney Disease (CKD): In individuals with CKD, sUA levels are elevated owing to decreased estimated Glomerular Filtration Rate (eGFR) (8). Several studies have elucidated a close association between hyperuricaemia and kidney diseases (4). In fact, hyperuricaemia is considered to be an independent risk factor for the development of CKD, diabetic nephropathy, Acute Kidney Injury (AKI), and End-Stage Kidney Disease (ESKD). The existing findings on the role of sUA in CKD progression are inconsistent, there is insufficient evidence to suggest that lowering sUA levels prevents CKD progression (4),(11),(12),(13),(14), and the causal relationship is yet to be proven with longitudinal studies (4). A few observational studies support the association of hyperuricaemia with the risk of CKD development or progression in persons with T2DM (15),(16). A meta-analysis of 24 studies, involving 25,453 CKD patients, found a significant association between high sUA levels and risk of mortality (17). In patients with ESKD undergoing haemodialysis, hyperuricaemia was a predictor of higher mortality risk (18).

A study from South India reported a significantly higher prevalence of hyperuricaemia in patients with CKD versus those without CKD (mean sUA levels 8.0 mg/dL and 5.03 mg/dL in CKD and non CKD groups, p-value <0.001). Among CKD patients, sUA levels were higher in diabetic and hypertensive patients, and prevalence of CAD was also higher in CKD patients with high sUA levels (19).

Hyperuricaemia is also frequently observed in renal transplant patients. Lower eGFR levels following transplantation are associated with increased sUA levels. Reportedly, hyperuricaemia does not cause increased mortality or graft loss in renal transplant patients (8).

2. Diabetes: Hyperuricaemia has emerged as an independent risk factor for the development of T2DM (20). Multiple meta-analyses have revealed that 1 mg/dL increase in sUA level was associated with 6-17% increase in the risk of T2DM (21),(22). Higher concentrations of serum insulin cause increased renal reabsorption of uric acid, thereby increasing sUA levels (23). While several studies have provided observational evidence that elevated sUA levels lead to the development of diabetes (22),(24), some conflicting studies suggest inverse association between diabetes and sUA levels (25). In individuals with normoglycaemia, higher sUA levels have been associated with a higher risk of incident prediabetes (26),(27).

Patients with T2DM and hyperuricaemia, with decreased urinary excretion of uric acid, are reportedly at higher risk of developing CKD; the prevalence is as high as 47.8% (28). However, the causal relationship between diabetes and hyperuricaemia is still inconclusive (29). A recent study in a mouse model demonstrated that hyperuricaemia does not induce diabetes but predisposes to diabetes by disrupting beta-cell function. The study showed that hyperuricaemia-induced inhibition of islet-beta-cell survival accelerates diabetes (29).

3. Hypertension: A plethora of clinical studies have demonstrated that sUA is an independent predictor of hypertension (30). Among untreated hypertensive patients, approximately 25-40% have concomitant hyperuricaemia (31). The findings of a hyperuricaemia screening program from India revealed that 35.1% of hyperuricaemic patients were hypertensive (2). A retrospective study from North India reported hyperuricaemia prevalence of 35.3% among patients with hypertension and/or T2DM (32).

A study showed that in the general population untreated for both hypertension and hyperuricaemia, every 1 mg/dL increase in sUA level contributed to 20% increase in the prevalence of hypertension (31),(33). Asymptomatic hyperuricaemia in the absence of any co-morbidities can also predict the development of hypertension (34).

Several antihypertensive medications also affect sUA levels. While antihypertensive agents like beta-blockers, thiazide diuretics, angiotensin II receptor antagonists, and angiotensin-converting enzyme inhibitors often increase sUA levels, long-acting calcium antagonists and losartan have been shown to decrease sUA levels (31).

4. Cardiovascular disorders: Hyperuricaemia directly or indirectly promotes the progression of cardiometabolic risk factors involved in the pathogenesis of CVD, including HF. Baseline sUA levels serve as a predictor of Cardiovascular (CV) mortality (35). The development and progression of cardiovascular disorders, such as Coronary Heart Disease (CHD), stroke, myocardial infarction, HF, hypertension, and CVD, have been associated with elevated sUA levels (35),(36). Elevated sUA levels are also a predictor of all-cause mortality among HF patients. In the general population, higher sUA levels are a predictor of all-cause or CV mortality (35). Hyperuricaemia is proposed to an independent risk factor or a significant marker for ischaemic heart disease (37). An observational cross-sectional study from East India reported 42.7% prevalence of hyperuricaemia among 82 patients with CAD (38). Another study from South India reported 46.5% prevalence of hyperuricaemia among 520 patients with stable CAD (9).

PATHOPHYSIOLOGICAL MECHANISMS OF HYPERURICAEMIA AND VARIOUS
CO-MORBIDITIES

Hyperuricaemia and Hypertension

Two phases are involved in the pathophysiology of hyperuricaemia and hypertension: an initial acute phase involving endothelial dysfunction, inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system; and a later chronic phase involving arterial wall hypertrophy, which causes interstitial inflammation and renal microvascular changes (30).

Hyperuricaemia and CKD

High intracellular uric acid levels induce a pro-oxidant environment that activates profibrotic, proinflammatory, proliferative and senescence pathways. It causes endothelial dysfunction and secretion of vasoconstrictors. These mechanisms lead to systemic hypertension and CKD (39).

Hyperuricaemia and Diabetes

The pathological mechanisms include inflammation with increased levels of Tumour Necrosis Factor-α (TNF-α), Nuclear Factor Kappa light chain enhancer of activated B cells (NF-kB), C-Reactive Protein (CRP) and Interleukin-6 (IL-6); oxidative stress involving increased Reactive Oxygen Species (ROS) production; endothelial dysfunction involving reduced bioavailability of Nitric Oxide (NO); and inhibition of the trigger of the insulin signalling pathway involving Ectonucleotide Pyrophosphatase Phosphodiesterase-1 (ENPP1) recruitment at the receptor level. The mechanisms associated with the chronic complications of diabetes include promoting vascular thrombosis by triggering platelet adhesion and aggregation; and activation of the Renin-Angiotensin-Aldosterone System (RAAS) system via increased production of juxtaglomerular renin and plasma angiotensin II induced aldosterone release (which is mediated by hyperuricaemia-induced ROS). The activation of RAAS leads to inflammation, vascular dysfunction, renal and cardiovascular complications, and high intraglomerular pressure (40).

Hyperuricaemia and Cardiovascular Disorders

Atherosclerosis causes CHD. High uric acid levels cause atherosclerosis via endothelial dysfunction, platelet activation, ROS production, and low-density lipoprotein oxidation. Atrial fibrillation is caused by hyperuricaemia-induced inflammation and oxidative stress. High uric acid levels are directly associated with increase in left atrial diameter, which leads to atrial fibrillation and thrombosis. High uric acid-induced oxidative stress, inflammation and myocardial hypertrophy are the key mediators in development and progression of HF (41).

The proposed pathophysiological mechanisms underlying high uric acid-induced co-morbidities are delineated in (Table/Fig 2).

SCREENING FOR HYPERURICAEMIA

Early screening of sUA levels has been advised by the Indian Forum of Hyperuricaemia (IFH), even in asymptomatic patients to prevent or manage the complications of hyperuricaemia in patients with co-morbidities such as T2DM, prediabetes, CVD, and metabolic syndrome (42). The British Society for Rheumatology 2017 guidelines recommend that all patients with gout should be screened for co-morbid conditions, such as diabetes, hypertension, dyslipidaemia, renal disease, obesity, cigarette smoking, and CV risk factors, due to the association of these co-morbidities with gout (43).

However, as per the Integrated Diabetes and Endocrine Academy (IDEA) consensus statement on the management of asymptomatic hyperuricaemia, routine screening for hyperuricaemia is not recommended because the natural course of asymptomatic hyperuricaemia is not well understood (44). Therefore, screening for hyperuricaemia has been recommended by IDEA only for patients with:

• CVD
• Metabolic syndrome
• CKD (eGFR ≤60 mL/min/1.73 m²)
• Malignancy, particularly when receiving chemotherapy
• History of medications that induce hyperuricaemia, such as diuretics (loop and thiazide diuretics), antitubercular drugs (pyrazinamide and ethambutol), low-dose aspirin (≤325 mg/day), immunosuppressants (cyclosporine and tacrolimus), chemotherapeutic agents for tumour lysis syndrome, nicotinic acid, testosterone, and levodopa
• History of acute monoarthritis suggestive of gout
• Urolithiasis
• History of chronic gout or tophi

In addition to the above-mentioned patient populations, the experts opined that screening for hyperuricaemia among pre-hypertensive individuals is also important because hyperuricaemia is a strong risk predictor of development of hypertension in these patients. All the global and national guidelines univocally and strongly recommend screening for hyperuricemia in individuals with co-morbidities (45).

MANAGEMENT

Indian Guidelines on Hyperuricaemia Management

Persistent untreated asymptomatic hyperuricaemia may lead to complications like nephrolithiasis, urate nephropathy, and gout. Asymptomatic hyperuricaemia is also noted in patients with CKD, hypertension, CVD, and metabolic syndrome (42). Previously, there were no specific guidelines on hyperuricaemia in India, especially for the management of asymptomatic hyperuricaemia (44).

Global societies such as the American College of Rheumatology (ACR) and the British Society for Rheumatology (BSR) do not have guidelines providing specific recommendations for the management of asymptomatic hyperuricaemia [43,46]. In order to fill these lacunae, IDEA developed consensus recommendations for the management of asymptomatic hyperuricaemia in 2020 (44).

The IFH was formed to provide a clear definition of hyperuricaemia, delineate treatment options for hyperuricemic patients, and to establish hyperuricaemia as a risk factor for the development of various co-morbidities (42). A simplified algorithm on hyperuricaemia management, based on IFH (42) and IDEA (44) recommendations is presented in (Table/Fig 3).

Management of chronic hyperuricaemia involves long-term maintenance of uric acid level below <6 mg/dL, whereby the formation of new urate crystals is prevented, and the existing crystals are dissolved. Besides lifestyle modifications and pharmacotherapy, chronic hyperuricaemia management should encompass multiple steps as presented in (Table/Fig 4) (42).

Although hyperuricaemia screening and treatment can be carried out at a low cost, indiscriminate hyperuricaemia screening should be avoided, while ULT therapy should be individualised for each patient (44).

Hyperuricaemia Management with ULT

Dosage titration, monitoring, and maintenance: Xanthine oxidase (XO) inhibitors (allopurinol and febuxostat), uricosurics (probenecid and benzbromarone), and uricase or urate oxidase (pegloticase, rasburicase) are some of the urate-lowering drugs commonly advised for the management of hyperuricaemia (42).

Allopurinol is the relatively older XO inhibitor. The usual initiation dose of allopurinol is ≤100 mg/day. It has been associated with hypersensitivity reactions including potentially life-threatening drug reactions, Stevens-Johnson syndrome, rash, cytopenia, pruritus, and toxic epidermolysis (5). In patients with pre-existing renal insufficiency, allopurinol may cause progression of renal failure becauseit undergoes renal clearance. To prevent life-threatening toxicity, allopurinol should be used in reduced doses in patients with eGFR <60 mL/min/1.73m² [5,47].

Febuxostat is the newer XO inhibitor with better efficacy than allopurinol. It is primarily cleared by the liver and bile and is associated with lesser risk of hypersensitivity as compared to allopurinol (47). The recommended starting dose of febuxostat is 40-80 mg/day (5). Febuxostat can be used without dose reduction in CKD patients with eGFR ≥30 mL/min/1.73 m², and hence is preferred in patients with renal insufficiency [5,46]. Although allopurinol has been the cornerstone ULT for decades, febuxostat has emerged as the more potent ULT (48).

Uricosurics like benzbromarone and probenecid lower sUA levels by increasing urate excretion. However, benzbromarone has been withdrawn from several countries because of abnormal liver function or mortality from liver failure associated with its use (42). Uricases, such as pegloticase and rasburicase, lower sUA by converting it to allantoin, which is 5-10 times more urine-soluble than uric acid. Although these agents have significant urate-lowering efficacy, pegloticase has been associated with cardiovascular side effects. Rasburi case is associated with significant adverse effects, including anaphylactic reactions, skin rashes, and methemoglobinemia (42).

A comparison of different types of ULT has been presented in (Table/Fig 5) (42).

Initiation of ULT: Before initiating ULT, the effects of lifestyle or sUA elevating drugs should be ruled out [42,43]. In case of presence of renal stones or CKD stage ≥3 (or eGFR is <60 mL/min/1.73 m²), ULT should be initiated when sUA levels are >7 mg/dL (44). In global guidelines, allopurinol is the commonly recommended first-line ULT. The initiation dose for allopurinol is 50-100 mg once daily (43). It is strongly recommended for all patients by the ACR guidelines, even in those with moderate-to-severe CKD (stage 3 or higher) (46). Use of febuxostat is recommended as an alternative ULT when allopurinol is not tolerated or it isadded to allopurinol when dose escalation is contraindicated due to presence of renal impairment [43,49]. The IDEA consensus guidelines recommend using febuxostat as first-line therapy in patients with CKD (44). The BSR recommends initiating febuxostat at a dose of 80 mg once daily, while ACR recommends ≤40 mg dose for initiation [43,46]. The efficacy of 40-120 mg of febuxostat is similar to that of 300 mg dose of allopurinol (42). Owing to the increased risk of adverse reactions with allopurinol and the subsequent requirement of dose modification, febuxostat may be preferred for stage 3-4 CKD patients (44).

Dose titration for ULT: For all patients receiving ULT, achieving and maintaining a target sUA level of <6 mg/dL is strongly recommended by the ACR (46). While sUA levels should be maintained below the target, dose titration involves both up- and down- titration of ULT doses because severe decline in sUA levels (to <3 mg/dL) is also not advisable (44). After initiation with low-dose (50-100 mg) allopurinol, the dose should be uptitrated in increments of 100 mg approximately once every four weeks till the target sUA level is reached (43). Up-titration of allopurinol can be done up to the FDA-approved maximum dose of 800 mg daily [43,46]. The increments should be smaller for patients with renal impairment (about 50 mg) (43). In case of febuxostat, up-titration is recommended after four weeks to a maximum dose of 120 mg daily till target sUA levels are reached (43). Clinical studies that evaluated different titration doses of febuxostat have reported that the dose of febuxostat can be down-titrated from 80 mg/day to 60 mg/day, 40 mg/day or 20 mg/day as per the requirement [50-55].

Monitoring of patients on ULT: After dose titration of ULT, sUA levels should be monitored monthly or once in two months [42,56]. Sustained low levels of sUA are necessary for some important physiological roles, such as neuroprotection. Hence, the sUA levels should be closely monitored to avoid decline below the targeted range (<3 mg/dL) (5). Patients should be monitored till target sUA levels are maintained, and stable condition is achieved [42,55,56]. ULT can be temporarily discontinued if sUA level drops below 3 mg/dL (57).

Maintenance therapy with urate lowering agents: There is no clarity in the existing guidelines regarding the maintenance of sUA levels within the desired range (6-3 mg/dL) with ULT in symptomatic hyperuricaemia patients. Once the target sUA levels are reached, a low and constant maintenance dose could be used to maintain sUA levels within a desired range. Maintenance therapy with urate-lowering agents would be beneficial because to avoid gout flares, discontinuation of ULT is not recommended after target sUA levels are achieved (46). After target sUA levels and stable disease status are achieved, the patient should be continued on the same dose of ULT or maintained on low-dose therapy and reviewed once in 6 to 12 months [42,55,56]. If target sUA level is not maintained, dose of the ULT should be adjusted (42). ULT should be continued indefinitely at the maintenance dose, unless modifiable risk factors are successfully addressed, and clinical cure is achieved [43,46,55].

Simplified algorithm for dosage titration, monitoring and long-term maintenance of hyperuricaemia with ULT: For allopurinol, the treatment algorithm is nearly consistent across all global and national guidelines suggesting initiation of allopurinol at a dose of 100 mg/day. Periodic monitoring (once every 2-4 weeks) is recommended, and the dosage can be increased by 50-100 mg/day, to achieve target sUA levels (42). In case of febuxostat, the IFH recommends treatment initiation with 40 mg/day, which can be up-titrated to 120 mg/day, if necessary (42). However, there is lack of clarity on the down-titration with febuxostat after target sUA level is reached. Temporary discontinuation of ULT is not advisable since because it increases the likelihood of flares (46), while continuation of unaltered therapy might lower the sUA levels below the physiological range (<3 mg/dL), which is not desirable (5).

Several studies with lower doses of febuxostat showed similar efficacy and safety as allopurinol (Table/Fig 6) [51-54,58,59]. Down-titration of febuxostat to low doses, such as 20 mg/day, might aid maintenance of therapy without the concern of undesired lowering of sUA levels or flares. Based on the review of current literature and existing guidelines, the experts developed the following algorithm on hyperuricaemia management with febuxostat, delineating the details of frequency of monitoring, titration doses and maintenance therapy (Table/Fig 7).

Safety of urate-lowering drugs: The active metabolite of allopurinol, oxypurinol, undergoes renal excretion and gets accumulated in patients with renal impairment leading to complications, thereby necessitating dose reductions (42). Although several clinical studies have demonstrated the benefits of allopurinol in patients with co-morbidities (44), allopurinol therapy is associated with serious adverse effects including rash, gastrointestinal effects, and Stevens-Johnson syndrome. Another rare and potentially lethal adverse effect of allopurinol is allopurinol hypersensitivity syndrome (AHS). Further, allopurinol interacts with multiple drugs including amoxicillin and ampicillin, which can cause skin rashes (42). Use of allopurinol is known to be problematic in the elderly population and in those with HLA-B*5801 antigen thatprimarily comprise the Asian population (48).

The common side-effects associated with febuxostat are nausea, diarrhoea, and elevated levels of liver enzymes. However, the incidence of side effects with febuxostat has been found to be low even at high doses (≥120 mg). Notably, the sides effects associated with febuxostat are not affected by age and impaired liver or renal function. Very few medications are known to interact with febuxostat, such as azathioprine (42).

Cardiovascular safety of febuxostat versus allopurinol: The findings of the cardiovascular safety of febuxostat and allopurinol in patients with gout and cardiovascular morbidities (CARES) trial showed numerically higher all-cause and CV mortality with febuxostat as compared to allopurinol (60). These findings resulted inthe issue of a “black box” warning by the FDA on the risk of CV death withfebuxostat use in patients with pre-existing CVD (48). Subsequently, a population-based cohort study showed that there was no difference in the risk of all-cause mortality and CV events between gout patients (aged ≥65 years) initiated on febuxostat versus allopurinol [61]. A meta-analysis, involving 10 RCTs and 14,402 subjects, evaluated the risk of Major Adverse Cardiovascular Events (MACE) in gout and hyperuricaemia patients using febuxostat. Nine out of these ten RCTs included subjects with a prior history of either CAD and HF, or hypertension. The findings revealed that febuxostat did not affect the risk of MACE but increased the risk of CV death (p-value=0.03) [62].

Recently published results of the randomised non inferiority Febuxostat versus Allopurinol Streamlined Trial (FAST) trial involving 6128 gout patients with previous CVD established that febuxostat (80-120 mg once daily) was non inferior to allopurinol (100-900 mg once daily) in terms of primary CV endpoints. Further, long-term use of febuxostat was not associated with serious adverse events or an increased risk of death compared to allopurinol [63]. The regulatory warnings may need to be relooked into based on these recent findings about febuxostat use in patients with CVD [63].

Duration of Urate Lowering Therapy (ULT): Hyperuricaemia is termed as primary if it is associated with any underlying cause and secondary if no underlying cause leading to hyperuricaemia can be identified [64]. Duration of ULT is markedly different for primary and secondary hyperuricaemia. While for primary hyperuricaemia, ULT should be continued indefinitely, in case of secondary hyperuricaemia, ULT may be discontinued once stable sUA level is achieved and the underlying risk factor for hyperuricaemia is addressed (43).

HYPERURICAEMIA AWARENESS

There is a need for strong awareness about hyperuricaemia, especially among primary care physicians regarding when to treat and when not to treat hyperuricaemia. Further, awareness is needed on the target sUA levels to be achieved, and about all the co-morbidities that are associated with hyperuricaemia. Hyperuricaemia screening could be included in the annual general health check-up plans, as hyperuricaemia is often asymptomatic. Adherence to therapy is a challenge in hyperuricaemia management. Repeated patient counselling on the importance of treatment adherence in improving the quality of life is of utmost importance. Management of asymptomatic hyperuricaemia is challenging as it is difficult to convince asymptomatic patients to undergo routine evaluation and therapy if necessary.

Conclusion

The prevalence of hyperuricaemia is increasing, both globally and in India. The major challenge is related to initiation of therapy in asymptomatic hyperuricaemia patients. There is a need for enhanced awareness among physicians in India about the importance of lowering sUA levels and optimal management of hyperuricaemia. Physicians should be guided on carefully analysing patient condition and lifestyle before initiating ULT. Early diagnosis and streamlined management practices would aid in lowering the growing burden of hyperuricaemia in the country.

Acknowledgement

The authors thank BioQuest Solutions Pvt. Ltd. for manuscript writing and editorial assistance.

Disclosure: The expert group discussion was conducted in association with Abbott Healthcare Pvt. Ltd. This article is based on the views expressed during the expert group discussion. The views expressed and discussed in the meetings and stated in this consensus article are the independent views of the authors and not of Abbott Healthcare Pvt. Ltd.

DOI and Others

DOI: 10.7860/JCDR/2022/51970.15876

Date of Submission: Aug 17, 2021
Date of Peer Review: Oct 11, 2021
Date of Acceptance: Nov 21, 2021
Date of Publishing: Jan 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

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