Metabolic
How NZ, Australian, and ACR/EULAR guidelines differ on when to start urate-lowering therapy, how aggressively to titrate, and what happens when allopurinol fails - with a close look at what gout management looks like in NZ given the highest prevalence rates in the developed world.
Scope: gout in adults managed in primary care, including acute flare treatment and long-term urate-lowering therapy. Pseudogout (CPPD) is not covered.
Where they agree
Where they diverge
Comparison
| Domain | NZ - BPAC 2022 | AU - RACGP | International - ACR 2020 / EULAR 2016 |
|---|---|---|---|
| Diagnosis | Clinical diagnosis is acceptable in a classic presentation: podagra, rapid-onset monoarthritis, hyperuricaemia, and response to colchicine. Synovial fluid analysis with monosodium urate (MSU) crystal identification is the gold standard and should be sought where possible to confirm the diagnosis, particularly at first presentation or if atypical features are present. | Aligned approach. RACGP acknowledges clinical diagnosis in typical presentations but emphasises that confirmation by joint aspiration and MSU crystal identification avoids misdiagnosis (septic arthritis, pseudogout, reactive arthritis). Dual-energy CT (DECT) is increasingly available in AU specialist settings as a non-invasive alternative. | ACR/EULAR: MSU crystal identification in synovial fluid or tophus is definitive. The ACR/EULAR classification criteria (2015) are primarily for research; in clinical practice, a diagnostic algorithm using serum urate, joint characteristics, and imaging features supports diagnosis when aspiration is not possible. Ultrasound (double-contour sign) and DECT have high specificity for gout. |
| Acute flare treatment |
Three equally effective first-line options - choose based on patient factors: Colchicine 0.5 mg twice or three times daily for 3-5 days. Reduce dose in eGFR <30.Funded NSAIDs (e.g. indomethacin, naproxen) at anti-inflammatory doses for 3-5 days. Avoid in CKD, peptic ulcer disease, anticoagulation.Funded Prednisolone 30-40 mg daily for 3-5 days (taper over 1-2 weeks). Use when colchicine and NSAIDs are both contraindicated.Funded High-dose colchicine (1 mg loading, then 0.5 mg hourly) is no longer recommended - equivalent efficacy to low-dose with significantly higher GI toxicity. |
Same three-option approach. RACGP also notes intra-articular corticosteroid injection as effective for monoarthritis where aspiration has been performed. Recommends starting treatment within hours of flare onset for best effect. Combination therapy (colchicine plus NSAID) is not routinely recommended but may be used for severe or polyarticular flares. |
ACR 2020 strongly recommends all three options; choice guided by comorbidities and patient preference. Low-dose colchicine (0.5 mg twice daily) is preferred over high-dose for its equivalent efficacy and lower toxicity.1 Conditionally recommends IL-1 inhibitors (anakinra, canakinumab) for refractory or contraindicated cases where colchicine, NSAIDs, and corticosteroids cannot be used. Not funded in NZ for this indication.IL-1 inhibitors not funded NZ |
| When to start ULT |
BPAC 2022 recommends ULT for: ≥2 flares per year Tophi present Urate nephropathy or urolithiasis CKD ≥3 After a first uncomplicated flare, ULT is not routinely recommended in BPAC guidance; lifestyle advice and flare management are prioritised. This is more conservative than ACR 2020 for high-risk first presentations. |
Broadly aligned with BPAC for recurrent/complicated disease. RACGP acknowledges the emerging evidence for earlier ULT initiation and notes that a first flare with high serum urate (>535 µmol/L) or CKD may warrant ULT discussion. Shared decision-making is emphasised. |
ACR 2020: strongly recommends ULT for: ≥2 flares/year, any tophi, urate nephropathy, urolithiasis, or CKD stage ≥3. Conditionally recommends ULT after the first gout flare if any of the following: CKD ≥3, serum urate ≥535 µmol/L (9 mg/dL), or urolithiasis.2 EULAR 2016: generally recommends ULT from the second attack, but earlier in severe hyperuricaemia (>535 µmol/L), CKD, tophi, or joint damage. Rationale: earlier ULT initiation reduces cumulative urate crystal burden, joint damage, and long-term flare frequency. |
| Serum urate target (treat-to-target) |
Target: <0.36 mmol/L (6 mg/dL) for all patients on ULT. Target: <0.30 mmol/L (5 mg/dL) for tophaceous or severe gout (to accelerate crystal dissolution). Check serum urate 4-6 weeks after any dose change, then 3-monthly until target is stable, then 6-monthly. Many patients are undertreated because serum urate is not monitored systematically after allopurinol is started. |
Identical targets. RACGP emphasises treat-to-target as a formal strategy: titrate ULT and monitor serum urate at each review, not just at initiation. Reminds clinicians that the presence of tophi indicates a large urate crystal burden requiring sustained time below target before tophi resolve. | ACR 2020 and EULAR 2016 use identical targets: <0.36 mmol/L for most, <0.30 mmol/L for severe/tophaceous disease. ACR 2020 strongly recommends against targeting serum urate below 0.18 mmol/L (3 mg/dL) indefinitely, as very low urate may have adverse neurological effects in older adults. Treat-to-target with monitoring is the cornerstone of effective gout management - hyperuricaemia without a serum urate target is undertreated gout. |
| Allopurinol dosing and titration |
Start at 100 mg/day (or 50 mg/day in CKD stage ≥3).Funded Titrate by 100 mg every 4 weeks, checking serum urate at each step. There is no fixed ceiling at 300 mg: most patients require 400-600 mg/day to reach target, and doses up to 800-900 mg/day are used in severe disease. The common practice of stopping at 300 mg regardless of serum urate is a major cause of treatment failure. In CKD, the starting dose is lower but titration continues - renal impairment does not preclude reaching an effective dose; it just requires more cautious up-titration. |
Same approach. RACGP explicitly states the 300 mg ceiling is a myth and that dose titration to serum urate target should continue beyond this point. Allopurinol is listed as PBS-funded with no restrictions. In practice, slower titration is used in older adults and those with CKD.PBS | ACR 2020: start allopurinol at ≤100 mg/day (≤50 mg/day in CKD ≥3); titrate every 2-4 weeks until serum urate target is achieved. No maximum dose specified in the guideline - the dose ceiling in the product information is not a clinical ceiling. EULAR 2016 recommends starting at 100 mg/day and increasing by 100 mg every 2-4 weeks. Both guidelines emphasise that starting doses well below target doses and slow titration significantly reduces the risk of allopurinol hypersensitivity syndrome.3 |
| Febuxostat and second-line ULT |
Febuxostat is not funded in NZ.Not funded When allopurinol is not tolerated or fails to achieve the serum urate target at maximum dose, the funded alternatives are: Probenecid: funded, uricosuric agent. Less effective than febuxostat and loses efficacy as eGFR falls below 30-45 mL/min/1.73m² - the very patients who need alternative ULT most often cannot use it.Funded Allopurinol desensitisation protocols exist for mild hypersensitivity reactions and may be attempted at specialist level. For severe allopurinol hypersensitivity (DRESS, SJS), desensitisation is contraindicated. For patients who genuinely cannot use allopurinol and for whom probenecid is unsuitable: refer to rheumatology and discuss unfunded febuxostat at patient expense. |
Febuxostat is PBS-listed as second-line ULT for patients with contraindications to, or intolerance of, allopurinol.PBS Probenecid is also available. RACGP notes that febuxostat should be used with caution in patients with established CVD, reflecting the CARES trial data showing a higher rate of cardiovascular death with febuxostat versus allopurinol (though all-cause mortality was similar). |
ACR 2020: conditionally recommends febuxostat as second-line if allopurinol is not tolerated or target urate is not achieved at maximum dose. Recommends against febuxostat in patients with a history of MI or stroke (CARES trial cardiovascular signal).4 EULAR 2016: febuxostat is the preferred second-line option if allopurinol fails or is contraindicated, with the cardiovascular caution noted. Pegloticase (IV recombinant uricase) for refractory tophaceous gout. The gap between international recommendations and NZ funded options is most acute here: a patient with CKD who fails allopurinol and cannot use probenecid has no funded alternative in NZ. |
| Flare prophylaxis during ULT initiation |
Low-dose colchicine 0.5 mg daily (or twice daily where tolerated and renal function allows) during the first 3-6 months of ULT.Funded Starting ULT frequently triggers a flare due to crystal mobilisation; prophylaxis reduces this substantially. Do not delay ULT initiation for this reason. If a flare occurs during ULT, continue ULT and treat the flare - stopping ULT prolongs the course. Reduce colchicine dose in eGFR <30; avoid in severe renal impairment. NSAIDs are an alternative prophylaxis if colchicine is not tolerated. |
Identical approach. RACGP recommends continuing prophylaxis for at least 6 months, or longer if tophi are present (tophi may not resolve for 12-24 months of effective ULT). Notes that the purpose of prophylaxis is not to treat the underlying disease but to bridge the patient through the period of crystal mobilisation. | ACR 2020 strongly recommends prophylaxis for at least 3-6 months, and for a minimum of 6 months after achieving serum urate target. If tophi are present, continue prophylaxis until tophi resolve. Low-dose colchicine is preferred; low-dose NSAIDs are an alternative. IL-1 inhibitors for patients who cannot use either. Do not start ULT during an acute flare unless ULT was already established before the flare began. |
| HLA-B*5801 screening |
HLA-B*5801 is strongly associated with severe allopurinol hypersensitivity reactions (DRESS, SJS/TEN) and is present at significantly higher frequency in Han Chinese, Korean, Thai, and some Polynesian populations compared with Europeans. BPAC 2022 and NZ rheumatology groups recommend considering HLA-B*5801 testing before initiating allopurinol in patients of Southeast Asian, East Asian, or Polynesian ancestry. Testing is available through genetic laboratories in NZ but is not universally performed in primary care.Consider in high-risk ancestry A positive result does not absolutely preclude allopurinol use, but the risk of severe cutaneous adverse reactions is high enough that alternatives should be strongly considered. |
RACGP recommends HLA-B*5801 testing in patients of Han Chinese, Korean, Thai, and other Southeast Asian descent before starting allopurinol. Testing is Medicare-rebateable in AU for this indication. The frequency of the allele in Aboriginal and Torres Strait Islander populations is also elevated relative to Europeans.Medicare rebateable | ACR 2020: conditionally recommends HLA-B*5801 screening before allopurinol in patients of Southeast Asian descent (Han Chinese, Korean, Thai) and in African Americans (elevated allele frequency). EULAR 2016 also recommends testing in relevant populations.5 If HLA-B*5801 positive, febuxostat is the preferred ULT; if febuxostat unavailable, proceed with extreme caution or consider allopurinol desensitisation at specialist level. |
| Lifestyle and comorbidities | Reduce alcohol (beer and spirits are higher-risk than wine; no safe level for gout control). Reduce purine-rich foods (red meat, organ meats, shellfish, sardines). Reduce fructose-containing beverages (soft drinks, fruit juice). Increase hydration. Weight loss if indicated. Review medications that raise serum urate: thiazide diuretics, low-dose aspirin, ciclosporin. Consider switching thiazide to an alternative antihypertensive if gout is difficult to control. Losartan has mild uricosuric properties and may be preferred in T2D with hypertension and gout. |
Identical lifestyle advice. RACGP notes that lifestyle modification alone rarely achieves a serum urate target in established gout and should be seen as adjunctive to ULT rather than an alternative. Addresses medication review including the loop diuretic consideration. | ACR 2020 and EULAR 2016 recommend lifestyle modification for all patients but acknowledge it is insufficient as sole treatment for established gout. Both note the urate-lowering effect of cherry extract or cherry juice (modest, evidence limited) but do not formally recommend it. ACR 2020 conditionally recommends against routine vitamin C supplementation as a urate-lowering strategy. |
| Refractory tophaceous gout |
For patients with tophaceous gout who fail oral ULT: review adherence and dose optimisation first. If genuinely refractory, refer to rheumatology. Pegloticase (IV recombinant uricase, Krystexxa): not funded in NZ and not routinely available. Some patients access it privately at significant cost.Not funded Surgical debridement of tophi is occasionally required for mechanical compromise (nerve compression, ulceration, joint destruction). |
Referral to rheumatology for refractory tophaceous disease. Pegloticase is not currently PBS-listed in AU but is used in specialist centres via special access scheme. Intravenous uricase achieves rapid urate reduction and tophus dissolution in patients who cannot tolerate or respond to oral ULT.Special access AU | ACR 2020 conditionally recommends pegloticase for patients with severe gout burden (tophi, frequent flares, joint damage) who have not responded to or cannot tolerate oral ULT at appropriate doses. Pegloticase produces dramatic serum urate reduction; immunogenicity can limit its effect. Co-administration with immunosuppression (mycophenolate, methotrexate) to reduce antibody formation is under study. EULAR similarly endorses pegloticase for severe refractory cases. |
NZ clinical context
PHARMAC funding, NZ gout epidemiology, and population-specific considerations
The NZ funded pharmacotherapy toolkit for gout is straightforward but has one significant gap at the second-line ULT level:
Gout is one of the most undertreated conditions in general practice, and the single most correctable reason is the widespread belief that 300 mg is the maximum allopurinol dose. It is not. The 300 mg dose appears in product information as a standard adult starting reference point, not a ceiling. Most patients require 400-600 mg/day to achieve a serum urate below 0.36 mmol/L; some with heavy urate burden need 800-900 mg. Titrating to 300 mg and then checking a box is treating the prescription, not the disease. Check the serum urate 4-6 weeks after each dose increase. If it is above 0.36 mmol/L, the dose is not high enough.
NZ Maori and Pacific peoples have gout prevalence rates of 6-10%, and in some Pacific communities approaching 15%, making NZ one of the highest-burden countries for gout globally.6 The mechanisms are primarily genetic: loss-of-function variants in the SLC22A12 gene (encoding the renal urate transporter URAT1) are common in Polynesian populations and severely impair renal uric acid excretion regardless of diet or alcohol intake.7 This is not a lifestyle problem alone; it is a transportopathy. Dietary advice without effective ULT is insufficient management in this group.
Clinically, this means:
If a patient reaches the maximum tolerated allopurinol dose (or has a contraindication to it) and serum urate remains above target:
Bottom line for NZ practice
What this means in the consulting room
Sources