Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial.

OBJECTIVES: To determine whether placebo is non-inferior to low-dose colchicine for reducing gout flares during the first 6 months of allopurinol using the 'start-low go-slow' dose approach. METHODS: A 12-month double-blind, placebo-controlled non-inferiority trial was undertaken. Adults with at least one gout flare in the preceding 6 months, fulfilling the American College of Rheumatology (ACR) recommendations for starting urate-lowering therapy and serum urate ≥0.36 mmol/L were recruited. Participants were randomised 1:1 to colchicine 0.5 mg daily or placebo for the first 6 months. All participants commenced allopurinol, increasing monthly to achieve target urate <0.36 mmol/L. The primary efficacy outcome was the mean number of gout flares/month between 0 and 6 months, with a prespecified non-inferiority margin of 0.12 gout flares/month. The primary safety outcome was adverse events over the first 6 months. RESULTS: Two hundred participants were randomised. The mean (95% CI) number of gout flares/month between baseline and month 6 was 0.61 (0.47 to 0.74) in the placebo group compared with 0.35 (0.22 to 0.49) in the colchicine group, mean difference 0.25 (0.07 to 0.44), non-inferiority p=0.92. There was no difference in the mean number of gout flares/month between randomised groups over the 12-month period (p=0.68). There were 11 serious adverse events in 7 participants receiving colchicine and 3 in 2 receiving placebo. CONCLUSIONS: Placebo is not non-inferior to colchicine in prevention of gout flares in the first 6 months of starting allopurinol using the 'start-low go-slow' strategy. After stopping colchicine, gout flares rise with no difference in the mean number of gout flares/month between groups over a 12-month period. TRIAL REGISTRATION NUMBER: ACTRN 12618001179224.

Giant cell arteritis: A population-based retrospective cohort study exploring incidence and clinical presentation in Canterbury, Aotearoa New Zealand.

Background/aim: To determine the epidemiology and clinical features of giant cell arteritis (GCA) in Canterbury, Aotearoa New Zealand, with a particular focus on extra-cranial large vessel disease. Methods: Patients with GCA were identified from radiology and pathology reports, outpatient letters and inpatient hospital admissions in the Canterbury New Zealand from 1 June 2011 to 31 May 2016. Data was collected retrospectively based on review of electronic medical records. Results: There were 142 cases of GCA identified. 65.5% of cases were female with a mean age of 74.2 years. The estimated population incidence for biopsy-proven GCA was 10.5 per 100,000 people over the age of 50 and incidence peaked between 80 and 84 years of age. 10/142 (7%) people were diagnosed with large vessel GCA, often presenting with non-specific symptoms and evidence of vascular insufficiency including limb claudication, vascular bruits, blood pressure and pulse discrepancy, or cerebrovascular accident. Those with limited cranial GCA were more likely to present with the cardinal clinical features of headache and jaw claudication. Patients across the two groups were treated similarly, but those with large vessel disease had greater long-term steroid burden. Rates of aortic complication were low across both groups, although available follow-up data was limited. Conclusion: This study is the first of its kind to describe the clinical characteristics of large vessel GCA in a New Zealand cohort. Despite small case numbers, two distinct subsets of disease were recognized, differentiating patients with cranial and large vessel disease. Our results suggest that utilization of an alternative diagnostic and therapeutic approach may be needed to manage patients with large vessel disease.

Allopurinol hypersensitivity: Pathogenesis and prevention.

Allopurinol, a first line urate-lowering therapy, has been associated with serious cutaneous reactions that have a high mortality. A number of risk factors for these serious adverse reactions have been identified including ethnicity, HLA-B∗5801 genotype, kidney impairment, allopurinol starting dose, and concomitant diuretic use. There is a complex interplay between these risk factors, which may (albeit rarely) lead to allopurinol-related serious adverse events. Although oxypurinol, the active metabolite of allopurinol, has been implicated, there is no defined drug concentration at which the reaction will occur. There is no specific treatment other than the cessation of allopurinol and supportive care. Whether hemodialysis, which rapidly removes oxypurinol, improves outcomes remains to be determined. Strategies to help reduce this risk are therefore important, which includes screening for HLA-B∗5801 in high-risk individuals, commencing allopurinol at low dose, and educating patients about the signs and symptoms of severe cutaneous adverse reactions, and what to do if they occur.

Relationships Between Allopurinol Dose, Oxypurinol Concentration and Urate-Lowering Response-In Search of a Minimum Effective Oxypurinol Concentration.

The aims of this study were to determine factors that predict serum urate (SU) lowering response to allopurinol and the conversion of allopurinol to oxypurinol, and to determine a minimum therapeutic oxypurinol concentration. Data from 129 participants in a 24-month open, randomized, controlled, parallel-group, comparative clinical trial were analyzed. Allopurinol dose, SU, and plasma oxypurinol concentrations were available at multiple time points. The slope for the association between allopurinol dose and SU was calculated as a measure of sensitivity to allopurinol. The slope for the association between allopurinol dose and oxypurinol was calculated as a measure of allopurinol metabolism. Receiver operating characteristic (ROC) curves were used to identify a minimum oxypurinol concentration predictive of SU < 6 mg/dL. There was a wide range of SU concentrations for each allopurinol dose. The relationship between sensitivity to allopurinol and allopurinol metabolism for each 100 mg allopurinol dose increase varied between individuals. Body mass index (P = 0.023), creatinine clearance (CrCL; P = 0.037), ABCG2 Q141K (P = 0.019), and SU (P = 0.004) were associated with sensitivity to allopurinol. The minimum oxypurinol concentration for achieving the urate target was found to be about 104 µmol/L, but predictive accuracy was poor (ROC curve area under the curve (AUC) 0.65). The minimum therapeutic oxypurinol concentration was found to increase with decreasing renal function. Although there is a positive relationship between change in oxypurinol and change in SU concentration, a minimum therapeutic oxypurinol is dependent on CrCL and cannot reliably predict SU target. Other variables, including ABCG2 Q141K genotype, impact on sensitivity to allopurinol (ACTRN12611000845932).

Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout.

OBJECTIVE: The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. METHODS: Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. RESULTS: There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (≥80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. CONCLUSION: Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.

A Pilot Randomized Controlled Double-Blind Trial of High- Versus Low-Dose Weekly Folic Acid in People With Rheumatoid Arthritis Receiving Methotrexate.

BACKGROUND/OBJECTIVE: The aim of this study was to determine whether reducing the dose of supplemental folic acid used in conjunction with methotrexate (MTX) therapy in people with active rheumatoid arthritis (RA) improved disease control and/or increased MTX-related adverse effects. METHODS: A randomized double-blind randomized controlled trial comparing 5 mg/wk and 0.8 mg/wk folic acid was undertaken. Rheumatoid arthritis patients on MTX for 3 months or more at a stable dose for 1 month or more were recruited. All participants had DAS28 of 3.2 or greater or required a change in therapy determined by the treating clinician. Disease activity, full blood count, liver function tests, red blood cell (RBC) folate, and RBC MTX polyglutamates were assessed at weeks 0, 4, 8, 16, and 24 along with reports of adverse events. RESULTS: Forty participants were recruited. The mean (SD) change in RBC folate between week 0 and 24 was +87.9 (57.4) nmol/L in the high-dose group and -113.3 (65.7) nmol/L in the low-dose group (p < 0.05). There was no significant difference in the change in DAS28 between the high- and low-dose groups at 24 weeks (-0.13 [95% confidence interval, -0.69 to 0.43] vs -0.25 [-0.87 to 0.37], respectively [p = 0.78]). There was no significant difference in MTX-related adverse effects between the 2 groups. CONCLUSIONS: A reduction in RBC folate secondary to reduction in folic acid dose was not associated with a change in RA disease activity or MTX-related adverse effects. The prevention of MTX-related adverse effects remains the primary reason for coprescribing folic acid with MTX. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR12610000739011).

Serum urate levels and therapy in adults treated with long-term dialysis: a retrospective cross-sectional study.

BACKGROUND: The management of gout in chronic kidney disease and end-stage renal disease is challenging and remains controversial. There are limited data on the use of urate-lowering therapy in people receiving dialysis. AIM: To estimate the point prevalence of gout, gout treatment and achievement of target serum urate (SU) among adults treated with long-term dialysis. METHODS: Three secular cohorts of adults receiving dialysis for at least 90 days on 1 February 2017, 1 January 2016 and 1 January 2015 were identified. Medical records were reviewed for SU concentrations. Results were compared between haemodialysis (HD) and peritoneal dialysis (PD), and participants prescribed and not prescribed urate-lowering therapy. The percentage reduction in SU 24- and 48-h post-HD was estimated based on data from a previous study. SU concentrations were then used to estimate the percentage time the SU was <0.36 mmol/L using linear interpolation. RESULTS: Of 216 dialysis patients, 61 (point prevalence 28.2%, 95% confidence interval 22.35-34.8%) had a diagnosis of gout. The mean (SD) age among those with gout was 61 years (14.4), 46 (75.4%) were men and 18 (31.1%) identified as Maori or Pacific Island. Forty-two (68.9%) were prescribed allopurinol (mean (SD) dose 116.0 ± 66.9 mg/day). 46% had a predialysis SU ≤0.36 mmol/L on less than 25% of occasions and 23% were below target on 76-100% of occasions. SU was below target 41% of time, with no statistically significant difference in those on HD or PD (P = 0.39), and those prescribed or not prescribed allopurinol (P = 0.55). CONCLUSIONS: Gout is experienced by approximately one in four adults treated with dialysis and two-thirds are prescribed allopurinol. A minority have SU at a target sufficient to prevent gout despite allopurinol and HD. A treat to target SU should be considered in those with SU above target.

How much allopurinol does it take to get to target urate? Comparison of actual dose with creatinine clearance-based dose.

OBJECTIVE: Allopurinol dosing has frequently been limited based on creatinine clearance (CrCL), resulting in failure to achieve target serum urate (SU). The aim of this analysis was to determine how many milligrams of allopurinol above the recommended CrCL-based dose (R+) are required to achieve target SU and to investigate the factors that influence R+. METHODS: We analysed data from participants in a 24-month open, randomized, controlled, parallel-group, comparative clinical trial. Data obtained during the 12-month dose escalation (DE) phase of the study (year 1 for DE/DE and year 2 for control/DE) were combined. R+ dose was defined as the number of milligrams of allopurinol above the CrCL-based dose at the final visit. RESULTS: Of the 132 participants, R+ allopurinol dose at the final visit was ≤ 100 mg/day in 38 (28.8%), 101-200 mg/day in 46 (34.8%) and > 200 mg/day in 48 participants (37.1%). There was no significant difference between the R+ groups in the number of participants achieving target SU. There was an increase in plasma oxypurinol and a larger percentage and absolute change in SU as R+ increased. Multivariate analysis revealed CrCL, weight, baseline SU and allopurinol dose, were significantly positively associated with allopurinol dose at 12 months. There were no significant differences across R+ groups in renal or liver function adverse events, although there were numerically more serious adverse events in the higher R+ groups. CONCLUSION: A wide range of R+ doses are required to achieve target SU. Four easily obtained clinical variables (baseline SU, CrCL, weight, and allopurinol dose) may be helpful to predict allopurinol dose. TRIAL REGISTRATION: ANZCTR, ACTRN12611000845932 . Registered on 10 August 2011.

Can we predict inadequate response to allopurinol dose escalation? Analysis of a randomised controlled trial.

Objectives: To determine factors that predict inadequate serum urate (SU) lowering response in a randomized controlled trial of allopurinol dose escalation (DE) in gout. Methods: Participants undergoing allopurinol DE were classified as: complete response (CR)-reached target SU at month 9 and 12 of the DE phase or if still dose escalating at month 9 reached target SU by month 12; partial response (PR)-reached target at some stage but not fulfilling criteria for CR; or inadequate response (IR)-did not reach target SU at any time. Results: IR was uncommon, occurring in 13/150 (8.7%), compared with 82 (54.7%) CR, and 55 (36.6%) PR. Mean (s.e.m.) SU was higher at the end of the 12-month DE in IR compared with both CR and PR groups; 7.6 (0.31) vs 5.01 (0.06) and 5.97 (0.17) mg/dl respectively (P < 0.001). In univariate analysis, compete responders tended to be older, be receiving less allopurinol, have longer gout duration and were more likely to be New Zealand (NZ) European ethnicity, compared with IR+PR. Using multi-variate logistic regression analysis, only longer duration of gout and NZ European ethnicity remained significant independent predictors of CR. Baseline SU ⩾ 8 mg/dl had a sensitivity of 69.2% and specificity of 85.1% in predicting IR. The odds ratio for an IR if baseline SU was ⩾8 mg/dl was 11.7 (95% CI 3.3, 41.2). Conclusion: A minority of people with gout never reach target SU when allopurinol dose is increased in a treat-to-target manner. Approximately one-third of those with SU ⩾ 8mg/dl despite allopurinol ⩾300mg/d have an IR to DE. Trial registration: Australian New Zealand Clinical Trails Registry, https://www.anzctr.org.au, ACTRN12611000845932.

The effect of kidney function on the urate lowering effect and safety of increasing allopurinol above doses based on creatinine clearance: a post hoc analysis of a randomized controlled trial.

BACKGROUND: The use of allopurinol in people with chronic kidney disease (CKD) remains one of the most controversial areas in gout management. The aim of this study was to determine the effect of baseline kidney function on safety and efficacy of allopurinol dose escalation to achieve serum urate (SU) <6 mg/dl. METHODS: We undertook a post hoc analysis of a 24-month allopurinol dose escalation treat-to-target SU randomized controlled trial, in which 183 people with gout were randomized to continue current dose allopurinol for 12 months and then enter the dose escalation phase or to begin allopurinol dose escalation immediately. Allopurinol was increased monthly until SU was <6 mg/dl. The effect of baseline kidney function on urate lowering and adverse effects was investigated. RESULTS: Irrespective of randomization, there was no difference in the percentage of those with creatinine clearance (CrCL) <30 ml/min who achieved SU <6 mg/dl at the final visit compared to those with CrCL ≥30 to <60 ml/min and those with CrCL ≥60 ml/min, with percentages of 64.3% vs. 76.4% vs. 75.0%, respectively (p = 0.65). The mean allopurinol dose at month 24 was significantly lower in those with CrCL <30 ml/min as compared to those with CrCL ≥30 to <60 ml/min or CrCL ≥60 ml/min (mean (SD) 250 (43), 365 (22), and 460 (19) mg/day, respectively (p < 0.001)). Adverse events were similar among groups. CONCLUSIONS: Allopurinol is effective at lowering urate even though and accepting that there were small numbers of participants with CrCL <30 ml/min, these data indicate that allopurinol dose escalation to target SU is safe in people with severe CKD. The dose required to achieve target urate is higher in those with better kidney function. TRIAL REGISTRATION: Australian and New Zealand Clinical trials Registry, ACTRN12611000845932 . Registered on 10 August 2011.

Management of Gout in a Hospital Setting: A Lost Opportunity.

OBJECTIVE: Management of gout is frequently suboptimal. The aim of this study was to determine the proportion of patients presenting to Christchurch Hospital for a gout flare and to determine whether management for both acute flares and urate lowering was in accordance with international recommendations. METHODS: A retrospective audit was undertaken of all admissions to Christchurch Hospital from June 1, 2013, to May 31, 2014, in which gout was coded as a primary or secondary discharge diagnosis. Information including demographics, comorbidities, concomitant medications, treatment of acute gout, and urate lowering was collected. RESULTS: A total of 235 acute admissions for gout in 216 individuals were identified. Eleven individuals had 2 admissions and 4 individuals had 3 admissions. In 95/235 admissions (40.4%), gout was the primary diagnosis. Gout accounted for 95/77,321 (0.12%) of acute admissions. The treatment of acute gout was prednisone monotherapy in 170/235 (72.3%) of admissions. Serum urate was measured at some point during 123/235 (52.3%) of admissions, with only 19/123 (15.4%) at target urate level (< 0.36 mmol/l). At 60 of the 235 admissions, urate-lowering therapy was already being prescribed. Nine out of 175 patients (5.1%) not treated with urate-lowering therapy at admission commenced allopurinol and 32/174 (18.4%) had commencement of urate-lowering therapy recommended in the discharge plan. CONCLUSION: Rates of admission for gout are similar to that observed in other studies. Failure to initiate, change, or recommend alterations in urate-lowering therapy to achieve target urate in people with gout admitted to hospital represents a significant lost opportunity to improve longterm gout management.

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study.

OBJECTIVES: To determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout. METHODS: People, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24. RESULTS: The mean (SE) change in SU from month 12 to 24 was -1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups. CONCLUSIONS: The majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment. TRIAL REGISTRATION NUMBER: ACTRN12611000845932.

A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

OBJECTIVES: To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. METHODS: A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs). RESULTS: 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups. CONCLUSIONS: Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated. TRIAL REGISTRATION NUMBER: ANZCTR12611000845932; Results.

A population pharmacokinetic model to predict oxypurinol exposure in patients on haemodialysis.

PURPOSE: The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. METHODS: Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not receiving dialysis were used to develop a population pharmacokinetic model in NONMEM. Deterministic simulations were used to predict the steady-state area under the oxypurinol plasma concentration time curve over 1 week (AUC7days). RESULTS: The pharmacokinetics of oxypurinol were best described by a one-compartment model with a separate parameter for dialytic clearance. Allopurinol 100 mg daily produced an AUC7days of 279 µmol/L h in dialysis patients, a value 50-75 % lower than the AUC7days predicted for patients with normal renal function taking 200 to 400 mg daily (427-855 µmol/L h). Dosing pre-dialysis resulted in about a 25-35 % reduction in exposure compared to post-dialysis. CONCLUSIONS: Oxypurinol is efficiently removed by dialysis. The population dialytic and total (non-dialytic) clearance of oxypurinol were found to be 8.23 and 1.23 L/h, standardised to a fat-free mass of 70 kg and creatinine clearance of 6 L/h, respectively. Our results suggest that if the combination of low-dose allopurinol and haemodialysis does not result in sustained urate lowering below treatment targets (serum urate ≤0.36 mmol/L), then allopurinol doses may be increased to optimise oxypurinol exposure.

Allopurinol and kidney function: An update.

Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.

Association between environmental exposures and granulomatosis with polyangiitis in Canterbury, New Zealand.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis. While aetiology is unknown the prominent respiratory involvement suggests inhaled antigens may be involved. The aim of this study was to identify environmental risk factors associated with GPA in Canterbury, New Zealand. METHODS: A case-controlled study was undertaken. All GPA cases fulfilled American College of Rheumatology (ACR), Chapel Hill Consensus Criteria (CHCC) or the European Medicines Agency (EMA) criteria. Each case was gender matched with four controls - 2 musculoskeletal (osteoarthritis or fracture) and 2 respiratory (asthma or chronic obstructive pulmonary disease). One musculoskeletal control and one respiratory control were age matched with the case at the time of the interview (interview) and the remaining two controls were age matched at the time their case experienced the first symptom of vasculitis (index). A structured questionnaire to assess potential environmental agents was administered without blinding for case/control status. Data were analyzed using conditional logistic regression to allow for the individual matching of cases and controls to assess for association between environmental factors and GPA. RESULTS: 49 cases and 196 controls were recruited. 53 % were male and the mean ± standard deviation (SD) age of the cases was 64.9 ± 12.4 years, interview controls 65.1 ± 12.4.years and index controls 53.9 ± 14.5 years. Any reported exposure to dust (specifically silica and grain dust) was associated with GPA, odds ratio (OR) 3.6 (95 % confidence interval (CI); 1.5-8.3, p = 0.003). Occupation as a farm worker was associated with GPA OR 3.43 (1.5-7.5, p = 0.002). Specific gardening activities were associated with GPA including digging (OR 3.2; 1.4-7.0; p = 0.003), mowing (OR 2.7; 1.3-5.8; p = 0.008) and planting (OR 2.6; 1.2-5.5; p = 0.013). CONCLUSION: We have replicated findings from northern hemisphere studies identifying dust exposure as well as farm exposure as risk factors for the development of GPA. We have shown activities associated with exposure to inhaled antigens, in particular those related to farming or gardening activities may increase the risk of GPA.

Patient Information about Gout: An International Review of Existing Educational Resources.

OBJECTIVE: Inadequate patient information about gout may contribute to poor disease outcomes. We reviewed existing educational resources for gout to identify strengths and weaknesses and compare resources cross-nationally. METHODS: Content, readability, and dietary recommendations were reviewed using a sample of 30 resources (print and Web-based) from 6 countries. RESULTS: More than half of the resources were written at a highly complex level. Some content areas were lacking coverage, including comorbidity risks, uric acid target levels, and continuing allopurinol during acute attacks. CONCLUSION: Our findings suggest significant room for improvement in gout patient educational resources, particularly regarding self-management.

Urate-lowering therapy: current options and future prospects for elderly patients with gout.

Gout is increasingly seen in the elderly population, in large part due to physiological decline in renal function with age, and as a result of therapy for comorbidities, in particular the use of diuretic therapies for hypertension and congestive heart failure. Urate-lowering therapy (ULT) is the cornerstone of successful long-term gout management with the aim of achieving a sustained reduction in urate (<0.36 mmol/L, or lower [<0.30 mmol/L] in those with tophi). After decades during which there has been relatively little interest in developing new agents to treat gout, the last 5-10 years has seen a plethora of new agents with several now used in routine clinical practice. There has also been a renewed focus on the optimal use of established ULT, specifically allopurinol, which remains the first-line therapy for most patients. There is emerging data on its use in patients with renal impairment and better recognition of risk factors of the rare but potentially lethal allopurinol hypersensitivity syndrome (AHS). Febuxostat, a new xanthine oxidase inhibitor, is now established in everyday practice. Uricosuric agents may be indicated in certain patient groups, whilst a new class of recombinant uricases (pegloticase) given by intravenous infusion may achieve dramatic and rapid urate-lowering effects. Cost and other factors have thus far limited its use to the very severe cases. Furthermore, increased understanding of urate metabolism has led to the development of a number of drugs currently under clinical evaluation. Common therapeutic targets are the urate transporters in the kidney and alternative xanthine oxidase inhibition pathways. These advances bode well for the better management of gout and hyperuricaemia in our elderly patients.

Comparison of two plasma urate assays in patients receiving vitamin C supplementation.

The aim of this study was to compare plasma urate (PU) concentrations using two different assays in patients receiving vitamin C supplementation. PU was measured using two routinely available enzymatic uricase methods: (1) uric acid plus method (ascorbate oxidase assay), and (2) uric acid method (non-ascorbate oxidase assay). Twenty patients receiving allopurinol were randomised to an increase in allopurinol dose or commence vitamin C 500  mg/d on a 1:1 ratio. Twenty patients not receiving allopurinol were randomised to start allopurinol or vitamin C 500  mg/d on a 1:1 ratio. Trough fasting samples for plasma ascorbate and urate were measured weekly until week 8. There was no significant difference in the mean PU measured by the two assays. In patients not receiving supplemental vitamin C the mean PU concentrations were identical for both assays. For patients receiving supplemental vitamin C the mean PU concentrations for the ascorbate oxidase assay was 0.525  mmol/L (SE 0.034) and for the non-ascorbate oxidase assay 0.510  mmol/L (SE 0.033), p = 0.079.There is a small non-significant difference in measured PU in patients receiving supplemental vitamin C between the two assays. The assay which does not include ascorbate oxidase results in consistently lower PU concentrations compared to the assay which includes ascorbate oxidase.

Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial.

OBJECTIVE: Studies in human volunteers have shown that vitamin C reduces serum urate (SU) levels. The aim of this study was to determine the effects of vitamin C on SU levels in patients with gout. METHODS: Patients with gout and an SU level >0.36 mmoles/liter (6 mg/dl) were recruited. Twenty patients already taking allopurinol were randomized to receive an increase in the dose of allopurinol or to commence taking vitamin C (500 mg/day). Twenty patients who had not been taking allopurinol were randomized to start receiving either allopurinol (up to 100 mg/day) or vitamin C (500 mg/day). Levels of plasma ascorbate, creatinine, and SU were measured on day 0 and week 8. RESULTS: There was no significant difference in the baseline SU level or estimated glomerular filtration rate (eGFR) between those who received vitamin C and those who did not (for SU, mean ± SEM 0.50 ± 0.11 mmoles/liter [8.4 ± 1.8 mg/dl] versus 0.50 ± 0.09 mmoles/liter [8.4 ± 1.5 mg/dl]; for eGFR, mean ± SEM 65.5 ± 3.5 ml/minute/1.73 m(2) versus 67.9 ± 4.6 ml/minute/1.73 m(2) ). Among the randomized patients, 30% in the vitamin C group and 25% in the no vitamin C control group were receiving diuretics. In the patients receiving vitamin C, there was a significant increase between day 0 and week 8 in the plasma ascorbate level. The reduction in SU level over 8 weeks was significantly less in those patients receiving vitamin C compared to those who started or increased the dose of allopurinol (mean reduction 0.014 mmoles/liter [0.23 mg/dl] versus 0.118 mmoles/liter [1.9 mg/dl]; P < 0.001). CONCLUSION: A modest dosage of vitamin C (500 mg/day) for 8 weeks had no clinically significant urate-lowering effects in patients with gout, despite the fact that plasma ascorbate levels increased. These results differ from previous findings in healthy control subjects with hyperuricemia. The uricosuric effect of modest-dose vitamin C appears to be small in patients with gout, when administered as monotherapy or in combination with allopurinol.