Relationship between serum urate and changes in dual-energy CT monosodium urate crystal volume over 1 year in people with gout: an individual participant data analysis.

Objectives: The dynamics of monosodium urate (MSU) crystal changes across a range of serum urate concentrations in people with gout are unknown. This study aimed to systematically examine the relationship between serum urate and changes in dual-energy CT (DECT) urate volume in people with gout and stable serum urate concentrations.

Methods: Individual participant data were analysed from three studies of people with gout.

Analysis of Gout Remission Definitions in a Randomized Controlled Trial of Colchicine Prophylaxis for People With Gout Initiating Allopurinol.

Objective: To investigate (1) the effect of colchicine prophylaxis on gout remission when commencing urate-lowering therapy (ULT), and (2) illness perceptions of people in remission using 2 definitions of gout remission.

Methods: Data from a 12-month double-blind placebo-controlled trial of 200 people with gout commencing allopurinol were analyzed. Participants were randomly assigned to prophylaxis with 0.

Predicting Gout Flares in People Starting Allopurinol Using the Start-Low Go-Slow Dose Escalation Strategy.

Objective: The study objective was to determine predictors of gout flare when commencing allopurinol using the "start-low go-slow" dose escalation strategy.

Methods: A post hoc analysis of a 12-month double-blind placebo-controlled noninferiority trial with participants randomized 1:1 to colchicine 0.5 mg daily or placebo for the first six months was undertaken.

The development and evaluation of dose-prediction tools for allopurinol therapy (Easy-Allo tools).

Aims: Dose escalation at the initiation of allopurinol therapy can be protracted and resource intensive. Tools to predict the allopurinol doses required to achieve target serum urate concentrations would facilitate the implementation of more efficient dose-escalation strategies. The aim of this research was to develop and externally evaluate allopurinol dosing tools, one for use when the pre-urate-lowering therapy serum urate is known (Easy-Allo1) and one for when it is not known (Easy-Allo2).

The Tophus Impact Questionnaire (TIQ-20): responsiveness to change during urate-lowering therapy.

Objectives: In 2015, the 20-item Tophus Impact Questionnaire (TIQ-20) was developed as a tophus-specific patient-reported outcome measure. The aim of this study was to determine whether TIQ-20 scores change during urate-lowering therapy.

Methods: We analysed data from a 2-year clinical trial of allopurinol dose escalation using a treat-to-target serum urate approach.

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.

Changes in Tophus Composition During Urate-Lowering Therapy: A Dual-Energy Computed Tomography Study.

Objective: The gouty tophus is an organized structure composed of monosodium urate (MSU) crystals and chronic inflammatory soft tissue. This dual-energy computed tomography (DECT) study aimed to determine whether the composition of the tophus changes during urate-lowering therapy.

Methods: Serial DECT scans from 32 people with gout were obtained over 2 years of allopurinol therapy, dose-escalated to serum urate of <0.

Long-Term Follow-up of a Randomized Controlled Trial of Allopurinol Dose Escalation to Achieve Target Serum Urate in People With Gout.

Objective: To determine the long-term use of and adherence to urate-lowering therapy (ULT), serum urate (SU) control, and self-reported flares in participants from a randomized controlled trial of allopurinol dose escalation, in order to achieve target SU concentration (< 0.36 mmol/L) in people with gout.

Methods: For surviving study participants, ULT dispensing and SU testing within the preceding 12 months was obtained by medical record review.

Effect of omega-three supplementation on serum urate and gout flares in people with gout; a pilot randomized trial.

Objectives: To determine the effect of omega-three supplementation with fish oil on serum urate, weight and body mass index (BMI) in people with gout.

Methods: A pilot 6-month, randomized, open-label clinical trial was undertaken in people with gout with serum urate ≥ 0.36 mmol/l.

Lack of effect of tart cherry concentrate dose on serum urate in people with gout.

Objectives: Cherry concentrate has been suggested to reduce serum urate (SU) and gout flares. The aims of this study were to determine the magnitude of the effect of tart cherry concentrate on SU in people with gout, the most effective dose of tart cherry concentrate for lowering SU, and adverse effects.

Methods: Fifty people with gout and SU > 0.

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.

Associations of Gout and Baseline Serum Urate Level With Cardiovascular Outcomes: Analysis of the Coronary Disease Cohort Study.

Objective: To determine whether gout and serum urate (SU) levels are associated with increased risk of death, time to first readmission for any cardiovascular event, or incident heart failure in individuals with cardiovascular disease.

Methods: Individuals presenting with an acute coronary syndrome (ACS) were enrolled in the Coronary Disease Cohort Study. Clinical data were collected from the medical records at the index hospital admission, and clinical, echocardiographic, and biochemical data were collected postdischarge.

Effects of Allopurinol Dose Escalation on Bone Erosion and Urate Volume in Gout: A Dual-Energy Computed Tomography Imaging Study Within a Randomized, Controlled Trial.

Objective: To examine whether allopurinol dose escalation to achieve serum urate (SU) target can influence bone erosion or monosodium urate (MSU) crystal deposition, as measured by dual-energy computed tomography (DECT) in patients with gout.

Methods: We conducted an imaging study of a 2-year randomized clinical trial that compared immediate allopurinol dose escalation to SU target with conventional dosing for 1 year followed by dose escalation to target, in gout patients who were receiving allopurinol and who had an SU level of ≥0.36 mmoles/liter.

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.

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.

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.

The impact of diuretic use and ABCG2 genotype on the predictive performance of a published allopurinol dosing tool.

Aim: This research aims to evaluate the predictive performance of a published allopurinol dosing tool.

Methods: Allopurinol dose predictions were compared to the actual dose required to achieve serum urate (SU) <0.36 mmol l using mean prediction error.

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.

Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A Laboratory and Clinical Study.

Introduction: Numerous observational studies have reported that serum urate concentration positively correlates with bone density and reduced risk of fractures. The aim of this study was to examine whether soluble urate directly influences bone remodelling.

Methods: In laboratory studies, the in vitro effects of soluble urate were examined in osteoclast, osteoblast and osteocyte assays at a range of urate concentrations consistent with those typically observed in humans (up to 0.

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).

Fructose malabsorption in people with and without gout: A case-control study.

Background: Higher fructose intake has been associated with hyperuricaemia and gout. Some individuals malabsorb fructose in the small intestine. The aims of this study were to determine the rate of fructose malabsorption and the effects of gout and fructose malabsorption on serum urate in people with and without gout.

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.

Assessment of the relationship between methotrexate polyglutamates in red blood cells and clinical response in patients commencing methotrexate for rheumatoid arthritis.

Background And Objectives: Therapeutic drug monitoring in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX, MTXGlu1) has not been established. In this study, we aim to explore the relationship between red blood cell (RBC) concentrations of MTX and its polyglutamate metabolites (MTXGlu(n); n = 2, 3, 4, 5) and clinical response in RA patients commencing MTX.

Methods: The binding activity of MTXGlu(n) to three putative enzymes involved in the MTX mechanism of action—dihydrofolate reductase, thymidylate synthase, and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase—was simulated.

Development of a patient-reported outcome measure of tophus burden: the Tophus Impact Questionnaire (TIQ-20).

Background: Tophus burden is currently measured using physical examination and imaging methods. The aim of this study was to develop a patient-reported outcome (PRO) tool to assess tophus burden in people with gout.

Methods: The responses from interviews with 25 people with tophaceous gout were used to generate items for a preliminary PRO tool.

Myeloperoxidase and oxidation of uric acid in gout: implications for the clinical consequences of hyperuricaemia.

Objectives: The aims of this study were to establish whether, in patients with gout, MPO is released from neutrophils and urate is oxidized to allantoin and if these effects are attenuated by allopurinol.

Methods: MPO, urate, allantoin and oxypurinol were measured in plasma from 54 patients with gout and 27 healthy controls. Twenty-three patients had acute gout, 13 of whom were receiving allopurinol, and 31 had intercritical gout, 20 of whom were receiving allopurinol.