Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

OBJECTIVE: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

What Is the Evidence for Treat-to-Target Serum Urate in Gout?

PURPOSE OF REVIEW: Most current clinical guidelines for gout management advocate a treat-to-target serum urate approach, although notable differences exist. Serum urate is a rational target for gout treatment given the central role of urate in disease causality, its association with key outcomes and its practicality of use in clinical practice. This review analyses the evidence for this strategy in gout. RECENT FINDINGS: Recent studies have confirmed the efficacy of urate-lowering therapy in achieving serum urate targets, both in trials using fixed doses and those applying a treat-to-target strategy. In a limited number of long-term studies (> 12-month duration), interventions that incorporate a treat-to-target serum urate approach have been shown to promote regression of tophi, reduce the frequency of gout flares and improve MRI-detected synovitis. A strong case can be made for a treat-to-target serum urate strategy in gout, supported by existing knowledge of disease pathophysiology, outcomes from urate-lowering therapy studies and emerging results of randomised strategy trials of sufficient duration.

Uptake of the Gout and Crystal Arthritis Network Consensus Statements for Gout Nomenclature.

OBJECTIVE: In 2019, the Gout and Crystal Arthritis Network (G-CAN) published consensus statements for the nomenclature of disease elements and states in gout. The aim of this study was to determine adherence to the G-CAN consensus nomenclature statements since publication. METHODS: American College of Rheumatology and EULAR conference abstracts were searched using online databases for the keywords 'gout,' 'urate,' 'uric acid,' 'hyperuricaemia,' 'tophus,' and/or 'tophi' before and after publication of the consensus statements (January 1, 2016 to December 31, 2017 and January 1, 2020 to December 31, 2021, respectively). Abstracts were manually searched for labels used to reference gout disease elements and states. Use of the G-CAN-agreed labels, as well as alternatives, were compared between the two time periods. RESULTS: There were 988 abstracts included in the analysis: 596 in 2016 to 2017 and 392 in 2020 to 2021. Use of the agreed labels 'urate' and 'gout flare' increased between the two periods. There were 219 of 383 abstracts (57.2%) with the agreed label 'urate' in 2016 to 2017 compared with 164 of 232 (70.7%) in 2020 to 2021 (P = 0.001). There were 60 of 175 abstracts (34.3%) with the agreed label 'gout flare' in 2016 to 2017 compared with 57 of 109 (52.3%) in 2020 to 2021 (P = 0.003). Consistent with the G-CAN statement, use of the label 'chronic gout' reduced between the two time periods. There were 29 of 596 abstracts (4.9%) in 2016 to 2017 that used the label 'chronic gout' compared with 8 of 392 abstracts (2.0%) in 2020 to 2021 (P = 0.02). CONCLUSION: Use of G-CAN-agreed gout labels has increased, but gout nomenclature remains imprecise. Additional efforts are needed to ensure consistent use of agreed nomenclature for gout in the scientific literature.

Comparative Risk of Gout Flares When Initiating or Escalating Various Urate-Lowering Therapy: A Systematic Review With Network Meta-Analysis.

OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis. METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively. CONCLUSION: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.

Intensive Serum Urate Lowering With Oral Urate-Lowering Therapy for Erosive Gout: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout. METHODS: We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points. RESULTS: Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups. CONCLUSION: Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout.

Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing.

AIM: Discrepancies exist between international treatment guidelines and current Australian Pharmaceutical Benefits Scheme (PBS) criteria for funding biologic disease-modifying antirheumatic drug (bDMARD) prescribing in psoriatic arthritis (PsA). We aimed to determine the prevalence of minimal disease activity (MDA) achievement and differences in inflammatory marker levels between PsA patients who have and have not met the Australian PBS criteria for bDMARDs. METHOD: Consecutive participants diagnosed with PsA were assessed for MDA components and serum inflammatory markers. For those on bDMARDs, joint counts and inflammatory markers at the time of bDMARD qualification were compared with matched rheumatoid arthritis (RA) controls. RESULTS: Minimal disease activity was achieved by 56/105 participants overall. There were no differences in inflammatory marker levels or involved joint count patterns between the PsA and RA groups at the time of bDMARD qualification. Seventy-three percent of the 53 PsA patients on bDMARD achieved MDA, vs 33% in the non-bDMARD group (P < 0.001). More bDMARD than non-bDMARD patients achieved four out of seven MDA components. Of those with any enthesitis, its prevalence was higher in the non-bDMARD group (22 vs 10, P = 0.009). Regardless of treatment, there was no difference in inflammatory marker levels between those who did and did not achieve MDA. CONCLUSION: The Australian PBS criteria, funding bDMARD prescribing for PsA, select well for MDA achievers. A high prevalence of MDA non-achievement remains in patients ineligible for bDMARD funding, and enthesitis in this population is more common. Inflammatory markers were not discriminators between treatment or MDA achievement groups.

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.

The nomenclature of the basic disease elements of gout: A content analysis of contemporary medical journals.

OBJECTIVES: There is currently no standardised nomenclature for the basic disease elements of gout. This study aimed to identify these elements and examine how they are labelled in contemporary medical literature. METHODS: We analysed articles from the ten highest ranked general rheumatology journals, and five highest ranked general internal medicine journals (by Impact Factor, according to 2015 Thomson-Reuters Journal Citation Reports), published between 1 January 2012 and 31 January 2017. For each journal, articles relevant to gout and hyperuricaemia were identified by the search terms 'gout' and/or 'urate' and/or 'uric acid' using MEDLINE. Basic disease elements were identified and their labels extracted. Labels designated 'unique' used different words or phrases to describe an element. RESULTS: A total of 549 articles were analysed. Eleven basic disease elements and 343 unique labels were identified. Labelling was imprecise for most elements. 'An episode of acute inflammation triggered by the presence of pathogenic crystals' was represented by a total of 162 unique labels; 33.6% of articles referring to this element used at least four unique labels. For articles referencing 'the circulating form of the final enzymatic product generated by xanthine oxidase in purine metabolism in humans', the labels 'uric acid' and 'urate' were used with similar frequency (63.0% and 62.5%, respectively), and both labels were used in 25.9% of articles. CONCLUSION: Labelling of the basic disease elements of gout is characterised by imprecision, inaccuracy and lack of clarity. Consensus regarding the nomenclature of these elements is required.