Outcome Measures for Gout Clinical Trials: a Summary of Progress

Lautour, Hugh de; Dalbeth, Nicola; Taylor, William J.

doi:10.1007/s40674-015-0014-7

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…All other outcomes were specified as important. Without standardized definitions for gout flare as an outcome , flare definitions varied by duration of follow‐up in the various studies. Based on Patient Panel input, we specified that longer‐term outcomes (e.g., 24 months) would be critical, while shorter durations (e.g., <12 months) were considered important; it was recognized that very short time points (e.g., <6 months) may reflect the expected flares during ULT initiation.…”

Section: Methodsmentioning

confidence: 99%

2020 American College of Rheumatology Guideline for the Management of Gout

Fitzgerald

Dalbeth

Mikuls

et al. 2020

Arthritis Care & Research

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558

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Objective To provide guidance for the management of gout, including indications for and optimal use of urate‐lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. Methods Fifty‐seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta‐analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. Results Forty‐two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first‐line ULT, including for those with moderate‐to‐severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat‐to‐target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. Conclusion Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

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Section: Methodsmentioning

confidence: 99%

2020 American College of Rheumatology Guideline for the Management of Gout

Fitzgerald

Dalbeth

Mikuls

et al. 2020

Arthritis Care & Research

Self Cite

606

558

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“…[148, [164][165][166] DAMPs damage-associated molecular patterns, HMGB1 high-mobility group box 1 protein, HSP heat shock protein, mtDNA mitochondrial DNA, MSU monosodium urate caspase-1 [126,127]. The injection of ASC specks into mice is also sufficient to generate inflammatory responses.…”

Section: S100a9mentioning

confidence: 99%

“…Like cholesterol crystals, MSU crystals are phagocytosed by macrophages to induce lysosomal rupture and subsequent NLRP3 inflammasome activity [165]. Mouse models suggested that targeting NLRP3 and IL-1 would be beneficial in the treatment of gout, with subsequent clinical trials using anti-IL-1 biologics proving this to be correct [166]. Therefore, there is significant evidence implicating mammalian particulate DAMPs as inducers of IL-1-driven disease.…”

Section: Cholesterol Crystals and Msumentioning

confidence: 99%

Pyroptosis versus necroptosis: similarities, differences, and crosstalk

2018

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“…In one retrospective chart review, disease control for patients with gout was defined as a 12‐month average serum urate level less than or equal to 6 mg/dl, no flares, and no tophi (three of the five criteria in the proposed remission criteria), and it was noted that only 11% of 858 patients whose records were evaluated achieved this goal (). The Outcome Measures in Rheumatology Clinical Trials (OMERACT) also endorsed specific domains that should be assessed in clinical trials of therapies for chronic gout and corresponding instruments for their measurement (). Based on OMERACT core domains and Delphi exercises, the GAS was developed.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Proposed Criteria for Remission and Evidence‐Based Development of Criteria for Complete Response in Patients With Chronic Refractory Gout

Schlesinger

Edwards

Khanna

et al. 2019

ACR Open Rheumatology

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Objective. The objective of this study is to assess criteria for gout remission and to use the results to inform criteria for a complete response (CR).Methods. A post hoc analysis of two clinical trials was undertaken to determine the frequency with which subjects with chronic refractory gout who were treated with pegloticase met remission criteria. Mixed modeling was then employed to identify the components that best correlated with time to maximum benefit.Results. Of the 56 subjects treated with biweekly pegloticase for whom adequate data were collected, 48.2% met the remission criteria. When subjects with persistent lowering of urate levels were examined separately, 27 of 32 (84.4%) met the criteria for remission. In contrast, even when the requirement for lowering of serum urate levels was waived, only 2 of 24 (8.3%) subjects without persistent lowering of urate levels and 0 of 43 subjects receiving placebo met criteria. Mixed modeling indicated that in addition to urate levels, assessment of tophi, swollen joints, and tender joints and patient global assessment best correlated with time to maximum benefit. Using these criteria of CR, 23 of the responders (71.9%) met the criteria. All patients who achieved a CR maintained it for a mean duration of 507.4 days. Finally, 64% of persistent responders to monthly pegloticase also met criteria for CR.Conclusion. These results have validated the proposed remission criteria for gout and have helped define criteria for CR in individuals with chronic gout treated with pegloticase. This composite CR index can serve as an evidence-based target to inform the design and end points of future clinical trials.

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Outcome Measures for Gout Clinical Trials: a Summary of Progress

Cited by 7 publications

References 27 publications

2020 American College of Rheumatology Guideline for the Management of Gout

2020 American College of Rheumatology Guideline for the Management of Gout

Pyroptosis versus necroptosis: similarities, differences, and crosstalk

Evaluation of Proposed Criteria for Remission and Evidence‐Based Development of Criteria for Complete Response in Patients With Chronic Refractory Gout

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