The epigenome: key to understanding and predicting gout flares

Pathology ◽  
2021 ◽  
Author(s):  
Ben Wolyncewicz ◽  
Tanya J. Major ◽  
Brett Delahunt ◽  
Michelle Thunders
Keyword(s):  
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 460.1-461
Author(s):  
B. Pouls ◽  
C. Bekker ◽  
B. Van den Bemt ◽  
A. Gaffo ◽  
M. Flendrie

Background:Gout flares are considered a key clinical and research outcome in gout. Early treatment of gout flares increases patient well-being and warrants timely notification of the treating clinician.Objectives:To test the feasibility of a smartphone app to home-monitor gout flares real-time for both patients with a suspicion of and established gout.Methods:Thirty patients were recruited during their visit at the outpatient rheumatology clinic. Inclusion criteria were age ≥ 18 years, smartphone possession, established gout (crystal proven) or a clinical suspicion of gout and at least one flare reported in the last three months.A straight-forward query app was used to incorporate an adapted version of the 2017 four-criteria gout flare definition.[1] For 90 consecutive days the app asked patients to report their current pain score on an 11-points scale as screening question. Scoring pain below 4 terminated the query, otherwise the app posed the remaining criteria: does the patient experience warm and/or swollen joints and are symptoms regarded as a gout flare. Responses were transmitted in real-time to the dashboard and the clinician was alerted via email if predefined conditions were met. End of study evaluation consisted of the number of generated alerts, duration of (possible) flares and actions taken. Patient feasibility was assessed by measuring app attrition and using a questionnaire based on the Technology Acceptance Model. [2] All constructs were analysed using descriptive statistics.Results:All 30 recruited patients finished the trial. Three minor, resolvable technical issues were reported. Seventeen participants never missed a question. In total 110 responses (4.1%) were missed with three participants responsible for 66 missings. 90% of the participants rated app usability good to excellent and 70% would recommend the app to other patients.Twelve out of thirty patients generated a total amount of 174 alerts where four patients with a suspicion of gout were responsible for 148 alerts (85%). These patients scored three out of four criteria as they had warm, swollen and painful joints but, after consultation with the clinician, their symptoms were not regarded as a gout flare.The 174 alerts belonged to 23 (possible) flares with a median duration of 5 days [IQR 3,5 – 7,5]. Twenty-one pro-active telephone calls were made which resulted in four visits to the clinic within 48 hours. Clinical guidance over the phone consisted of checking in on patient’s symptoms, giving advice and ten medication adjustments.Conclusion:This prospective study shows feasibility of a smartphone app for home-monitoring gout flares for patients because of high usability scores and low attrition rates. The app has added value for gout care because it enables clinicians to act on flares as they occur. The next step is to further implement the app whilst perpetuating investigation into the added value for patients and clinical practice alike.References:[1]Gaffo AL, Dalbeth N, Saag KG, et al. Brief Report: Validation of a Definition of Flare in Patients With Established Gout. Arthritis Rheumatol. 2018;70(3):462-467.[2]Davis Jr. FD. A Technology Acceptance Model for empirically testing new end-user information systems: theory and results. MIT PhD thesis. 1985[3]Stoyanov SR, Hides L, Kavanagh DJ, Wilson H. Development and Validation of the User Version of the Mobile Application Rating Scale (uMARS). JMIR Mhealth Uhealth. 2016;4(2):e72.Acknowledgements:This study was funded by AbbVie and Menarini.Disclosure of Interests: :Bart Pouls: None declared, Charlotte Bekker: None declared, Bart van den Bemt Grant/research support from: UCB, Pfizer and Abbvie, Consultant of: Delivered consultancy work for UCB, Novartis and Pfizer, Speakers bureau: Pfizer, AbbVie, UCB, Biogen and Sandoz., Angelo Gaffo Grant/research support from: Received a research grant from AMGEN, Marcel Flendrie Grant/research support from: M. Flendrie has received grants from Menarini and Grunenthal., Consultant of: M. Flendrie has received consultancy fees from Menarini and Grunenthal.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 442.2-443 ◽  
Author(s):  
H. Rainey ◽  
H. S. B. Baraf ◽  
A. Yeo ◽  
P. Lipsky

Background:Pegloticase is a mammalian recombinant uricase coupled to monomethoxy polyethylene glycol that is approved in the US for treatment of patients with chronic refractory gout and causes profound reductions in serum urate. However, treatment with pegloticase is limited by the induction of anti-drug antibodies and loss of responsiveness in nearly half of treated patients.Objectives:The goal of this study was to determine whether co-therapy with azathioprine (AZA) would increase the frequency of chronic refractory gout patients who had persistent urate lowering from pegloticase therapy.Methods:This open label multicenter study enrolled subjects with chronic gout who failed to lower serum urate to <6 mg/dL despite medically indicated doses of urate lowering therapy (NCT02598596). Patients were screened for adequate levels of the AZA metabolizing enzyme thiopurine methyl transferase and then started on daily oral AZA 1.25 mg/kg for 1 week and then 2.5 mg/kg for the remainder of the trial. Blood levels of AZA metabolites 6-thioguanine and 6-methylmercaptopurine were measured biweekly. After receiving 2 weeks of AZA, patients were started on pegloticase (8 mg IV) and were treated biweekly for 24 weeks. The primary endpoint was the persistent lowering of serum urate to <6 mg/dL at the last three consecutive study visits. Patients who had an increase in serum urate to >6 mg/dL while on therapy did not receive additional pegloticase. All patients received infusion prophylaxis with hydrocortisone as well as gout flare prophylaxis.Results:To date, 12 patients have been enrolled. All patients were male, 75% white and 25% African American. Mean age was 62.4 ± 14.7 years, the mean BMI was 31.1 ± 4.5 and the mean duration of gout was 13.8 ± 9.2 years. At baseline, all patients had visible tophi; 58.3% suffered from gout flares; 81.8% had hypertension; 45.5% had dyslipidemia and 9.0% had coronary artery disease. Of the 12 patients, 6 have completed the full course of treatment with persistent urate lowering and 2 remain on treatment also with persistent urate lowering (figure). 2 patients lost the urate lowering effect, both after 2 doses of pegloticase, and did not receive additional therapy. 1 patient experienced an infusion reaction during the first dose (1 infusion reaction in 90 infusions [1.1%] in the entire trial to date) and 1 subject had subjective symptoms of AZA intolerance with no laboratory abnormalities; these subjects discontinued the study and were not evaluable for the endpoint. No adverse events related to AZA were reported and gout flares were noted in 6 subjects (mean 1.5 flares/patient with flares).Conclusion:AZA can be used safely in subjects with chronic refractory gout and appears to increase the frequency of subjects experiencing long term lowering of serum urate.References:Disclosure of Interests: :Hope Rainey: None declared, Herbert S.B. Baraf Grant/research support from: Horizon; Gilead Sciences, Inc.; Pfizer; Janssen; AbbVie, Consultant of: Horizon; Gilead Sciences, Inc.; Merck; AbbVie, Speakers bureau: Horizon, Anthony Yeo Employee of: Horizon, Peter Lipsky Consultant of: Horizon Therapeutics


Drugs & Aging ◽  
2017 ◽  
Vol 34 (12) ◽  
pp. 873-880 ◽  
Author(s):  
Abhishek Abhishek
Keyword(s):  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 446.2-446
Author(s):  
L. Brunetti ◽  
J. Vekaria ◽  
P. Lipsky ◽  
N. Schlesinger

Background:Gout is the most common form of inflammatory arthritis and its economic burden is substantial, with estimates for the overall cost exceeding $20 billion (US) annually. Contributing to the economic burden are hospital admissions and iatrogenic events associated with pharmacotherapy. Identification of modifiable risk factors would be an important contribution to clinical practice.Objectives:The aim of this study was to identify opportunities for enhancing gout care in patients presenting to the Emergency Department (ED) with gout flares.Methods:This retrospective cohort study used data from electronic medical records (EMR) at a large community hospital. All consecutive patients visiting the medical center ED with a primary diagnosis of gout from 1/1/2016 to 7/1/2019 were included. Patients were then followed for 90 days to determine whether they were readmitted to the ED for any reason. A chart review identified whether they were on appropriate medications in terms of gout flare management. All data were summarized using descriptive statistics. A multiple logistic regression was constructed to identify risk factors for ED utilization within 90 days of the index visit.Results:A total of 214 patients were included in the analysis. Most patients were male (79%), mean age was 59.4 ± 15.6 years, and mean Charlson comorbidity index was 0.5 ± 1.14. The most common medications prescribed during the ED visit included NSAIDs (41.6%), opioids (28%), corticosteroids (26.6%), and colchicine (21%). Allopurinol and febuxostat were initiated in the ED in 4.7% and 0.9%, respectively. Discharge medications for the management of gout included NSAIDs (37%), corticosteroids (34.6%), opioids (23.8%), colchicine (14%), febuxostat (7%), and allopurinol (6.5%). Of the patients sent home with an opioid, 40% were newly prescribed. An anti-inflammatory medication was not prescribed in 29.6% of patients discharged from the ED. Readmission within 90 days was recorded in 16.8% of patients. Of these readmissions, 33.3% were gout-related and 11.1% were cardiac related.After adjusting for age and comorbidity index, patients receiving colchicine were 2.8 times more likely (OR, 2.81; 95% CI, 1.12 to 7.02; p=0.027) to return to the ED within 90 days. The most common cause of readmission in this subset was gout-related (54.5%).Conclusion:Nearly 30% of patients were discharged from the ED without an anti-inflammatory medication, whereas initiation of urate lowering therapy was rare. Opiates were used frequently, but the indication was uncertain. Only 5.6% of subjects revisited the ED for gout-related diagnoses in the subsequent 3 months. Colchicine prescription was associated with an increased risk of gout-related ED utilization within 90 days. Treatment of gout in the ED is sub-optimal and often does not follow established guidelines.Disclosure of Interests: :Luigi Brunetti Grant/research support from: Astellas Pharma, CSL Behring, Consultant of: Horizon Foundation of New Jersey, Janaki Vekaria: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon


2018 ◽  
Vol 46 (7) ◽  
pp. 748-750 ◽  
Author(s):  
Julianna Desmarais ◽  
Cong-Qiu Chu

Objective.To evaluate the efficacy and safety of anakinra in inpatient management of acute gout and pseudogout.Methods.Hospitalized patients with acute gout (n = 77) or pseudogout (n = 11) or both (n = 3) were analyzed for response to anakinra and adverse effects.Results.Half of all patients had comorbidities limiting the treatment choice. Anakinra was well tolerated, and 92% of gout flares and 79% of pseudogout flares responded to treatment.Conclusion.Anakinra is an effective and safe treatment for acute gout and pseudogout in hospitalized patients, particularly in those with comorbidities.


2021 ◽  
Author(s):  
Talita Gonçalves Pereira De Souza ◽  
Ana Beatriz Vargas dos Santos ◽  
Geraldo da Rocha Castelar Pinheiro ◽  
Guilherme Brezenski Rodrigues ◽  
Elisa Henriques Benício ◽  
...  

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