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A scoping review that will synthesise clinical definitions of chronic refractory gout and identify treatment pathways for this condition.

Introduction Gout is a common, progressive, systemic inflammatory arthritis caused by hyperuricemia. Current guidelines recommend that serum uric acid (sUA) levels be maintained below 6.0 mg/dl to minimize acute gout attacks, tophi development, and long-term joint and organ damage. This study examined the influence of uncontrolled gout on post-diagnosis comorbidities and medication use. Methods The Humana Research Database (2007–2016, commercial insurance and Medicare) was searched (PearlDiver tool) for patients who had a gout diagnosis code, claims data for at least 6 months before and after diagnosis, and at least 90 days of continuous urate-lowering therapy within 1 year of diagnosis. Patients with controlled (all sUA measurements

Introduction The aim of this work is to evaluate the impact of the timing of pre-infusion serum uric acid (sUA) test results for use in applying stopping rules for pegloticase to identify patients at risk for infusion reactions (IRs) while on therapy. Methods Data from the phase 3 clinical trials of pegloticase were reviewed and individual uric acid levels of the 85 patients who received the approved regimen of biweekly infusions were examined in relation to the occurrence of IRs. Results Of the 22 patients (26%) who experienced an IR on pegloticase therapy without uric acid stopping rules, only seven (8%) would have had IRs if pegloticase therapy had been discontinued after two consecutive pre-infusion sUA levels above 6 mg/dl. If pegloticase therapy was stopped after a single pre-infusion sUA above 6 mg/dl, only two patients (2%) would have experienced IRs during the clinical studies. Conclusions A pre-infusion sUA level functions as a highly accurate biomarker for identification of patients who are at risk of IRs while on pegloticase therapy. Stopping pegloticase in patients who have a rise in pre-infusion uric acid levels to above 6 mg/dl while on therapy would result in most IRs being avoided. Funding Horizon Pharma.

Gout is a metabolic disorder of purine metabolism that results in crystallization of uric acid in the form of monosodium urate crystals, affects 8.3 million Americans and is the most common cause of inflammatory arthritis in adults. Urate lowering therapy is the mainstay of treatment for chronic gout. Initial treatments of choice in gout include allopurinol, a purine analog which inhibits xanthine oxidase and decreases the production of uric acid as well as probenecid which increases the urinary excretion of uric acid. However, 3% of patients will fail these treatments. In 2010, pegloticase, a recombinant urate oxidase conjugated to polyethylene glycol, was approved for these patients. Pegloticase has been shown to rapidly normalize plasma uric acid values, resolve tophi and improve quality of life in these patients. Hereby we present a case of a 50-year-old African male admitted to the hospital with symptomatic anemia 1 week after pegloticase infusion. He was found to have glucose-6-phosphate dehydrogenase deficiency, predisposing him to hemolytic anemia. Hereby we discuss his clinical course, and suggest glucose-6-phosphate dehydrogenase deficiency screening prior to pegloticase infusion.

Background In this paper we describe a novel method to achieve high yield bacterial expression of a small protein domain with considerable therapeutic potential; Domain I of Beta-2-glycoprotein I (β2GPI). β2GPI is intrinsic to the pathological progression of the Antiphospholipid Syndrome (APS). Patients develop autoantibodies targeting an epitope located on the N-terminal Domain I of β2GPI rendering this domain of interest as a possible therapeutic. Results This new method of production of Domain I of β2GPI has increased the production yield by ~20 fold compared to previous methods in E.coli. This largely scalable, partially automated method produces 50–75 mg of pure, folded, active Domain I of β2GPI per litre of expression media. Conclusion The application of this method may enable production of Domain I on sufficient scale to allow its use as a therapeutic.

Objectives:To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment.Methods:Prospective, multicentre, open-label, two-stage randomised controlled trial in gout patients with normal renal function. Enrolled patients were given 300 mg allopurinol for 2 months (stage 1). Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration (sUr) ⩽0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2).Results:96 patients were enrolled in stage 1. 82 patients (85%) were eligible for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr ⩽0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug reactions.62 patients were enrolled in stage 2. 27 patients received benzbromarone (3 patients not eligible for analysis) and 35 received probenecid (4 patients not eligible for analysis). Treatment with benzbromarone was successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (p = 0.03 compared with benzbromarone). Compared with baseline values, there was a mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid (pConclusion:This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr ⩽0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day.Trial registration number:ISRCTN21473387.