https://research-information.bris.ac.uk/files/174223042/2018_Doherty_Lancet.pdf

Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial

Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial.

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the formation of plaques containing lipid, connective tissue and immune cells in the intima of large and medium-sized arteries. Over the past three decades, a substantial reduction in cardiovascular mortality has been achieved largely through LDL-cholesterol-lowering regimes and therapies targeting other traditional risk factors for cardiovascular disease, such as hypertension, smoking, diabetes mellitus and obesity. However, the overall benefits of targeting these risk factors have stagnated, and a huge global burden of cardiovascular disease remains. The indispensable role of immunological components in the establishment and chronicity of atherosclerosis has come to the forefront as a clinical target, with proof-of-principle studies demonstrating the benefit and challenges of targeting inflammation and the immune system in cardiovascular disease. In this Review, we provide an overview of the role of the immune system in atherosclerosis by discussing findings from preclinical research and clinical trials. We also identify important challenges that need to be addressed to advance the field and for successful clinical translation, including patient selection, identification of responders and non-responders to immunotherapies, implementation of patient immunophenotyping and potential surrogate end points for vascular inflammation. Finally, we provide strategic guidance for the translation of novel targets of immunotherapy into improvements in patient outcomes. In this Review, the authors provide an overview of the immune cells involved in atherosclerosis, discuss preclinical research and published and ongoing clinical trials assessing the therapeutic potential of targeting the immune system in atherosclerosis, highlight emerging therapeutic targets from preclinical studies and identify challenges for successful clinical translation. 

/pdf/therapeutic-strategies-targeting-inflammation-and-immunity-qcq6p2cq.pdf

Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?

This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management. New imaging tools are available, including US with key features and dual-energy CT rendering it able to reveal deposits of urate crystals. These deposits are now included in new diagnostic and classification criteria. Overall, half of the patients with gout are readily treated with allopurinol, the recommended xanthine oxidase inhibitor (XOI), with prophylaxis for flares with low-dose daily colchicine. The main management issues are related to patient adherence, because gout patients have the lowest rate of medication possession ratio at 1 year, but they also include clinical inertia by physicians, meaning XOI dosage is not titrated according to regular serum uric acid level measurements for targeting serum uric acid levels for uncomplicated (6.0 mg/dl) and complicated gout, or the British Society for Rheumatology recommended target (5.0 mg/dl). Difficult-to-treat gout encompasses polyarticular flares, and mostly patients with comorbidities, renal or heart failure, leading to contraindications or side effects of standard-of-care drugs (colchicine, NSAIDs, oral steroids) for flares; and tophaceous and/or destructive arthropathies, leading to switching between XOIs (febuxostat) or to combining XOI and uricosurics.

/pdf/gout-state-of-the-art-after-a-decade-of-developments-26ijneg960.pdf

Gout: state of the art after a decade of developments.

Objectives Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout and hyperuricemia. Design Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology. Data sources PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017). Eligibility criteria We included the latest version of international and national/regional clinical practice guidelines and consensus statements for diagnosis and/or treatment of hyperuricemia and gout, published in English or Chinese. Data extraction and synthesis Two reviewers independently screened searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid. Results Twenty-four guidance documents (16 clinical practice guidelines and 8 consensus statements) published between 2003 and 2017 were included. Included documents performed well in the domains of scope and purpose (median 85.4%, range 66.7%–100.0%) and clarity of presentation (median 79.2%, range 48.6%–98.6%), but unsatisfactory in applicability (median 10.9%, range 0.0%–66.7%) and editorial independence (median 28.1%, range 0.0%–83.3%). The 2017 British Society of Rheumatology guideline received the highest scores. Recommendations were concordant on the target serum uric acid level for long-term control, on some indications for urate-lowering therapy (ULT), and on the first-line drugs for ULT and for acute attack. Substantially inconsistent recommendations were provided for many items, especially for the timing of initiation of ULT and for treatment for asymptomatic hyperuricemia. Conclusions Methodological quality needs improvement in guidance documents on gout and hyperuricemia. Evidence for certain clinical questions is lacking, despite numerous trials in this field. Promoting standard guidance development methods and synthesising high-quality clinical evidence are potential approaches to reduce recommendation inconsistencies. PROSPERO registration number CRD42016046104.

https://bmjopen.bmj.com/content/bmjopen/9/8/e026677.full.pdf

Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements

/pdf/the-british-society-for-rheumatology-guideline-for-the-udgsk9893d.pdf

The British Society for Rheumatology Guideline for the Management of Gout.

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The British Society for Rheumatology Guideline for the Management of Gout.