PHAR3826 Gout Lecture 1 & 2 2024 PDF

Management of gout Presented by Dr Sophie Stocker [email protected] @drslstocker The University of Sydney Page 1 With thanks and acknowledgement to Prof Tim Chen  – Do you know someone with gout?...

Management of gout Presented by Dr Sophie Stocker [email protected] @drslstocker The University of Sydney Page 1 With thanks and acknowledgement to Prof Tim Chen  – Do you know someone with gout? Images: azpodiatrists.com; sciencephoto.com; verywellhealth.com; hss.edu The University of Sydney Page 2 Learning objectives – To understand the pathophysiology of gout – To understand the main treatment strategies for acute and preventative treatment – To be able to recommend pharmacotherapy for the acute management and prevention of gout The University of Sydney Page 3 Gout is an inflammatory arthritis – Gout is a crystalline arthropathy – Symptoms of joint pain, swelling and redness (gout flares) – Hyperuricaemia is the major risk factor for gout – Deposition of urate crystals in and around joints – Recurrent episodes of gout flares – Chronic arthropathy, tophi depositions, renal disease The University of Sydney Video from WebMD, “What Happens During a Gout Attack” 2019. Page 4 Accessed via YouTube. Gout is the most common inflammatory arthritis in men – Taiwanese Aboriginals/Maori/Pacific Islander prevalence >10% The University of Sydney Page 5 Dahlin et al Nature Rheumatol Reports 2020 The global prevalence of gout is rising – Gout prevalence increase >2-fold over the last 2 decades – In Australia – 6.8% prevalence, more common in men2 - Indigenous men have a higher prevalence of gout3 - Gout cost the healthcare system AU$203M in 20194 - AU$14M for pathology The University of Sydney (1) Safiri et al., Arthritis Rheumatol., 2020; (2) Pisaniello et al., Page 6 Arthritis Res. Ther. 2018; (3) AIHW, 2016; (4) AIHW, 2021 Burden of gout in Australia is high! – Increasing trend for the observed burden of gout globally The University of Sydney YLD = years lived with disability Page 7 Safiri et al Arthritis & Rheum, 2020 Pathophysiology & Aetiology – Disorder of purine metabolism – Hyperuricaemia (>0.42 mmol/L) – Overproduction of uric acid – Excessive cell turnover e.g. neoplastic disorders – Excessive dietary purines – Underexcretion of uric acid – Concomitant medications (e.g. loop/thiazide diuretics) – Obesity – Renal impairment – Uric acid reference range – Females 0.15-0.40 mmol/L – Males 0.20-0.45 mmol/L The University of Sydney Page 8  Underexcretion Overproduction of uric acid of uric acid Dietary purine urate Renal excretion load Endogenous purine synthesis Gut excretion Urate supersaturation & crystallisation (0.42 mmol/L) The University of Sydney Page 9 Gout Risk factors for gout – Hyperuricaemia – Male – Older age – Overweight – Family history – Renal impairment – Diet high in purines – e.g. beer, meat, shellfish – Use of diuretics Five-year cumulative incidence of gout according to serum uric acid level in men in the Normative Aging Study Roddy & Doherty Arthritis Research & Therapy 2010 The University of Sydney Page 10 Men have a greater risk of developing gout The University of Sydney Page 11 Kuo et al Nature Reviews Rheumatol 2015 Oder age is a risk factor for gout The University of Sydney Page 12 Dahlin et al Nature Rheumatol Reports 2020 Risk factors for gout – Genetics (family history) – Heritability: 35.1% in men 17.0% in women – Drug transporters involved in renal and gut clearance of uric acid e.g. SLC2A9, GLUT9 – Genetic variation accounts for only 7% of the variance in serum urate concentrations The University of Sydney Arthritis Research & Therapy 2010 Page 13 How is gout diagnosed? – Crystals in synovial fluid aspirates – Not performed regularly – Features are highly suggestive: – Articular involvement e.g. Toe or ankle joint – Previous similar acute arthritis episodes – Rapid onset of severe pain and swelling at its worst in 4 injections/year into any single joint - increases risk of cartilage damage – Avoid further injections if no response after 2 consecutive injections – Big toe generally not recommended due to pain – Do not overuse the joint following IA injection The University of Sydney Page 23 Indications for prophylactic treatment with urate lowering medicines – Tophaceous gout – Evidence of radiographic damage attributable to gout – 2 or more gout flares per year – Conditionally recommended for patients who have: – previously experienced >1 flare but have infrequent flares (< 2 p.a.) – Comorbid moderate to severe chronic kidney disease – Uroliathiasis The University of Sydney Page 24 Prevention of gout: urate lowering therapy – Xanthine oxidase inhibitors – reduce the production of uric acid – Allopurinol - preferred – Febuxostat – only if allopurinol contraindicated – Uricosuric agents – increase the renal clearance of uric acid – Probenecid – Benzbromarone (available via SAS) – Preferred concomitant medications – Drugs associated with a reduction in serum urate concentrations e.g. Losartan, fenofibrate, sodium–glucose cotransporter-2 (SGLT2) inhibitors The University of Sydney Page 25 The University of Sydney Page 26 Treat to target approach – Start at a low dose and up titrate based on serum urate concentrations – Measure serum urate regularly – at baseline (not during gout flare) – every 2–5 weeks during dose titration until target reached – every 6 months during maintenance – Aim: keep serum urate concentrations