Psoriasis and Psoriatic Arthritis Treatment Guide PDF

Psoriasis Johnson Lee Pharmacy Guild NSW, Chief Pharmacist The University of Sydney Page 1  Learning outcomes Know the triggers for psoriasis and PsA Understand the pathogenesis of psoriasis and PsA Understand the bone alternation in PsA Recognise symptoms of psoriasis an...

Psoriasis Johnson Lee Pharmacy Guild NSW, Chief Pharmacist The University of Sydney Page 1  Learning outcomes Know the triggers for psoriasis and PsA Understand the pathogenesis of psoriasis and PsA Understand the bone alternation in PsA Recognise symptoms of psoriasis and PsA Identify psoriasis and PsA variants Appreciate treatments for mild/ moderate/ severe psoriasis Appreciate treatments for psoriasis in pregnancy Differentiate conventional DMARDs and biological treatments in PsA Know drug classes, names, and mode of action in PsA pharmacotherapy The University of Sydney Page 2  Background Psoriasis is an autoimmune disease that affects 2- 3% of the global population. A papulosquamous disorder characterised by: o Erythema (red inflammation) o Well demarcated (defined boundary) o Plaques with a silver scale (thick layer of skin) o papules (small round rash) Common sites include the scalp, elbows and knees, followed by the nails, hands, feet and trunk. Psoriasis was regarded as an epidermal disease in which the fundamental issue resided within the keratinocyte. Recent studies revealed the pathophysiology involves various classes of T cells and their interactions with dendritic cells and cells involved in innate immunity, e.g. neutrophils and keratinocytes. The University of Sydney Page 3  Triggers Psoriasis may result from genetic predisposition combined with environmental triggers. Triggers o Environmental: trauma, sunburn o Systemic: ✓ Bacterial streptococcal infections (e.g. pharyngitis, dental abscesses, perianal cellulitis, impetigo) ✓ Viral infections (HIV) o Metabolic/ endocrine disorder (hypocalcaemia) o Psychological stress (heightened cortisol response to stress, worrying and scratching) o Medications (lithium, IFNs, β-blockers, and anti-malarials, rapid taper of systemic corticosteroids) o Alcohol consumption, smoking and obesity The University of Sydney Page 4  Pathogenesis The University of Sydney Page 5 van de Kerkhof, Peter C.M.; Nestlé, Frank O..PublishedJanuary 1, 2018.Pages138-160.©2018.  Presentations Typical plaque psoriasis o Symmetric, well- demarcated plaques o Coarse with erythema o Pruritus (itch level may vary) o Pinpoint bleeding upon plaque removal (Auspitz sign) Skin lesions appearing in areas of local trauma (Koebner phenomenon) Common sites: extensor surfaces, scalp, and flexures (lesions in skin folds are not scaly) Nail changes o Pitting o Thickening o Onycholysis (nail elevation) o Subungual hyperkeratosis (chalky build up underneath nails) o Trachyonychia (long ridges) o Oil spots The University of Sydney Page 6  Psoriasis manifestations The University of Sydney Page 7 https://www-clinicalkey-com-au.ezproxy1.library.usyd.edu.au/#!/content/clinical_overview/67-s2.0-5c047fba-f19f-4a81-9c8e-ece9a4bf04b8  Comorbidities Higher risk of comorbidities: o Obesity o Cardiovascular disease (heart attack, stroke, hypertension) o Malignancy o Diabetes o Metabolic syndrome o Inflammatory bowel disease and other autoimmune conditions o Serious infections Psychosocial aspects: o Depression o Compliance issues The University of Sydney Page 8  Classifications of psoriasis Severity can be classified from mild to moderate or severe disease, with assessment based on: o Area coverage and plaque appearance graded by Psoriasis Area and Severity Index (PASI) and o Quality of life indicators graded by Dermatology Life Quality Index (DLQI) Classification: o PASI ≤ 10 and DLQI ≤ 10 (mild to moderate) o PASI > 10 and/or DLQI > 10 (severe) The psoriasis is always considered severe when DLQI (patient subjective) > 10, regardless of the PASI score (clinician objective). The University of Sydney Page 9  Treatment for mild/ moderate psoriasis Limited plaque psoriasis: o Topical corticosteroids and emollients o Vitamin D analogues (calcipotriol) o Topical retinoids (tazarotene) o Coal tar Facial or sensitive areas: o topical pimecrolimus may be used as corticosteroid sparing agents (improvement may not be as rapid) Resistant or extensive disease: o Phototherapy+ psoralen (non-PBS) o Limited by cost and time constraint The University of Sydney Page 10  Treatment for severe psoriasis Initially treated with phototherapy + topical therapies as adjuvant therapy and for symptomatic relief. For resistant disease commence systemic agents including: o Retinoids o Methotrexate (MTX) o Cyclosporine o Apremilast o Biologic DMARDs Erythrodermic psoriasis: o Cyclosporine or infliximab due to the rapid onset and high efficacy of these agents o Patients with less acute disease can be treated with acitretin or MTX o Systemic glucocorticoid is discouraged as it may exacerbate the condition upon withdrawal. The University of Sydney Page 11  Treatment in pregnancy Psoriasis may improve (40-60%) or worsen (10-20%) during pregnancy. o Increased progesterone hormone during pregnancy may reduce the autoimmune response. For limited psoriasis: o 1st line: low to medium potency topical corticosteroid (rather than systemic therapy). o Emollients for reducing bothersome scale. For resistant or extensive disease: o Consider localised phototherapy (rather than systemic therapy). o Because psoriasis often improves during pregnancy, women who required systemic treatment prior to pregnancy may be able to transition to phototherapy. Contraindicated: topical and systemic retinoids (tazarotene/acitretin), MTX. The University of Sydney Page 12  NSW Pharmacy Trial NSW Pharmacy Trial skin conditions authority includes S4 substances: ✓ Methylprednisolone ✓ Mometasone ✓ Betamethasone ✓ Clobetasol ✓ Calcipotriol with betamethasone Australian College of Pharmacy NSW Skin Conditions Course https://www.acp.edu.au/education/short-courses/skin- conditions/nsw/ Complimentary ACP membership https://www.acp.edu.au/_membership.join/form/typeid/1893 The University of Sydney Page 13  Differential diagnoses Seborrhoeic dermatitis The University of Sydney Page 14 https://dermnetnz.org/cme/dermatitis/seborrhoeic-dermatitis  Differential diagnoses Fungal infection o Tinea capitis oPityriasis versicolor https://dermnetnz.org/topics/tinea-capitis The University of Sydney Page 15 https://dermnetnz.org/topics/pityriasis-versicolor  Differential diagnoses – Pityriasis rosea The University of Sydney https://dermnetnz.org/topics/pityriasis-rosea Page 16 Psoriatic Arthritis Johnson Lee Pharmacy Guild NSW, Chief Pharmacist The University of Sydney Page 17  Psoriatic arthritis (PsA) PsA occurs in 5–30% of patients with cutaneous psoriasis. In 10–15% of patients the symptoms of psoriatic arthritis appear before involvement of the skin. PsA is more prevalent among patients with relatively severe psoriasis. Risk factors: initial presentation at an early age, female, genetic. PIP DIP The University of Sydney Page 18 https://www-clinicalkey-com-au.ezproxy1.library.usyd.edu.au/#!/content/book/3-s2.0-B9780702062759000088?scrollTo=%23hl0002442  PsA features Typically involves the nail bed, including nail pits and onycholysis. o Nail lesions occur in 80-90% of patients with PsA. o The severity of psoriatic nail involvement correlates with the extent and severity of both skin and joint disease. Laboratory findings in PsA: o Non-specific, acute phase bio-markers (CRP, ESR) are elevated in only about 40% of the patients. o No laboratory findings characteristic of PsA that distinguish it from other forms of inflammatory arthritis. o Radiographic changes: exhibit a pattern usually not seen in other forms of inflammatory arthritis, including the coexistence of erosive changes and new bone formation. The University of Sydney Page 19  PsA manifestations Oligoarticular peripheral arthritis- 50% of patients; involves up to 5 joints. Polyarticular peripheral arthritis- 30% of patients; involves >5 joints; may resemble rheumatoid arthritis. Predominant sacroiliitis and spondylitis- 10% of patients. Predominant DIP in both hands and feet- 5% of patients. The University of Sydney Page 20  Bone remodelling in PsA Osteoclastogensis Bone formation in enthesitis Cytokines drive osteoclast recruitment Inflammation triggers ligament cell Bone erosion recruitment and bone cell hypertrophy New bone formation and joint fusion The University of Sydney Page 21 https://bmcmusculoskeletdisord.biomedcentral.com/track/pdf/10.1186/s12891-020-03804-2.pdf  Treatment for peripheral PsA Mild arthritis– may be effectively treated by use of NSAIDs. Moderate/ severe arthritis or resistant to NSAIDs– usually treated with a conventional DMARD (eg. MTX, LEF, SSZ). o Apremilast may be useful for patients who wish to avoid DMARD therapy, although only a portion of patients respond. It should not be used in patients with erosive disease (no established evidence). Severe disease at presentation– biologic DMARD (eg. TNFi) as 1st line because of its capacity to limit joint damage and more rapidly restore function. Resistant to nonbiologic DMARD–introduce biologic DMARD, such as a TNF inhibitor. o An alternative biologic may be required in patients with an inadequate response to TNF inhibitors, eg. mABs and JAKi. The University of Sydney Page 22  Conventional Treatment MTX MTX: o Prior to Tx: liver function, hepatitis status, chest radiography. o 1st line in PsA, weekly dosing. o Folic acid; unsatisfactory response to folic acid or poor tolerance-folinic acid (day after MTX). o Monitor: CBC, liver, lungs. o Lack of responsiveness to MTX 25mg/week for 6-8wks are unlikely to respond to more prolonged therapy-consider TNFi. Other initial options: o Intolerant of or unresponsive to MTX/unwillingness: consider LEF (generally not beneficial for the skin disease). o Unable to take either MTX or LEF→ SSZ The University of Sydney Page 23  Treatment options Class Drug MOA Conventional DMARD Methotrexate folic acid analogue Leflunomide pyrimidine synthesis inhibitor Sulfasalazine anti-inflammatory and immunosuppression Hydroxychloroquine immunomodulatory Biological DMARD TNF-α Etanercept TNF-α inhibition Adalimumab Golimumab Infliximab Certolizumab interleukin target therapy Ustekinumab IL-12/23 inhibition Secukinumab IL-17A inhibition Anakinra IL-1 inhibition T-cell target therapy Abatacept CD28/CTLA4 costimulation blockage B-cell target therapy Rituximab B cell depletion Small molecules JAK pathway Tofacitinib JAK1/3 inhibition The University of Sydney Page 24  Treatment for severe PsA Erosive disease with functional limitation: TNFi 1st line, rather than a conventional non biologic DMARD. o Preferred as the TNFi and other biologic agents to limit joint damage and more rapidly restore function. If joint counts do not improve substantially after three months of treatment with a conventional synthetic DMARD (eg, MTX), or who still have more than three tender and swollen joints. o Use TNFi rather than sequential trials of other conventional DMARD. In patients with peripheral arthritis who experience an inadequate response to an initial TNFi, use a another TNFi rather than trying a different class of biologic agent. The University of Sydney Page 25  Treatment – resistant to TNFi – In patients who do not respond adequately to two different TNF inhibitors: use an IL- inhibitor. – Resistant to multiple biologics – consider another treatment class, e.g. T/B cell therapy. – JAK inhibitors are available in oral formulations and have demonstrated efficacy in the treatment of PsA in patients with an inadequate response to a conventional DMARD and patients with an inadequate response to TNFi. The University of Sydney Page 26  New safety warning on JAKi A large post marketing rheumatoid arthritis safety study of the JAK inhibitor tofacitinib found an increased risk of major cardiovascular problems, such as heart attack and stroke, cancer, blood clots, serious infections and death, as compared with TNFi. TGA guidance: JAK inhibitors should not be prescribed for at-risk patient groups unless there are no suitable alternatives: o those aged 65 years or above o those at increased risk of major cardiovascular problems (such as heart attack or stroke) o those who smoke or have done so for a long time in the past o those at increased risk of cancer The University of Sydney Page 27  Sample exam questions 1. Which one of the following is not a trigger for psoriasis? a. dendritic cell b. LL37 c. mast cell d. HIV 2. Which of the following statements is true? a. psoriasis is associated with a higher risk of inflammatory bowel disease b. the immunopathogensis of psoriasis involves LL37 directly activating T-helper cells b. psoriasis typically worsens during pregnancy c. psoriasis is not associated with depression 3. Which one of the following treatments is not a standard choice for mild psoriasis? a. calcipotriol b. UVB c. tazarotene d. cyclosporin 4. Which one of the following is a TNF-alpha inhibitor? a. golimumab b. rituximab c. denosumab d. tofacitinib The University of Sydney Page 28  Sample exam questions Name four drugs which belong to the group of conventional non-biologic DMARDs; and explain why biologic agents are considered first line treatment for severe psoriatic arthritis with erosive disease. (5 marks) 4 conventional DMARDs: 1. Methotrexate 2. Leflunomide 3. Sulfasalazine 4. Hydroxychloroquine Biologic agents preferred for severe PsA because they limit joint damage and restore function more rapidly than conventional DMARDs. The University of Sydney Page 29  COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING This material has been copied and communicated to you by or on behalf of the University of Sydney pursuant to Part VB of the Copyright Act 1968. (The Act). The material in this communication may be subject to copyright under the Act. Any further copying or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice. Osteoarthritis Dr Jonathan Penm [email protected] @JonPenm Learning objectives To know the epidemiology of osteoarthritis in Australia To know the definition of osteoarthritis To know the pathophysiology/aetiology of osteoarthritis To know the symptoms of osteoarthritis To know the rationale for treatments in osteoarthritis To know main counselling points in osteoarthritis Osteoarthritis Epidemiology Definition Pathophysiology/aetiology Symptoms Treatment Counselling Osteoarthritis In Australia: 9.3% (2.2. million) have osteoarthritis 62% of all arthritic conditions = osteoarthritis In Australian by age group: >45 years >75 years 22% 36% 78% 64% Osteoarthritis No osteoarthrit is Osteoarthritis No osteoarthrit is 2x more likely in women Australian Institute of Health and Welfare 2020 https://www.aihw.gov.au/reports/chronic-musculoskeletal-conditions/osteoarthritis/contents/what-is-osteoarthritis Osteoarthritis Chronic condition Breakdown of the cartilage that overlies the ends of bones in joints Bones rubbing together = pain, swelling and loss of motion Australian Institute of Health and Welfare 2020 https://www.aihw.gov.au/reports/chronic-musculoskeletal-conditions/osteoarthritis/contents/what-is-osteoarthritis Osteoarthritis Definition works for patients Focuses heavily on symptoms Doesn’t incorporate new biological understanding Definition – Osteoarthritis research society international: “Osteoarthritis is a disorder involving movable joints characterized by cell stress and extracellular matrix degradation initiated by micro- and macro-injury that activates maladaptive repair responses including pro-inflammatory pathways of innate immunity. The disease manifests first as a molecular derangement (abnormal joint tissue metabolism) followed by anatomic, and/or physiologic derangements (characterized by cartilage degradation, bone remodeling, osteophyte formation, joint inflammation and loss of normal joint function), that can culminate in illness” Australian Institute of Health and Welfare 2020 https://www.aihw.gov.au/reports/chronic-musculoskeletal-conditions/osteoarthritis/contents/what-is-osteoarthritis  Osteoarthritis Osteophyte = bony lump Kraus, V. B., Blanco, F. J., Englund, M., Karsdal, M. A., & Lohmander, L. S. (2015). Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthritis and cartilage, 23(8), 1233–1241. https://doi.org/10.1016/j.joca.2015.03.036 Osteoarthritis B. Microfracture/injury: ↑ Enzymes e.g. ADAMTS4,5 cleave proteoglycan (aggrecan) MMP-13 cleaves collagen II →Cartilage thins Remodelling of bone: Subchondral bone thickening (sclerosis) bony growth = osteophytes Synovial membrane lining layer hyperplasia inflammation (synovitis) leukocyte infiltration fibrosis F Medial joint space narrowing Goldman-Cecil Medicine Osteophyte at joint margins Twenty Sixth Edition Osteoarthritis MYTHS DEFINITION “osteoarthritis is due to wearing down of joint surfaces” initiated by micro- and macro-injury* that activates maladaptive repair responses including pro-inflammatory pathways of innate “osteoarthritis is an inevitable consequence of immunity. aging” *mechanical load that exceeds a defined injury threshold “damaged joints do not have the ability to repair themselves.” “non–weight-bearing joints do not get true involving movable joints (any joint) osteoarthritis” Risk factors Altered loading Obesity Joint injury/trauma Occupational and lifestyle (manual labour) Altered matrix (unprotected joint) Advancing age Family history (hand/hip) Female Australian Institute of Health and Welfare 2020 https://www.aihw.gov.au/reports/chronic-musculoskeletal-conditions/osteoarthritis/contents/what-is-osteoarthritis Joints commonly affected by osteoarthritis. Signs/Symptoms Bony swelling: Distal interphalangeal (DIP) joints = Heberden nodes Proximal interphalangeal (PIP) joints = Bouchard nodes Pain at joint May worsen with joint use Stiffness Stiffness following inactivity or morning stiffness ( Student login Room name: USYDPHARM Treatment First line treatments Weight control Therapeutic exercise Patient education Additional therapies Psychological therapies (eg cognitive behavioural therapy) Pharmacological Last resort Surgery (hip replacement, knee replacement etc.) Treatment Quality indicators – High quality care Meta-analysis showed Non-drug treatments – 36% pass rate Drug treatments – 38% pass rate Surgery – 79% pass rate OA treatment is suboptimal Weight control Recommended in all overweight/obese patients Regardless of joint affected ↑ % weight loss = ↑ improvement in symptom1 1% weight loss = 2% improvement in pain, function, and stiffness (WOMAC) Most effective weight loss on knee OA: Bariatric surgery = ↓ 62.7% knee pain Low calorie diet + exercise = ↓ 34.4% knee pain 1. Panunzi S, Maltese S, De Gaetano A, Capristo E, Bornstein SR, Mingrone G. Comparative efficacy of different weight loss treatments on knee osteoarthritis: A network meta-analysis. Obesity Reviews. 2021 Aug;22(8):e13230. Therapeutic exercise Exercise is recommended for all patients with OA irrespective of joint or or severity ↓ pain, and ↑ physical function and quality of life Adherence in long term > type of exercise patient's functional impairments, comorbidities, and activity preferences Some discomfort from exercise is common Topical or oral analgesia may be required to facilitate exercise Can refer to Physiotherapists or exercise physiologists Types of exercise Network meta-analysis on effectiveness of types of exercise: Combination of strength, aerobic and flexibility exercise is most likely to ↓ pain, and ↑ physical function Uthman OA, Van Der Windt DA, Jordan JL, Dziedzic KS, Healey EL, Peat GM, Foster NE. Exercise for lower limb osteoarthritis: systematic review incorporating trial sequential analysis and network meta-analysis. Bmj. 2013 Sep 20;347. Therapeutic exercise Myth = exercise causes harm Exercise is safe Use supportive / non-catastrophic language ‘hurt does not mean harm’ ‘sore but safe’ Avoid negative terms for OA e.g. ‘bone on bone’ ‘normal wear and tear’ ‘cartilage erosion’ Bricca A, Roos EM, Juhl CB, Skou ST, Silva DO, Barton CJ. Infographic. Therapeutic exercise relieves pain and does not harm knee cartilage nor trigger inflammation. British Journal of Sports Medicine. 2020 Jan 1;54(2):118-9. Patient education All patients should be educated on: Osteoarthritis likelihood of slow or minimal disease progression fluctuating nature of osteoarthritis symptoms poor correlation between symptoms and radiological findings modifiable risk factors for disease progression Advice on self-management Materials available at: Arthritis Australia - http://www.arthritisaustralia.com.au/ The ‘My Joint Pain’ program - https://www.myjointpain.org.au/ ‘painHEALTH’ program - https://painhealth.csse.uwa.edu.au/pain- module/osteoarthritis/ Patient education https://youtu.be/GDUMWPjN7Dk Pharmacological therapies 1st line - Topical NSAIDs and capsaicin 2nd line - Paracetamol and oral NSAIDs 3rd line - Intra-articular injections - Duloxetine Topical NSAIDs and capsaicin Topical have some benefit Topical = minimal absorption = safer than oral 1. NSAID 2. Capsaicin – releases and depletes substance P Paracetamol and oral NSAIDs NSAIDS more effective than paracetamol ↑ side effects (particularly elderly) Only use NSAID before paracetamol if low risk of harm from NSAID Osteoarthritis symptoms can fluctuate If symptoms improve, can trial ceasing oral analgesia Intra-articular injections Intra-articular corticosteroids injections - ↓ pain and inflammation Rapid relief for short term only Allow participation of strengthening exercises / other events Use every 3 months prn Betamethasone usually smaller joints Methylprednisolone acetate is crystalline usually larger joints Triamcinolone acetonide - least soluble longest duration of action, up to 21 weeks Intra-articular injections Intra-articular corticosteroids doses Intra-articular hyaluronic acid (natural lubricant in synovial fluid) evidence is conflicting Duloxetine Inhibit serotonin and noradrenaline reuptake Similar efficacy to oral NSAIDS Lack head to head studies Unknown place in therapy Side-effect profile Nausea, dry mouth, constipation Weakness, sexual dysfunction Somnolence, insomnia Headache, blurred vision Tremor, tachycardia, bleeding Surgery Osteotomy = cuts/reshapes bone Arthroplasty = joint replacement (with artificial joint) Regular opioid use before surgery = worse surgical outcomes In Osteoarthritis: poor evidence for opioid use No benefit Many harms Taper opioids before surgery?  Infographic Levine BR. Osteoarthritis. The Infographic Guide to Medicine, 10 September 2021. McGraw Hill, 2021. AccessMedicine* *Treatment updated to reflect TGs Weight loss/exercise Patient education Topical NSAIDs and capsaicin Paracetamol and oral NSAIDs Intra-articular injections Duloxetine Surgery (osteotomy, arthroplasty)  Class questions Download Socrative app or visit www.socrative.com > Student login Room name: USYDPHARM  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