Clinical Updates on the Management of Gout

Clinical Updates on the Management of GOUT Evidence-Based Strategies for Improved Patient Outcomes

Learning Objectives • Describe the pathophysiologic underpinnings of gout, with a focus on urate metabolism and excretion • Differentially diagnose gout based on hyperuricemia, joint assessment, podagra, and relevant risk factors • Discuss current and emerging treatment strategies that can reduce hyperuricemia and risks of acute gout attacks • Tailor treatment regimens for patients with gout based on disease severity, renal function, therapeutic response, and comorbid conditions • Engage patients in open dialogue about gout as a chronic disease, treatment expectations and options, and the importance of treatment adherence

Gout Is Common •

Affects ~8.3 million adults (3.9%) in the United States – Most common inflammatory joint disease in men – Disparity between men and women decreases after menopause • Loss of uricosuric effect of estrogen

•

Incidence/prevalence has increased over the last 40 years – Aging population – Higher rates of comorbidities linked to hyperuricemia • eg, obesity – Use of thiazide and loop diuretics – Dietary trends

Doherty M. Rheumatology. 2009;48(suppl 2):ii2–ii8; Lawrence RC, et al. Arthritis Rheum. 2008;58:26-35; Zhu Y, et al. Arthritis Rheum. 2011;63:3136-3141.

Silent tissue urate crystal deposition begins

Urate Burden

Pain Level

Gout 4 Stages of a Chronic Disease

Years Asymptomatic Hyperuricemia

Acute Gout With Intercritical Periods

Advanced Gout

Elevated serum urate with no clinical gout

Acute inflammation and intervals between flares

Long-term gouty complications of uncontrolled hyperuricemia

Perez-Ruiz F, et al. Adv Ther. 2015;32:31-41.

Scientific Insights Into GOUT Pathophysiology Michael H. Pillinger, MD Professor of Medicine Rheumatology Program Director NYU Langone Medical Center NYU Hospital for Joint Diseases Section Chief, Rheumatology Manhattan VA Hospital New York, New York 5

Urate Homeostasis Summary •

Uric acid is a product of purine metabolism

•

Gout develops in the presence of hyperuricemia – Many patients with hyperuricemia do not develop gout

•

Serum urate levels determined by: – Dietary purine intake – Cellular degradation of purines to urate (xanthine oxidase) – Urate excretion from the body via intestines and kidneys (most common etiologic mechanism)

•

Urate saturation (>6.8 mg/dL) can lead to monosodium urate crystals – Induce painful inflammatory responses – Grow into tophi – Precipitate erosive joint damage over time

Gustafsson D, Unwin R. BMC Nephrol. 2013;14:164.

Adam Patient Presentation • 52-year-old Thai-American accountant

• BMI, 27.8 kg/m2 • BP, 124/82 mm Hg

• Presents with intense pain in his right • Nonsmoker ankle • Medical history – Pain is 9/10 and severely limiting – Hypertension diagnosis mobility 4 years ago – 3 similar attacks in last 5 years • Lisinopril/hydrochlorothiazide • Self-limiting and “nothing to 20 mg/12.5 mg daily bother a doctor about” – T2DM diagnosis 1 year ago • Metformin 1000 mg twice daily

What would confirm or rule out a gout diagnosis?

BMI = body mass index; BP = blood pressure; T2DM = type 2 diabetes mellitus.

1977 ACR Criteria for Classification of Acute Gout Inadequate for Definitive In-Office Diagnosis 1.

>1 attack of acute arthritis

8.

Tophus (proven or suspected)

2.

Maximum inflammation developed within 1 day

9.

Hyperuricemia •

During acute gout flares, serum urate levels are 6.0 mg/dL in 14% and 8.0 mg/dL in 32% of cases

3.

Monoarthritis attack

4.

Redness observed over joints

5.

First MTP joint painful or swollen

10.

Asymmetric swelling within joint on x-ray

6.

Unilateral first MTP joint attack

11.

7.

Unilateral tarsal joint attack

Subcortical cysts without erosions on x-ray

12.

Joint fluid negative for infection

≥6 of the 12 criteria = probable gout MISDIAGNOSIS in 1 of 5 cases ACR = American College of Rheumatology; MTP = metatarsophalangeal.

Malik A, et al. J Clin Rheumatol. 2009;15:22-24; Schlesinger N, et al. J Rheumatol.

2009;36:1287-1289; Underwood M. BMJ. 2006;332:1315-1319; Wallace SL, et al.

Arthritis Rheum. 1977;20:895-900.

Common Sites of Acute Flares • Gout can occur in bursae, tendons, and joints • 80% of first attacks are monoarticular

Olecranon bursa Elbow Wrist Fingers

First MTP 50% of initial attacks Eventually affected in ~90% of patients Midfoot Grassi W, De Angelis R. Reumatismo. 2011;63:238-245; Terkeltaub R, Edwards NL. Gout: Diagnosis and Management of Gouty Arthritis and Hyperuricemia. 2nd ed. West Islip, NY: Professional Communications, Inc; 2011; Underwood M. BMJ. 2006;332:1315-1319.

Knee

Ankle Subtalar

Joint Aspiration and Synovial Fluid Analysis Best Measure for Definitive Diagnosis of Gout Gold Standard:

Compensated Polarized Light Microscopy • Urate crystals identified by: – Strong negative birefringence – Needle and rod shapes • Infection and crystals can be seen together • Helps rule out other causes – eg, rheumatoid arthritis, pseudogout ACR. Rheumatology Image Bank. Atlanta, GA; 1998; Phelps P, et al. JAMA. 1968;12;203:508-512.

Joint Aspiration Ideal vs Practical

Ideal Definitive diagnosis of gout achieved by joint aspiration in each patient

Common Practice PCPs and patients reluctant to aspirate inflamed joints Performed in approximately 10% of gout cases

PCPs = primary care providers.

Segal JB, et al. Arthritis Care Res. 1999;12:376-380; Swan A, et al. Ann Rheum Dis. 2002;61:493-498; Underwood M. BMJ. 2006;332:1315-1319; Wallace SL, et al.

Arthritis Rheum. 1977;20:895-900.

Imaging Urate Crystal Deposits and Tophaceous Gout

Plain X-ray

Ultrasound

CT Scan

MRI

Insensitive in early disease

Sensitive in early disease Can be abnormal in asymptomatic hyperuricemia

Sensitive, but expensive Dual-energy CT scans are specific for tophi

Sensitive, but expensive

CT = computed tomography; MRI = magnetic resonance imaging.

Schlesinger N. Am J Manag Care. 2005;11(suppl 15):S443-S450.

Major Alternatives in the Differential Diagnosis • • • •

Septic arthritis Pseudogout Cellulitis Osteoarthritis of first MTP joint or nodal osteoarthritis of small hand joints • Rheumatoid arthritis (vs chronic tophaceous gout) • Psoriatic arthritis, spondyloarthropathy • Lyme disease – Limited flares of painful oligoarthritis, typically involving the knee

Mease PJ. J Rheumatol. 2011;38:557-561.

Adam Diagnosis • Lipids • Pain came in the last 24 h – TC, 184 mg/dL – Redness over affected joint – LDL-C, 105 mg/dL – No tophi evident on exam – HDL-C, 45 mg/dL • No history of urolithiasis – TG, 172 mg/dL • Notable family history • CKD (stage 2) – Father, fatal MI at age 64 – eGFR, 80 mL/min/1.73 m2 – Mother, relatively healthy at age 88 – UACR, 4.2 mg/mmol • FPG, 102 mg/dL • Serum urate, 8.0 mg/dL

Adam receives a diagnosis of gout CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; FPG = fasting plasma glucose; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; MI = myocardial infarction; TC = total cholesterol; TG = triglycerides; UACR = urine albumin-creatinine ratio.

2012 ACR Gout Guidelines Pharmacologic Therapy for Acute Flares Assess Severity

Polyarticular or multiple large joints with severe pain

Mild/moderate pain or 1-3 small or 1-2 large joints

Monotherapy NSAIDs Most can be used at maximum approved doses Monitor for toxicities • • •

Combination Therapy • Colchicine + NSAID • Oral corticosteroid + colchicine • Intra-articular steroids with all other modalities

Systemic Corticosteroids Prednisone or prednisolone >0.5 mg/kg/d for 5-10 days

Colchicine 1.2 mg initially and 0.6 mg 1 hour later (fewer side effects than higher doses)

Supplement with topical ice as needed Initiate therapy within 24 h of acute gout flare onset Continue pharmacologic urate-lowering therapy during acute attacks

NSAID = nonsteroidal anti-inflammatory drug.

Khanna D, et al. Arthritis Care Res. 2012;64:1447-1461; Terkeltaub RA, et al. Arthritis Rheum. 2010;62:1060-1068.

2012 ACR Gout Guidelines Pharmacologic Therapy for Acute Flares (cont’d) Inadequate responsea Consider alternative diagnosis

Alternative Monotherapy

Treatment Outcome

Combination Add-on Therapy

Treatment Outcome

Successful outcome

Inadequate response

Off-Label Therapies in Development aInadequate

response defined as <20% improvement in pain within 24 h or <50% improvement after 24 h.

Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1447-1461.

Successful outcome

Patient Education • Diet and lifestyle triggers • Prompt self-treatment of subsequent attacks Urate-Lowering Therapy • Consider indications • Adjust ongoing regimen

ACR 2012 Gout Guidelines After the Initial Acute Attack…

• • • •

Counsel on factors that can precipitate attack Implement diet and lifestyle changes to prevent flares Consider secondary causes of hyperuricemia Eliminate nonessential medications that induce hyperuricemia • Evaluate gout disease burden – Palpable tophi – Frequency and severity of acute and chronic symptoms • Assess and encourage adherence with medications – Review dosing schedule, instructions, potential adverse events Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446; Zhang Y, et al. Ann Rheum Dis. 2012;71:1448-1453.

2012 ACR Gout Guidelines General Health, Diet, and Lifestyle Recommendations • Weight loss for obese patients (to BMI that promotes general health) • Healthy overall diet Avoid

• Exercise (to physical fitness) • Smoking cessation • Stay well hydrated Limit

Encourage

• Organ meats high in purine content (eg, sweetbreads, liver, kidney)

Serving sizes of: • Beef, lamb, pork • Seafood with high purines (eg, shellfish)

Low-fat or non-fat dairy products

• High-fructose corn syrup–sweetened sodas, other beverages, or foods

• Serving of naturally sweet fruit juices • Table sugar, sweet beverages, and desserts • Table salt, including in sauces

Vegetables

• Alcohol overuse (>2 drinks/day for men or >1 drink/day for women) • Any alcohol use during periods of frequent attacks or in poorly controlled advanced gout

• Alcohol (particularly beer, but also wine and spirits) in all patients

Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446; Zhang Y, et al. Ann Rheum Dis. 2012;71:1448-1453.

2012 ACR Gout Guidelines Comorbidity Checklist for Primary Care • Obesity and diet, including excessive alcohol intake • Modifiable risk factors for coronary artery disease or stroke – eg, hyperlipidemia, hypertension, metabolic syndrome, T2DM • Serum urate–elevating medications • History of urolithiasis • Chronic kidney glomerular or interstitial disease • Genetic cause of uric acid overproduction – Abnormal purine metabolism • Acquired cause of uric acid overproduction – Psoriasis, myeloproliferative or lymphoproliferative disease • Lead intoxication

Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446.

Adam Treatment of Acute Gout Flare • Acute regimen – Prescribed colchicine 1.2 mg initially and 0.6 mg 1 hour later – Advised to rest joint and apply ice as needed – Pain reduced to a tolerable level within 24 h • Provided with patient education materials on gout, including websites – Urate burden of a chronic disorder – “Curable” disease www.GoutEducation.org • Educated on dietary recommendations • Reminded of ongoing efforts to lose weight and adhere to his weekly exercise regimen

2012 ACR Gout Guidelines Indications for Pharmacologic Urate-Lowering Therapy

Tophus or Tophi Assess via clinical exam or imaging

Frequent Attacks â&#x2030;Ľ2 attacks of acute gouty arthritis/year

Chronic Kidney Disease Stage 2 or worse

History of Urolithiasis

Other patients may also be candidates for urate-lowering therapy Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446.

2012 ACR Gout Guidelines Current Recommendations for Urate-Lowering Therapy

Treat to individualized serum urate targets • The usual serum urate target is <6.0 mg/dL • Serum urate levels <5.0 mg/dL may be needed to improve gout signs and symptoms

Select First-Line Agent

Acute Gout Prophylaxis

Xanthine Oxidase Inhibitor

Initiate concomitant pharmacologic gout attack prophylaxis

Allopurinol

OR

Febuxostat

If ≥1 xanthine oxidase inhibitor is contraindicated or not tolerated

Alternative First-Line Agent

Probenecid

Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446.

2012 ACR Gout Guidelines Initiating Urate-Lowering Therapy • Do not start urate-lowering therapy during an attack unless good prophylaxis is in place – Fluxes in urate levels can precipitate acute flares • Increased surveillance necessary for gout determinantsa • Monitor regularly until serum urate target is achieved – Incidence of flares and serum urate levels decline over time with effective treatment • Timing is important – Adherence to urate-lowering therapy is often poor, especially in the first year aTophi,

recurrent attacks, very high serum urate levels, associated risk factors.

Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446.

2012 ACR Gout Guidelines Allopurinol as First-Line Urate-Lowering Therapy • Effective in uric acid overproducers and underexcretors • Published efficacy/safety data for doses ≥300 mg limited • Maximum FDA-approved dose, 800 mg/d – Reduced in CKD • Start at ≤100 mg/d (50 mg/d with severe CKD) – Gradual dose escalation every 2 to 5 weeks to reduce flare risk – Twice daily dosing for doses >300 mg to avoid GI side effects • Check renal and liver function before and during treatment FDA = US Food and Drug Administration; GI = gastrointestinal.

Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446; Terkeltaub R. Nat Rev Rheumatol. 2010;6:30-38.

Allopurinol Limitations as Urate-Lowering Therapy • Intolerance in 5%-10% (eg, liver function, GI, CNS) • Pruritic rash in ~2% • Major allopurinol hypersensitivity syndrome – Incidence 0.1%-0.4% (~25% mortality) – Usually in first months of therapy – More common with CKD, thiazides, HLA-B*5801 • Consider pharmacogenetic HLA-B*5801 PCR testing in high-risk populations (Han Chinese, Thai, Koreans) CNS = central nervous system; PCR = polymerase chain reaction.

Chao J, et al. Curr Rheumatol Rep. 2009;11:135-140; Hande KR, et al. Am J Med. 1984;76:47-56; Hung SI, et al. Proc Natl Acad Sci USA. 2005;102:4134-4139.

Allopurinol Dosing Current Usage vs Suggested Needs

Treated Patients, %

70

372 mg/daya

Predicted optimal dosing

60

Current dosing

50 40 30 20 10

100

300

500

Allopurinol Dose, mg/day aMean

dose required to achieve urate targets (<6.0 mg/dL) in small study of 49 patients with gout.

Perez-Ruiz F, et al. Ann Rheum Dis. 1998;57:545-549; Sarawate CA, et al.

Mayo Clin Proc. 2006;81:925-934.

700

Urate-Lowering Therapy Febuxostat • Selective inhibitor of xanthine oxidase with nonpurine backbone • Dose: 40 mg/d starting dose, labeled use up to 80 mg/d – ACR guidelines allow for doses up to 120 mg (approved in Europe) • Advantages – More selective than allopurinol – Lower renal excretion vs allopurinol active metabolite – No dose adjustment with mild/moderate renal or hepatic impairment • More expensive but well-tolerated alternative to allopurinol Khanna D, et al. Arthritis Care Res (Hoboken). 2012;64:1431-1446; Drugs@FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021856s006lbl.pdf. Accessed May 30, 2015.

Febuxostat Phase 3 Trials Patients With Serum Urate Levels <6.0 mg/dL at Final Visit, %

100 90

Febuxostat (40 mg/d)

80

28

Placebo

a 74%

60 50

45%

42%

40

c 39%

36%

30 20 10

n = 127 n = 757 n = 756 n = 756

n = 253 n = 263

0 CONFIRMS (6 mo)

aP

Allopurinol (300 mg/d)

b 72%

a 67%

70

Febuxostat (80 mg/d)

APEX (6 mo)

1%

n = 249 n = 242 FACT (12 mo)

<.001 vs allopurinol; bP <.05 vs placebo and vs allopurinol; cP <.05 vs placebo.

APEX = Allopurinol- and Placebo-Controlled, Efficacy Study of Febuxostat; CONFIRMS = Efficacy and Safety of Oral Febuxostat in Participants With Gout; FACT = Febuxostat Versus Allopurinol Control Trial.

Becker MA, et al. Arthritis Res Ther. 2010;12:R63; Becker MA, et al. N Engl J Med. 2005;353:2450-2461; Schumacher HR Jr, et al. Arthritis Rheum. 2008;59:1540-1548.

Urate-Lowering Therapy Uricosurics • Increase urate excretion by inhibiting urate reabsorption in the kidney • Probenecid—only FDA-approved uricosuric – Alternative in those intolerant to at least 1 xanthine oxidase inhibitor – Not recommended in persons with history of urolithiasis • Increases urolithiasis risk, especially with acidic urine pH – Not recommended if creatinine clearance <50 mL/min • Losartan, atorvastatin, and fenofibrate are less potent (and off-label) Khanna D, et al. Arthritis Care Res. 2012;64:1431-1446; Terkeltaub R. Arthritis Res Ther.

2009;11:236; Terkeltaub R, et al. Joint Bone Spine. 2009;76:444-446; Terkeltaub RA. N Engl J Med. 2003;349:1647-1655.

Urate-Lowering Therapy for Refractory Disease Pegloticase 14

Mean Plasma Uric Acid, mg/dL

Month 3

Respondersa Nonresponders Placebo

12

Month 6

10 8 6 4 2 0 1

3

5

7

9

11

13

Week

15

17

19

21

23

25

•

Drug antigenicity may cause loss of drug effect and infusion reactions

•

Stop oral urate-lowering therapy to avoid masking antibody-mediated loss of urate-lowering effect by pegloticase

aPositive

response defined as plasma urate levels <6.0 mg/dL for ≥80% of the time during months 3 and 6. N = 85 patients receiving biweekly intravenous pegloticase and 43 patients receiving placebo at baseline.

Khanna D, et al. Arthritis Care Res. 2012;64:1431-1446; Reinders MK, et al. Ther Clin Risk Manag. 2010;6:543-550; Sundy JS, et al. JAMA. 2011;306:711-720.

Urate-Lowering Therapy Emerging Options in Development • Lesinurad – Selective uric acid reabsorption inhibitor that inhibits URAT1 and OAT4 transporters in the renal tubule – Phase 3 data presented at 2014 ACR annual meeting • Arhalofenate – Dual-acting anti-inflammatory and urate-lowering therapy – Oral IL-1β inhibitor combined with uricosuric effects

IL = interleukin; OAT = organic anion transporter; URAT = uric acid transporter.

Edwards NL, So A. Rheum Dis Clin North Am. 2014;40:375-387; Fleischmann R, et al.

Rheumatology (Oxford). 2014;53:2167-2174; Saag KG, et al. Presented at: ACR Annual Meeting; November 2014; Boston, MA. Abstract L10.

Patients Achieving Serum Urate Levels <6.0 mg/dL at Month 6, %

Urate-Lowering Therapy Lesinurad + Allopurinol

80

Placebo + allopurinol Lesinurad 400 mg + allopurinol 54 a

60 40

28

Lesinurad 200 mg + allopurinol 67 a

59 a

55 a

23

20 0 CLEAR 1

CLEAR 2

Safety • • aP

Patients experiencing ≥1.5X increase in serum creatinine: placebo, 2.2%; lesinurad 200 mg, 5.9%; lesinurad 400 mg, 15.5%.

Most cases resolved without interrupting study medication

<.0001 vs placebo + allopurinol. N = 603 (CLEAR 1) and 610 (CLEAR 2).

CLEAR = Combining Lesinurad With Allopurinol in Inadequate Responders.

Saag KG, et al. Presented at: ACR Annual Meeting; November 2014; Boston, MA. Abstract L10.

Patients With â&#x2030;Ľ1 Gout Flare in Each 4-Week Period, %

Initiating Urate-Lowering Therapy Flare Risk Without Prophylactic Coverage 50

Febuxostat, 120 mg Febuxostat, 80 mg

40

Allopurinol, 300 mg

30 20 10 0 1-4

5-8

9-12 13-16 17-20 21-24 25-28 29-32 33-36 37-40 41-44 45-48 49-52

Period, Weeks

â&#x20AC;˘

Patients prescribed a prophylactic regimen from baseline to week 8

N = 762 patients with gout.

Becker MA, et al. N Engl J Med. 2005;353:2450-2461.

2012 ACR Gout Guidelines Gout Flare Prophylaxis Initiate with or just before initiating pharmacologic urate-lowering therapy • First-line: • Second-line:

Low-dose colchicine (0.5 or 0.6 mg once or twice daily) OR Low-dose NSAID (with proton-pump inhibitor where indicated) Low-dose prednisone or prednisolone (≤10 mg/d) Gout Signs/Symptoms

Evaluate gout symptoms with urate-lowering therapy

Continue pharmacologic prophylaxis No Gout Signs/Symptoms

Treat for the LONGEST Period Among the Following • At least 6 months • 3 months after achieving target serum urate level with no tophi • 6 months after achieving target serum urate level with ≥1 tophus

Khanna D, et al. Arthritis Care Res. 2012;64:1447-1461.

Gout Flare Prophylaxis With Colchicine Flare Prevention After Starting Allopurinol

Acute Gout Flares During the 6-Month Study, Mean

â&#x20AC;˘ Colchicine dose: 0.6 mg twice daily for ~6 months (many switched dose to 0.6 mg once daily) 3.5

Colchicine

3.0

Placebo

2.5 2.0 1.5 1.0

~65% fewer flares

~80% fewer flares

0.5 0.0 Baseline to Month 3 Early

Month 4 to 6 Late

N = 43 patients starting allopurinol for crystal-proven chronic gouty arthritis.

Borstad GC, et al. J Rheumatol. 2004;31:2429-2432.

Overall

2012 ACR Gout Guidelines Long-Term Management

Treat to target Serum urate level achieved?

NO

• Increase intensity of urate-lowering therapy • Re-evaluate serum urate

YES • Continue gout attack prophylaxis for ongoing gout symptoms and/or signs (≥1 tophus on physical exam) • Regularly monitor serum urate and assess for treatment adverse events • After palpable tophi and all acute and chronic symptoms have resolved, continue all measures (including pharmacologic urate-lowering therapy) to maintain serum urate at target indefinitely

Khanna D, et al. Arthritis Care Res. 2012;64:1431-1446.

Inadequate Outcomes for a “Curable” Disease

8.3 million patients with gout in US 4.5 million patients have an indication for uratelowering therapy

1.5 million patients have serum urate level <6.0 mg/dL

3.0 million patients have serum urate level ≥6.0 mg/dL

Poor treatment adherence

Treatment intolerance

Poor clinician performance

Edwards NL. Curr Rheumatol Rep. 2011;13:154-159; Juraschek SP, et al. Arthritis Care Res (Hoboken). 2015;67:588-592; Singh JA, et al. Curr Rheumatol Rep. 2013;15:307.

True treatment failure

Patients With Medication Possession Ratio ≥80%, %a

Comparing Drug Adherence Rates

80 60.8

60

40

51.2

68.4

65.4

72.3

54.6

36.8

20

0 Gout

aPercentage

Osteoporosis

Hypercholesterolemia

Seizure Disorders

T2DM

Hypothyroidism Hypertension

of days’ supply of required medications obtained by the patients over 1 year.

N = 706,032 adults with ≥1 of 7 medical conditions and incident use of medication for the condition.

Briesacher BA, et al. Pharmacotherapy. 2008;28:437-443.

Adherence to Urate-Lowering Therapy Improved Outcomes With a Nurse-Led Intervention Mean Serum Urate Level at Baseline, 7.7 mg/dL Intervention • Patient education • Individualized lifestyle advice • Slow upward titration of urate-lowering therapy – Usually allopurinol (median dose, 400 mg/d)

Serum urate goal not achieved

92% of patients met serum urate target of <6.0 mg/dL (85% achieved <5.0 mg/dL)

N = 106 patients with gout who completed intervention.

Rees F, et al. Ann Rheum Dis. 2013;72:826-830.

2012 ACR Gout Guidelines When to Refer • Unclear etiology for hyperuricemia • Refractory signs or symptoms of gout • Difficulty reaching urate targets – Especially with renal impairment or failed trials of xanthine oxidase inhibitors • Multiple and/or serious adverse events due to pharmacologic uratelowering therapy

Khanna D, et al. Arthritis Care Res. 2012;64:1431-1446.

Linkage of Long-Term Gout Management Goals Better Recognized

Good Patient Outcomes (Elimination of Acute Attacks, Reduction in Long-Term Urate Burden)

Diagnose, Treat, and Prevent Acute Gout Flares

Identify and Manage Comorbidities and Causes of Hyperuricemia

Treat to Target Serum Urate Level No Higher Than <6.0 mg/dL

Evidence-Based Multimodal Regimens, Patent Education, and Treatment Adherence Khanna D, et al. Arthritis Care Res. 2012;64:1431-1446.

PCE Action Plan  Aspirate the joint if presumptive diagnosis with ACR gout criteria is unclear, particularly if septic arthritis is possible  Use ultrasound or advanced imaging when examining patients with gout, particularly in early disease  Initiate pharmacologic urate-lowering therapy in all patients with tophi, multiple attacks/year, CKD stage 2 or higher, or previous urolithiasis  Prescribe prophylactic anti-inflammatory therapy for at least 6 months when initiating a pharmacologic urate-lowering regimen  Specifically assess patients with gout for adherence to prescribed regimens