Gout

Question 1

Gout

Answer 1

• Disease spectrum including hyperuricemia and recurrent attacks of acute painful inflammatory arthritis
• Affects approximately 4% of adults
• “Disease of kings”

Question 2

Gout Risk Factors

Answer 2

• High purine diet (red meals, shellfish)
• Alcohol consumption
• Male
• Obesity
• Genetics
• Renal impairment

Question 3

Uric Acid Metabolism

Answer 3

• Byproduct of purine metabolism
• Waste product with no biological purpose
• Exclusively occurs in humans/primates which have a nonfunctional urate oxidase (uricase enzyme)

Question 4

Uricemia

Answer 4

• Overproduction (~10%) and underexcretion (~90%)
• Normal levels vary by gender
• Male: 3.4-7.0 mg/dL
• Female: 2.4-6.0 mg/dL
• Hyperuricemia: Uric acid >7 mg/dL (supersaturated)
• Higher uric acid levels = higher risk of gout
• May be an asymptomatic condition

Question 5

Clinical Presentation

Answer 5

• Rapid onset
• Excruciating pain
• Erythema
• Swelling
• Monoarticular vs polyarticular
• Tophus - deposits of urate crystals

Question 6

Joints Affected by Gout

Answer 6

• Generally 1st metatarsophalangeal joint is most affected (MTP) - big toe joint
• Typically affects small joints like insteps, ankles, wrists, fingers, elbows

Question 7

Diagnosis Considerations

Answer 7

• Symptoms
• History and risk factors
• Hyperuricemia
• Imaging and arthrocentesis

Question 8

Non-pharm Therapy

Answer 8

• Education: attacks are spontaneous and resolve in 3-10 days
• Lifestyle changes
• Joint rest: 1-2 days
• Topical therapy: apply ice

Question 9

Gout Lifestyle Changes

Answer 9

• Reduce purine rich food intake
• Reduce alcohol intake
• Increase water intake
• Weight loss

Question 10

Pharmacological Therapy - Treatment

Answer 10

• Terminate acute attack

- Initiate within 24 hours of symptoms onset

Question 11

Pharmacological Therapy - Prophylaxis

Answer 11

• Prevent recurrent attacks

- Should not be initiated during an acute attack

Question 12

Treatment Basics

Answer 12

• Monotherapy: mild to moderate pain on one major joint or a few small joints
• Dual Therapy: Severe pain with polyarticular or multiple large joints
• Concurrent prophylatic therapy should NOT be interrupted
• Educate about recurrent attacks and to self-initiate treatment based on symptoms

Question 13

Gout Treatment Agents

Answer 13

• NSAIDs
• Corticosteroids
• Colchicine

Question 14

NSAIDs

Answer 14

• Acceptable first line therapy
• Little evidence to support one agent over another
• Indomethacin is the most studied for gout - drug-of-choice for termination of acute attacks
• High-doses as early as possible for as short a duration as possible
• CAUTION: renal impairment, high-risk for GI bleed/ulceration, severe heart failure

Question 15

Common NSAID Regimens

Answer 15

• Indomethacin (Indocin) - 50 mg PO TID
• Naproxen (Naprosyn/Aleve) - 500 mg PO BID
• Sulindac - 200 mg PO BID

Initiate within 24-48 hours of symptoms onset and discontinue 2-3 days after resolution (usually 5-7 days total)

Question 16

Corticosteroids

Answer 16

• Acceptable first line therapy
• Similar efficacy to NSAIDs
• By mouth and intra-articular options

Question 17

Oral Corticosteroids Options

Answer 17

• Prednisone
• 0.5 mg/kgday PO for 5-10 days
• 30-60 mg/day PO until symptom improvement then taper over 7-10 days
• Methylprednisone dose oack is also an option

Question 18

Intra-articular Corticosteroid Options

Answer 18

• Methylprednisolone (Solu-Medrol) or Triamcinolone (Kenalog-10 or -40)
• DO NOT use if suspicion for infection/septic joints
• Usually limited to 1-2 joints, use IV/IM if multiple joints involved

Question 19

Colchicine

Answer 19

• Colcrys
• MoA: neutrophil inhibition resulting in reduced inflammation
• Acceptable first line if started within 36 hours of attack onset
• Can be used as a prophylatic at low doses (abortive at high doses)
• Many patients respond favorably bu
• Falling out of favor due to adverse reactions/toxicities

Question 20

Colchicine Dosing/Toxicities

Answer 20

• Traditional: 1.2 mg followed by 0.6 mg q2h until symptoms subside or GI distress occurs (Max of 4-6 mg/day)
• Colcrys dosing: 1.2 mg followed by 0.6 mg 1 hour later, then 0.6 mg TID until symptoms resolve
• Colcrys dosing has significantly less adverse GI effects
• Toxicities: nausea, vomiting, diarrhea, bone marrow suppression, hepatotoxicity
• Avoid in severe renal/hepatic impaired patients or those with blood dyscrasias

Question 21

Prophylaxis Basics

Answer 21

• May not be needed if first episode resolves quickly or if uric acid level minimally elevated
• Recommended if severe attacks occur, uric acid >10 mg/dL, or 2+ attacks per year
• Target uric acid level <6 mg/dL to lower attack frequency/complications
• Should monitor levels every few weeks initially during dose modification then every 6 months
• Initiate 1-2 weeks after acute attack resolution to prevent flare-ups and rebound attacks

Question 22

Prophylatic Agents

Answer 22

• Allopurinol
• Febuxostat
• Colchicine
• Probenecid
• Pegloticase
• Lesinurad

Question 23

Allopurinol

Answer 23

• Zyloprim
• MoA: XOI (Xanthine Oxidase Inhibitor) to reduce the production of uric acid
• Drug of choice for most patients
• Bridge with prophylatic colchicine or NSAID for acute attack precipitation
• Can continue during acute attacks

Question 24

Allopurinol Dosing

Answer 24

• Initial: 100 mg PO QD
• Titration: 100 mg increments every 204 weeks to achieve desired uric acid level
• Usual dose: 300 mg PO QD (max of 800 mg/day)
• Dose reduced in the renally dysfunctioned

Question 25

Allopurinol AE

Answer 25

- Mild: skin rash, N/V/D, headache - Severe allergic reactions - Highest risk of severe, possibly fatal, SE in the first few months

Question 26

Febuxostat

Answer 26

- Uloric - MoA: XOI that reduces production of uric acid - Non-inferior to allopurinol - Bridge with prophylatic colchicine or NSAID for acute attack precipitation - Can continue during acute attacks - Viable option in patients with allopurinol allergies, intolerance, or failures

Question 27

Febuxostat Dosing

Answer 27

- Initial: 40 mg PO QD - Titration: increase to 80 mg after 2 weeks to achieve desired uric acid level - Usual dose: 40-80 mg PO QD (max of 120/day) - IF CrCl < 30 mL/min then the max dosing is 40 mg PO QD

Question 28

Febuxostat AE

Answer 28

- Mild: skin rash, N/V/D, LFT elevation | - No allergic reactions

Question 29

Probenecid

Answer 29

- Benemid - MoA: uricosuric - inhibits tubular reabsorption of uric acid which increases its renal clearance - Alternative to XOI or additional agent in non-responders - Bridge with prophylatic colchicine or NSAID for acute attack precipitation - Can continue during acute attacks - Other indications: prolong PCN serum levels and neurosyphillis in addition to IM PCN (antibacterial action)

Question 30

Probenecid Dosing

Answer 30

- Initial: 250 mg BID x 7 days - Titration: increase in 500 mg increments every 4 weeks - Usual dose: 500-1000 mg PO BID (max of 2000 mg/day) - Avoid use in CrCl < 50 mL/min and history of renal stones

Question 31

Probenecid AE

Answer 31

-Mild: skin rash, N/V/D, kidney stones

Question 32

Pegloticase

Answer 32

- Krystexxa - MoA: PEGylated urate oxidase - Converts uric acid to allantoin - IV option used for severe debilitating, refractory gout - D/C PO anti-hyperuricemic agents prior to starting - Flare prophylaxis is with NSAIDs or colchicine is recommended starting at least 1 week prior to initiation - Dose: 8 mg IV q2w (expensive!!!)

Question 33

Pegloticase AE

Answer 33

- Infusion reactions - Allergic reactions - Gout flares **Premedicate with antihistamines and corticosteroids**

Question 34

Lesinurad

Answer 34

- Zurampic - DISCONTINUED - MoA: selective uric acid reabsorption inhibitor that blocks renal URAT1 transporter - Used in combination with XOI when goal uric acid levels not achieved with ZOI alone - XOI therapy is interrupted, lesinurad should be held - Dose: 200 mg PO QD in combination with XOI (also max dose) - CI with CrCl < 30 mL/min - AE: GERD, influenza, increased SCr, gout flares

Question 35

Other Gout Agents

Answer 35

- Fenofibrate | - Losartan

Question 36

Fenofibrate

Answer 36

- MoA: increases clearance of xanthine | - Potential add-on to XOI non-responders or patients with hyperlipidemia

Question 37

Losartan

Answer 37

- MoA: promotes renal excretion of uric acid | - Potential add-on to XOI nonresponders or patients with hyperlipidemia