Gout

Continued Managment of ULT

1. Titrate XOI to max dose. 2. Try Combo therapy. Add Uricosurice to XOI. Titrate both to max dose if needed. 3. Try Pegloticase. Measure serum urate every 2-5 weeks during titration and every 6 months once at goal.

Sulindac Dosing for Acute Gout Attack

200mg BID

IL-1 Inhibitors

Conditionally Recommended. Anakinra Canakinumab

ULT Management and Switching Therapies

Conditionally Recommended: Switch to different XOI if: Persistently high urate; Continued frequent flares (2+/yr); Unresovled SC Tophi

Indomethacin Dosing for Acute Gout Attack

50mg TID

Naproxen Dosing for Acute Gout Attack

750mg once, then 250mg Q8H

Pegloticase Dosing

8mg IV Q2 weeks. Must pre-treat w/ antihistamin and corticosteroid.

Inadequate Response

<20% improvement in pain score < 24 hours. <50% at 24+ Hours. If occurs, change to different monotherapy or start combo therapy. If that doesn't work, try a different combo or alternative therapies.

Gout

A spectrum of diseases including: Elevated serum urate (Uric acid) concentrations. Recurrent attacks of acute arthritis associated w/ monosodium urate crystals in synovial (joint) fluid leukocytes. Deposits of monosodium urate crystals in tissues and joints (tophi). Interstitial Kidney Disease. Uric Acid Nephroliathiasis (kidney stones)

Xanthine Oxidase Inhibitors

Allopurinol, Febuxostat

Probenecid

Alternative 1st line ULT. MoA: Inhibits Reabsorption of Uric Acid in Renal Proximal Tubule. Not recommended 1st line in Pts w/ CrCl < 50mL/min

Pegloticase ADR

Anaphylaxis, Infusion Reactions, Gout Flare, Bruising, Pruritus, Nausea. Contraindicated in G6PD Deficiency.

Combo Therapy for Gout.

Appropriate initial use if severe attack or if inadequate response to Monotherapy. Colchicine + NSAIDS Colchicine + Oral Corticosteroid IA Steroid w/ any Systemic Option

Extent of Acute Gout Attack.

Based on Number of Active Joints. One or a few small joints. 1 or 2 Large Joints (ankle, knee, wrist, elbow, hip shoulder). Polyarticular (4+ joints involving more than 1 region, or 3 separate Large Joints)

Severity of Gouty Arthritis Attack.

Based on Self Reported Pain (0-10 VAS). Mild: 4 or less. Moderate: 5-6. Severe: 7+

HLA-B*5801 Allele

Can be tested for in Pts of SE Asian descent and African Americans. Can be used to see if Pt is susceptible to Allopurinol Hypersensitivity Syndrome

Agents used for Prophylactic Therapy

Colchicine, NSAIDs, Prednisone

Pertinent Drug Interactions

Colchicine: CYP3A4 and PGP Inhibitors. Allopurinol and Febuxostat: Can icnrease concentration of Warfarin, Theophylline, Azathioprine. Probenecid: Uricosuric Effect diminished by low dose ASA. Inhibits: Penicillin, Cephalosporins, Rifampin, and Methotrexate.

Purines

Come from diet or are made in the body (De Novo synthesis or conversion of nucleic acids). These break down into nucleic acids or Uric Acid.

Non-Pharmacologic Therapy for Gout

Conditionally Recommended: Topical Ice.

Corticosteroid use in Acute Gout

If 1-2 large joints are affected, use IA. Otherwise use Oral, IA, IV, or IM

Fenofibrate MoA in Gout Treatment

Increased clearance of Hypoxanthine and Xanthine. No Acute Gout flare when initiated. Conditionally recommended Against unless otherwise indicated.

ULT is continued for how long?

Indefinitely

Colchicine MoA:

Inhibits Beta-tubulin polymerization into microtubules which interferes w/ cytoskeletal functions prevention activation and migration of Neutrophils

Losartan MoA in Gout Treatment

Inhibits Renal Tubular reabsorption of Uric Acid which increases urinary excretion and alkalinizes urine. Conditionally Recommended.

Febuxostat Dosing

Initial Dose: 40mg QD. Increase after 2 weeks if Uric Acid Goal not met. Max dose: 80mg QD.

Lifestyle management

Likely only to yield small changes in Uric Acid Concentrations, but may serve as triggers for flares. Recommended to limit intake of: Alcohol, Purines, HF Corn Syrup. Lose Weight if Overweight.

Additional Urate Lowering Agents

Losartan (not all ARBs). Fenofibrate.

Allopurinol ADR

Mild: Skin rash, Leukopenia, HA, Urticaria. Severe: Hypersensitivity Syndrome (Severe rash, Hepatitis, Nephritis, Eosinophilia). High Mortality.

Pegloticase

NEVER use 1st line. Reserved use in severe/refractory disease. MoA: Pegylated Recombinant Uricase converts uric acid to allantoin

What Combo can NOT be used

NSAIDs + Oral Corticosteroids due to GI Toxicity.

Dosing for Prophylactic Therapy

NSAIDs: Lowest Effective Dose. Colchicine: 0.6mg daily or 1-2x per day. Prednisone: <10mg QD. (2nd line)

NSAIDs for Gout

No Agent recommended over another. Use for 5-7 days or 48 hours after symptoms resolve. FDA Approved: Naproxen, Indomethacin, Sulindac

Herbal therapy

Not recommended. Consists of Cherries/Extract, Dairy Protein.

Clinical Presentation of Gout

Often Monoarticular. Most common affecting the Big Toe, but can also affect ankles, heels, knees, wrists, fingers, elbows.

Atypical Presentation of Gout

Often seen in elderly patients. Frequently confused w/ RA or OA.

Strongly Recommended to Start ULT

One or more SC Tophi Radiographic Damage attributable to Gout Frequent Flares (2+ per year)

Patient Specific Factors in Gout

Renal Insufficiency, GI Disease, Heart Failure, Hypertension, Polypharmacy, Financial Limitations

Colchicine Dosing

First line therapy if w/in 36 hours of onset. Acute Atttack: 1.2mg once then 0.6mg one hour later. Adjust Dose in Renal Impairment.

Colchicine ADR

GI (D/N/V), Myopathy, Myelosuppression. Interactions: Strong CYP3A4 Inhibitors, P-gp Inhibitors.

Probenecid Dosing

Initial: 250mg BID (Increase after one week). Maintenance: 500mg BID.

Signs/Symptoms of Gout

Joint Pain, Fever, Intense Pain, Erythema, Swelling, Warmth. Can also see increase in WBC (Leukocytosis). Can also see Uric acids in Fluid/Joints.

Allopurinol

First line ULT. Dosing: No more than 100/day initially. Use 50mg/day in Stage 3+ CKD. Doses over 300mg/day can be used but must be accompanied by education and monitoring.

Febuxostat ADR

Rash, liver Dysfunction, Nausea, Arthralgia, Allergic Reaction, Gout Flare. Use caution in severe Renal/Hepatic Impairment or if Pt had bad reaction to Allopurinol. BBW for Increased risk of death in PTS w/ CVS disease

IL-1 Inhibitors for Prophylaxis

Reserved use for Refractory causes.

IM Corticosteroid use.

Triamcinolone Acetonide 60mg then oral prednisone. There is a lack of consensus on using as Monotherapy.

Probenecid ADR

Urolithiasis, GI Upset, Rash, Allergic Reactions, Gout Flare. Prevent Urolithiasis w/ Fluids.

For Severe Pain or Polyarticular:

Use Combo Therapy.

For Mild to Moderate pain that is NOT Polyarticular

Use NSAIDs (no COX-2), Systemic Corticosteroids, or Colchicine.

Lifestyle change NOT Recommended

Vitamin C Supplementation

Urate Lowering Therapies

Xanthine Oxiase Inhibitors. Uricosuric Agents.

IA Corticosteroid use

Dose depends on Joint size (w/ or w/o oral treatment)

Medications Causing Gout

Diuretics (esp. Thiazides). Ethanol, Alcohol. Niacin, Nicotinic Acid. Salicylates.

Duration of Gout since Onset.

Early: < 12 Hours Well-Established: 12-36 Hours. Late: Over 36 Hours.

Risk Factors for Gout

Elevated Serum Urate. Older Age. Male. Lifestyle.

Not Recommended to Start ULT

First flare w/ no exceptions that indicate to start. Asymptomatic Hyperuricemia w/ no history of flares or tophi.

Etiology of Gout

Overproduction of Urate and/or Underexcretion of Uric Acid.

ULT NOT Recommended to switch to

Pegloticase for Pts who failed other ULT but have infrequent flares (<2/yr) AND no Tophi

Severe Gout Attack

Polarticular, Large Joints, Severe pain (7+)

Oral Corticosteroids for Gout

Prednisone 0.5mg/kg pe rday for 5-10 days then stop OR for 2-5 days at full dose then taper for 7-10 days then stop. Can also use a Medrol Pak.

Conditionally Recommended to Start ULT

Previously had a flare but infrequent (<2 per eyar). First Flare and CKD Stage. Uric Acid > 9mg/dL, or Urolithiasis

Uricosuric Agents

Probenecid, Pegloticase

General Principles of Acute Gout Management

Should be treated w/ Pharmacologic Therapy. Optima Care should be initiated w/in 24 hours of onset. Ongoing Pharmacologic ULT should not be interrupted during acute attack. Use Colchicine if it has been less than 36 hours since onset. No COX-2 Inhibitors.

Prophylactic Therapy for Gout

Strongly Recommended. Administer concomitantly w/ ULT. Continue for 3-6 months.

Pharmacologic Therapy for Gout

Strongly Recommended: Low dose Colchicine, NSAIDs, Corticosteroids. Conditionally Recommended: IL-1 Inhibitors (Only if prior therapies fail).