KRYSTEXXALeah Smith

Duquesne University

PharmD Candidate Class of 2012

LEARNING OBJECTIVES

Gout prevalence and progressionCurrent medications and

indication for specific stages of gout

Krystexxa: how is it different, when is it indicated, and how much does it cost.

GOUT

Affects approximately 8.3 million people in the U.S.

Studies have associated an increased risk with obesity and hypertension.

More common in men than women Onset of symptoms is usually after the age

of 40.

http://www.gout.com

GOUT

Gout’s main characteristic is high levels of uric acid in the body (hyperuricemia) Uric acid is formed from the degradation of purines in

the body. When levels of uric acid reach 6.8mg/dl or higher

saturation occurs. When levels of uric acid get too high they form

crystals that deposit in joints causing pain, inflammation, and swelling

An enzyme called xanthine oxidase is the last step in converting purines to uric acid and is an important target for drug therapy.

http://www.gout.com

3 STAGES OF GOUT1. Asymptomatic hyperuricemia

Increased levels of uric acid start to build up in the body but are not at high enough levels for them to notice without blood work. Having asymptomatic hyperuricemia does not mean the individual will develop gout.

2. Acute gouty arthritis A one time quick onset flair of swelling redness,

tenderness, fever, etc after years of asymptomatic hyperuricemia

Lasts few days to several weeks, treated within 1 to 2 days, and usually involves a single joint.

Only way to definitely diagnose is through aspiration of the joint.

http://www.gout.com

3. Intercritical gout Attacks become longer and more frequent. If untreated patient will have second attack with 2 years After acute attack resolved patient needs evaluated for gout

and initiated on appropriate prophylactic and antihyperuricemic therapy

4. Tophaceous Gout Tophi form- inflammed deposits of crystals around a joint in

connective tissues and is disabling for the patients. Time from first attack to tophaceous gout is around 12

years. However, with prohpylactic antihyperuricemic treatment, only about 5% of patients develop into this stage. Patients who develop tophaceous gout even with

prophylaxis include: Excessive alcohol consumption Diuretic use Poor compliance Chronic kidney disease Organ transplant patients treated with cyclosporine Allergic to prophylaxis treatments

http://www.gout.com

http://www.gout.com/what-is-gout/signs-symptoms#/what-is-gout/effects

NONPHARMACOLOGIC RECOMMENDATIONS

Comorbid risk reduction Hypertension (losartan is preferred) Obesity Diabetes Hyperlipidemia (fenofibrate vs niacin)

Alcohol consumption Hydration Apply ice Diet

Reduction of protein intake (red meat, organ meat, green vegtables, shellfish)

http://www.gout.com

CURRENT TREATMENTS FOR GOUT

Based upon three main goals Prophylaxis

Initiate once attack has resolved (2-4 weeks), therapy is indefinate

Antiinflammatory For acute attacks

Antihyperuricmia For acute and prophylaxis

http://www.gout.com

MEDICATIONS (FOR ACUTE ATTACKS) NSAIDs

Indomethacin, Naproxen, Sulindac, Celecoxib, etc Used for short term therapy (used 3 to 4 days after resolution of

attack)

Colchicine Prevents the release of contents from neurtrophils (white blood cells)

causing inflammation while increasing the solubility of the crystals. Can be used as short term therapy during the initiation of long term

prophylaxis

Corticosteriods Only used if NSAID or colchicine contraindicated If one joint affected, prefer monoarticular intra-articular injections of

methylprednisolone or triamcinolone. If multiple joints, systemic prednisone can be used with taper.

ACTH, corticotropin Non-FDA approved Alternative to oral corticosteriods (given IM injections), only used if

everything else has been tried or contraindicated.

MEDICATIONS (PROPHYLAXIS) Antihyperuricemics

Probenecid- promotes renal clearance of uric acid, not effective in renally impaired patients (works in kidney)

Allopurinol- inhibits production of uric acid by inhibiting enzyme xanthine oxidase. Can cause hypersensitivity syndrome (common in patients with renal insufficiency using a diuretic)

Febuxostat (Uloric)- also inhibits xanthine oxidase, can be used in patients with hypersensitivity to allopurinol, higher risk of cardiovascular events, and is more costly.

NSAIDs Stages 1 or 2: Discontinue 6 months after the resolution

to normal levels Stage 3: Discontinue 6 months after resolution of tophi

lesion

http://www.gout.com

SECONDARY HYPERURICEMIA

Not gout but has gout like symptoms Is caused in patients that develop tumor lysis

syndrome These patients are typically those with leukemia,

lymphoma, or are being treated with chemotherapy

Elitek (Rasburicase) Only used for patients with TLS from lymphoma,

leukemia, or solid malignancy It is a urate oxidase enzyme that converts uric

acid to a more water soluble form. Only recommended as a one time only course.

http://www.gout.com

KRYSTEXXA (PEGLOTICASE) Pegloticase is an enzyme (same enzyme as

rasburicase) that selectively oxidizes uric acid to a water soluble form that allows for renal elimination. Difference is the addition of polyethylene glycol to the

enzyme causing a increase duration of action and a decrease in potential allergic reactions.

FDA approved for chronic gout refractory to conventional therapy. (approved 9/2010) Given 8mg via IV infusion over no less than 2 hours

every 2 weeks. Total treatment duration not established yet.

Reserved for patients that have contraindications to allopurinol or have failed to control uric acid levels <6mg/dl and have baseline uric acid levels of 8mg/dl or more.

Krystexxa. Micoromedex. 9.30.11Krystexxa. Clin Pharm. 9.30.11

KRYSTEXXA (PEGLOTICASE) Clinical Trials:

Three groups: Krystexxa 8mg every 2 weeks Krystexxa 8mg every 4 weeks Placebo

Looking for efficacy by determining patients with uric acid levels <6mg/dl at months 3 and 6.

Trial 1: 47% of patients in the every 2 week group kept uric acid levels <6mg/dl versus 20% in every 4 week group and 0% in placebo group.

Trial 2: 38% of patients in the every 2 week group kept uric acid levels <6mg/dl versus 49% in every 4 week group and 0% in placebo group. Even though the every 4 week group showed a similar level of

efficacy, this group experienced the largest number of anaphylaxis and infusion reactions and therefore is not recommended due to adverse events.

KRYSTEXXA (PEGLOTICASE) Administration is intravenous only through gravity

feed, syringe-type pump, or infusion pump. Patients are recommended premedication of

antihistamines and corticosteriods to prevent infusion reactions or anaphylaxis.

Patients are recommended to be treated with prophylaxis NSAIDs or colchicine one week prior and at least the next 6 months to prevent gout flairs unless contraindicated.

Patients must have this administered in a healthcare setting in order to monitor for infusion reactions or anaphylaxis. Can occur even after multiple infusions

Krystexxa. Micoromedex. 9.30.11Krystexxa. Clin Pharm. 9.30.11

KRYSTEXXA (PEGLOTICASE) Contains a Black Box warning for anaphylaxis and

infusion reactions. Patients should keep on schedule of every 2 weeks due to

increase risk of anaphylaxis and infusion reactions. Contraindications: G6PD blood disorder Precautions:

Gout flairs CHF: some patients in clinical trials with CHF experienced

exacerbations, keep up monitoring of CHF. No known drug interactions Uric acid levels should be evaluated before each

infusion. If two consecutive levels are >6mg/dl discontinuation of treatment may be needed. Anti-bodies against Krystexxa have been shown to form.

Krystexxa. Micoromedex. 9.30.11 Krystexxa. Clin Pharm. 9.30.11

COST

Comes in a 1ml vial (8mg/ml) AWP: $2,760/vial

Per month: $5,520 Yearly: $66,240

Need to consider other costs associated with treatment Anaphylaxis premedication Gout flair prophylaxis IV equipment Medical assistance

Medco. Manufacturer Pricing. Krystexxa. 9.30.11

SUMMARY Gout is a prevalent disease state in our

society The goal is to keep uric acid levels low and

prevent progression to chronic tophaceous gout.

However, once progressed, there are limitations on the therapy available

A direct enzyme oxidation of uric acid provides a unique alternative to conventional therapy failure.

Concerns: cost, possible adverse reactions, duration therapy remains effective.