Specialty Pharmacy Management of Gout

New drugs and drugs in the pipeline for gout have changed the treatment for this painful disease, one of the oldest documented diseases. Here's an update on what's new and what specialty pharmacists need to know as they counsel patients for gout.

The specialty pharmacy industry has expanded in recent years, not only due to new drugs being approved in therapeutic categories historically viewed as specialty drugs—such as oral oncology and hepatitis C—and expanded indications of currently approved medications, but also due to new biologic drug approvals in therapeutic categories that have historically been treated solely with traditional oral small molecule therapy. The 2010 FDA approval of Savient Pharmaceuticals’ Krystexxa (pegloticase injection) to treat gout has moved this disease to the list of inflammatory conditions that are treated with a biologic therapy and have entered the realm of specialty pharmacy management.

OVERVIEW OF GOUT¹

Gout is one of the oldest documented diseases and consists of recurrent episodes of pain and joint inflammation caused by the formation of monosodium urate monohydrate crystals within the joint space and soft tissue. These crystal deposits, called “tophi,” can lead to joint damage and renal impairment. Gout is related to underexcretion or overproduction of uric acid. Ninety percent of patients with gout have high uric acid levels, and although it is thought that the level of uric acid itself does not cause gout, acute changes in uric acid levels do precipitate gout flares.

Gout typically presents as spontaneous onset of pain, swelling, and inflammation of a joint. Inflammation of the proximal joint of the big toe, called “podagra,” is involved in the initial presentation of gout in 50% of cases and is eventually involved in up to 90% of all gout cases. However, podagra can also be caused by other etiologies, and psoriatic arthritis, reactive arthritis, and sarcoidosis should be ruled out.

Gout can also manifest in the ankle, wrist, and knee. Initial gout attacks consist of a rapid onset of redness, swelling, and hypersensitivity that, if untreated, resolve in less than 2 weeks. Acute gout flares can result from a sudden increase or decrease in serum uric acid. Increases in serum uric acid can result from overconsumption of beer or liquor and foods high in purine, while decreases in serum uric acid can be seen with the use of medications that lower the levels of serum uric acid. If gout remains untreated, attacks can target many joints at once, occur more frequently, and last longer. Untreated gout may develop symptoms of chronic arthritis affecting multiple joints that can resemble rheumatoid arthritis.

TREATMENT OF GOUT^1-3

Treatment of an acute gout attack is the first step in managing gout. Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually used as first-line therapy in patients who do not have contraindications to them. Indomethacin is commonly used, but other NSAIDs can be useful as well. NSAIDs should be continued until gout symptoms have resolved for at least 2 days.

Colchicine, once a mainstay of treatment for acute gout, is now considered a second-line option due to its narrow therapeutic index and risk of side effects. If colchicine is used, it should be started within 24 hours of the beginning of the attack to be effective. Oral steroids or intra-articular injectable steroids can also be used for management of acute gout attacks.

Once the acute gout attack is under control and the patient has been free of gout flares for several weeks, the focus shifts to managing chronic gout. The goals of long-term chronic gout treatment are to lower serum uric acid levels to 6 mg/dL or less as well as focus on lifestyle changes that reduce dietary purine intake in order to prevent additional gout flares.

Allopurinol, Uloric (febuxostat), or probenecid can be used to lower serum uric acid levels based on individual patient characteristics. Because these agents lower serum uric acid, the regimen should also include colchicine or low-dose NSAID treatment to reduce the risk of gout flares during the time the serum uric acid level is decreasing. Since 2010, Krystexxa (pegloticase injection) has also been available as a treatment option for those adult patients who are refractory to conventional serum acid-lowering agents. Krystexxa is administered as an 8-mg IV infusion every 2 weeks.

GOUT PIPELINE^4-11

Arcalyst (rilonacept) is an IL-1 inhibitor already approved in the United States for Cryopyrin-Associated Periodic Syndromes (CAPS). The phase III trials of rilonacept were designed to study prevention of gout flares when given in conjunction with allopurinol rather than reduction of pain in acute flares. In the PRE-SURGE 1 phase III study, patients who received 80 mg of rilonacept saw a 73% reduction in flares compared with placebo and patients who received 160 mg of rilonacept saw an 80% reduction in flares compared with placebo. The PRE-SURGE 2 trial showed a 72% reduction of flares per patient for both patients treated with rilonacept 80 mg and rilonacept 160 mg compared with placebo. Regeneron also conducted a phase III safety study, entitled RE-SURGE, in which treatment-emergent adverse events were generally well balanced between those taking the study drug and those on placebo. Injection site reactions were more prevalent with the treatment group than with placebo (15.2% vs 3.3%) but were generally considered mild. Regeneron has announced that the FDA has accepted Arcalyst’s supplemental biologics license application (BLA) for review and that the target FDA action date is July 30, 2012.

Ilaris (canakinumab), already approved in the United States for Cryopyrin-Associated Periodic Syndromes (CAPS), was also being considered for use in acute gout flares. It is a fully humanized monoclonal antibody that provides selective inhibition of IL-1 beta. Novartis filed for FDA approval in the first half of 2011. In June 2011, an FDA advisory committee voted 11 to 1 against recommending approval of Ilaris for treating attacks of gout and voted unanimously against approval of Ilaris for delaying and reducing the frequency of future attacks due to the risk of serious infections seen in the study drug compared with placebo. In August 2011, Novartis received a complete response letter from the FDA indicating that additional clinical data to evaluate the benefit-risk profile in refractory patients would be needed prior to reconsideration for approval.

SPECIALTY PHARMACY CONSIDERATIONS FOR GOUT MANAGEMENT

• Counsel patients on potential side effects, therapy considerations, and potential drug/drug interactions of medications used in acute gout attacks.
• Educate patients on potential side effects, therapy considerations, and potential drug/drug interactions of medications used to lower serum uric acid in chronic gout patients and the importance of recognizing that an increased risk of flare is present with any change in serum uric acid levels; hence, the importance of prophylaxis while concomitantly taking the serum uric acid— lowering agent.
• Review patient’s profile for drugs that may increase serum uric acid, such as thiazide diuretics.
• Assess barriers in adherence and persistency of chronic gout therapy.
• Provide tools to remove identified barriers to adherence and persistency, such as copayment assistance resources, refill management, and reminder strategies for the patient.
• Become familiar with the process and required elements for Uloric and Krystexxa prior authorizations, if necessary. Manufacturer reimbursement resources may also be of assistance and can be found on the respective product Web sites.
• Krystexxa management considerations include monitoring of serum uric acid prior to each infusion and premedication with antihistamines and corticosteroids.
• Patients of African or Mediterranean ancestry who may be at higher risk for Glucose-6-phosphate dehydrogenase (G6PD) deficiency should be screened prior to administration of Krystexxa due to the risk of hemolysis and methemoglobinemia.
• Monitor serum uric acid levels prior to infusions and consider discontinuing Krystexxa treatment if levels increase to above 6 mg/dL after initially decreasing, particularly when 2 consecutive levels above 6 mg/dL are observed, as the risk of infusion reactions is higher in patients who have lost therapeutic response.
• Clinical data collection elements for a specialty pharmacy gout management program could include serum uric acid levels, number and date of flares, joints affected, number and location of tophi, and medications previously tried. SPT If gout remains untreated, attacks can target many joints at once, occur more frequently, and last longer.

The above information is a selective summary of publicly available information and is accurate as of the date of writing. Please consult the sources for complete reference information. The views expressed in this article are those of the author alone and not of Managed Health Care Associates, Inc. Any patient care, treatment, dosing, or other decisions related to the subject matter of this article should be based on an independent evaluation of the patient’s condition and medical history by his/her treating physician.

References:

1. Rothschild B. Gout and pseudogout treatment and management. Medscape Reference website. http://emedicine.medscape.com/article/329958-overview. Published December 13, 2011. Accessed December 14, 2011.

2. FDA approves Krystexxa (pegloticase) for the treatment of chronic gout refractory to conventional therapy. Savient Pharmaceuticals website. http://investor.savient.com/releasedetail.cfm?ReleaseID=507578. Published September 14, 2010. Accessed December 14, 2011.

3. Krystexxa prescribing information. Savient Pharmaceuticals website. http://krystexxa.com/pdfs/KRYSTEXXA_Prescribing_Information.pdf. Published September 2010. Accessed December 14, 2011.

4. Clinical Trials.gov website. www.clinicaltrials.gov. Accessed June 18 and 19, 2011.

5. BSR: canakinumab tames gout flares. MedPage Today website. www.medpagetoday.com/MeetingCoverage/BSR/25996. Published April 18, 2011. Accessed June 18, 2011.

6. Novartis drug gives pain relief in gouty arthritis. Reuters website. www.reuters.com/article/2011/05/25/us-novartis-arthritis-idUSTRE74O59220110525. Published May 25, 2011. Accessed June 18, 2011.

7. Novartis says experimental drug quells gout attacks, pain. Bloomberg website. www.bloomberg.com/news/2011-05-25/novartis-says-experimental-drug-quells-gout-attacks-pain.html. Published May 25, 2011. Accessed June 18, 2011.

8. Novartis data shows ACZ885 for severe gouty arthritis provided better pain relief and reduced risk of new attacks. Fierce Biotech website. www.fiercebiotech.com/press-releases/novartis-data-shows-acz885-severe-gouty-arthritis-provided-better-pain-reli. Published May 25, 2011. Accessed June 18, 2011.

9. Greer J. FDA denies biologic for gout. MedPage Today website. www.medpagetoday.com/Rheumatology/GeneralRheumatology/28262. Published August 29, 2011. Accessed December 14, 2011.

10. Arcalyst (rilonacept) meets primary and all secondary endpoints in second phase 3 trial for prevention of gout flares in patients initiating uric acid-lowering therapy. Regeneron website. http://newsroom.regeneron.com/releasedetail.cfm?ReleaseID=553068. Published February 28, 2011. Accessed June 18, 2011.

11. Regeneron announces FDA acceptance of Arcalyst (rilonacept) supplemental biologics license application for review. Regeneron website. http://newsroom.regeneron.com/releasedetail.cfm?ReleaseID=626006. Published November 22, 2011. Accessed December 14, 2011.

Stacey Ness, PharmD, has worked in both national specialty pharmacy and payer organizations and has experience in clinical management, adherence and persistency programs, and chronic disease cost optimization strategies. Dr. Ness is active in the Consortium of Multiple Sclerosis Centers, Academy of Managed Care Pharmacy, National Home Infusion Association, and Hematology and Oncology Pharmacy Association, and has served on the Minnesota Medicaid Drug Formulary Committee since 2008. She is currently associate director of specialty services at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey.