This was the case with 45-year-old Khash B. from Orange County, California. First diagnosed with gout at age 21, Khash had been living with this painful condition for 20 years before he found the help he needed. What started as reoccurring discomfort in his foot soon became frequent and severe pain that eventually spread to his knees and even elbows. For Khash, it was debilitating. “When you’re feeling a gout flare-up and you’re just lying in bed in the morning—you almost have to work up mentally that as soon as you put your feet on the ground, you’re going to be dealing with pain.” While some people can manage gout with daily oral medications, others experience a chronic form of the condition with painful symptoms that do not respond to traditional treatments. This is often referred to as ‘out-of-control chronic gout’ which is classified by persistently high serum uric acid levels, intense joint pain, lingering discomfort, swelling, redness, and limited range of motion in their joints.4,5 Khash was having recurrent gout attacks that were not well controlled and for him, every day was a struggle. He was unable to make plans with family and friends in fear of having a gout flare-up. At his worst, Khash experienced a flare every week, with little time off from pain. As Khash puts it, “I knew the pain was coming and I knew it would only get worse.” While Khash tried oral medications and making diet and lifestyle changes, he wasn’t experiencing any relief. Something had to change. In the summer of 2019, Khash was referred to a rheumatologist, Dr. Orrin Troum, who listened to his gout story and was able to make the appropriate recommendation that would eventually change the course of his disease. Khash was having recurrent gout attacks, and he had formed tophi from the abundance of uric acid in his body. These painful, bulbous growths needed to be addressed, as did his uric acid levels, to target the root cause of Khash’s gout. That’s why Dr. Troum recommended Khash begin a treatment called KRYSTEXXA® (pegloticase), a prescription medicine used in adults to help reduce the signs and symptoms of gout that are not controlled by other treatments. KRYSTEXXA is not recommended if you have high levels of uric acid without a history of gout. KRYSTEXXA is an infusion (IV) treatment for adults that helps reduce uric acid crystal buildup by providing the enzyme the body needs to convert uric acid into allantoin. Unlike uric acid, allantoin is water-soluble and flows easily out of the kidneys. As a result, uric acid levels are able to reach the zone where the crystals can dissolve. KRYSTEXXA also prevents new uric acid crystal buildup, so people with the condition can have fewer flares and take control of their chronic gout. Patients should always consult with their physicians before starting a new medication. Do not receive KRYSTEXXA if you have a rare blood problem called glucose 6-phosphate dehydrogenase (G6PD) deficiency or favism. Serious allergic reactions may happen in some patients who receive KRYSTEXXA. These allergic reactions can be life threatening and usually happen within 2 hours of the infusion. KRYSTEXXA should be given to you by a doctor or nurse in a healthcare setting where serious allergic reactions can be treated. Your doctor or nurse should watch for any sign of allergic reaction during and after treatment with KRYSTEXXA. Common side effects of KRYSTEXXA include gout flare-ups, allergic reactions, nausea, bruising, sore throat, constipation, chest pain, and vomiting. Please read additional Important Safety Information, including Boxed Warning, at the end of this article. Khash underwent IV treatment every other week. After his first infusion, he experienced an increase in gout flares, which his doctor assured him was expected. After a few additional infusions, he started seeing a difference in his number of flare-ups. After six months of treatment with KRYSTEXXA, Khash’s uric acid levels had drastically decreased. Individual results may vary. Gout flares may increase when starting KRYSTEXXA, particularly in the first three months of treatment. Do not stop receiving KRYSTEXXA even if you have a flare. In clinical studies, gout flares decreased after 3 months of treatment. Your doctor may give you other medicines to help reduce your gout flares after starting KRYSTEXXA.6 Today, Khash is counting his blessings. “There’s finally a light at the end of the tunnel,” says Khash. His wife is just as grateful, exclaiming, “He’s finally back to the Khash I met 11 years ago.” He revels in being able to lead a more active lifestyle and the ability to plan important moments with his family. To hear more stories like Khash’s visit www.KRYSTEXXA.com Patients should always consult with their physicians before starting a new medication. Common side effects of KRYSTEXXA include gout flare-ups and allergic reactions. Patients should watch for any sign of allergic reaction during and after treatment with KRYSTEXXA. Please see below for Important Safety Information. KRYSTEXXA is a prescription medicine used in adults to help reduce the signs and symptoms of gout that are not controlled by other treatments. IMPORTANT SAFETY INFORMATION What is the most important information I should know about KRYSTEXXA (pegloticase)? Serious allergic reactions may happen in some patients who receive KRYSTEXXA. These allergic reactions can be life threatening and usually happen within 2 hours of the infusion. KRYSTEXXA should be given to you by a doctor or nurse in a healthcare setting where serious allergic reactions can be treated. Your doctor or nurse should watch you for any signs of a serious allergic reaction during and after your treatment with KRYSTEXXA. Tell your doctor or nurse right away if you have any of these symptoms during or after your treatment with KRYSTEXXA:

Wheezing, shortness of breath, cough, chest tightness, chest pain or trouble breathingDizziness, fainting, fast or weak heartbeat or feeling nervousReddening of the face, itching, hives, rash or feeling warmSwelling of the throat or tongue, throat tightness, hoarse voice or trouble swallowing

Who should not receive KRYSTEXXA? Do not receive KRYSTEXXA if you have a rare blood problem called glucose 6-phosphate dehydrogenase (G6PD) deficiency or favism. Your doctor should test you for G6PD before you start KRYSTEXXA. KRYSTEXXA is not recommended if you have high levels of uric acid without a history of gout. Before you receive KRYSTEXXA, tell your doctor if you:

Know you have G6PD deficiencyEver had any heart problems or high blood pressureAre pregnant or planning to become pregnant. It is not known if KRYSTEXXA will harm your unborn babyAre breastfeeding or plan to breastfeed. It is not known if KRYSTEXXA passes into your breast milk

Tell your doctor about all the medicines you take. Do not take any other uric acid lowering drug, such as allopurinol or febuxostat (Uloric®), while taking KRYSTEXXA. Prior to your treatment with KRYSTEXXA, your doctor may give you medicine to help reduce your chance of getting a reaction. Take these medicines as directed by your doctor or nurse. Your doctor will also test your uric acid levels prior to each treatment to monitor your response to KRYSTEXXA. What are the possible side effects of KRYSTEXXA? Please review important information section above. The most common side effects in patients taking KRYSTEXXA were gout flare-ups or attacks, allergic reactions, nausea, bruising, sore throat, constipation, chest pain and vomiting. This is not a complete list of all possible side effects. Tell your doctor or treatment team if you have any side effect that bothers you or that does not go away. Please see the Medication Guide and Prescribing Information for more information. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/safety/medwatch, or call the FDA at 1-800-FDA-1088. +++ References:1. Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK. Arthritis Rheumatol. 2019 Jun;71(6):991-999. 2. Schett G, Schauer C, Hoffmann M, Herrmann M. RMD Open. 2015;1(Suppl 1):e000046. 3. Doghramji PP, Wortmann RL. Postgrad Med. 2012;124(6):98-109. 4. Francis-Sedlak M, LaMoreaux B, Padnick-Silver L, Holt RJ, Bello AE. Rheumatol Ther. 2020;10.1007/s40744-020-00260-1. 5. Brook RA, Forsythe A, Smeeding JE, Lawrence Edwards N. Curr Med Res Opin. 2010 Dec;26(12):2813-21. 6. KRYSTEXXA (pegloticase) [prescribing information] Horizon. KRYSTEXXA is a trademark owned by or licensed to Horizon. ©2021 Horizon Therapeutics plc P-KRY-01723 02/21 P-KRY-01723

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