Pharmacists Can Stay Aware of the Evolving Landscape of Gout Treatment to Address Unmet Needs

Gout, a common and multifaceted form of arthritis, causes abrupt attacks of pain, swelling, redness, and tenderness in 1 or more joints. The inflammatory disease is more common in men than in women and typically develops in middle-aged individuals. Although it is less frequent, young adults and children could also be affected by gout and present more severe symptoms.^1,2

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High levels of uric acid surrounding joints and other tissues in the body causes gout, most often in the big toe, ankles, knees, elbows, wrists, and fingers. Intense and sudden gout flares typically strike at night, causing severe pain within the first 4 to 12 hours, but discomfort could last for a few days to a few weeks. However, individuals with serum urate (SU) levels above 6 mg/dL can experience multiple flares per year that last longer and increase nodular masses of uric acid crystals, or tophi. As more attacks occur, the joints are unable to move and function properly, especially if left untreated.^1-3

Risk factors such as diet, weight, medical conditions, certain medications, family history of gout, age, sex, and recent surgery or trauma can increase levels of uric acid in the body. An overproduction of uric acid causes inflammation and swelling and does not allow the acid to dissolve in the blood, pass through the kidneys, and flow into the urine.¹

The Current Treatment Landscape

Currently, urate-lowering therapy (ULT), anti-inflammatory drugs, and nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat gout and manage acute gout flares.⁴

ULTs

ULT, such as allopurinol or febuxostat, is a cornerstone in the long-term management of gout. These medications work by reducing the production of uric acid or increasing its excretion, ultimately lowering serum urate levels and preventing the formation of painful urate crystals in the joints.

While ULT is effective, it prevents challenges such as the need for lifelong adherence, the potential for initial gout flare-ups when starting treatment, and the requirement for regular monitoring of uric acid levels. Additionally, some patients may experience adverse effects.

• Allopurinol (Zyloprim; Casper Pharma LLC) is a xanthine oxidase inhibitor indicated to treat gout. It works by reducing the production of uric acid in the body. The medication is administered in tablet form and is recommended for once or twice daily use; however, it could take several months before reducing gout flares.⁵
• Febuxostat (Uloric; Takeda Pharmaceuticals) is used for gout treatment among individuals who did not respond well to allopurinol. This xanthine oxidase inhibitor is also available in tablet form, indicated for daily use among adults and pediatric patients.⁶
• Pegloticase (Krystexxa; Savient Pharmaceuticals) is an intravenous (IV) infusion used to convert uric acid into allantoin, which is a chemical compound that is easily removed by the body. This IV infusion is reserved for individuals who did not tolerate previous gout therapies.⁷
• Anakinra (Kineret; Sobi & Boehringer Ingelheim) and canakinumab (Ilaris; Novartis Pharmaceuticals) are both IL-1 inhibitors that are given by injection when other medications are not effective.⁷

Anti-Inflammatory Medications

Anti-inflammatory medications play a crucial role in managing gout by reducing pain and inflammation during acute attacks. These medications have various mechanisms to alleviate symptoms and improve joint function. Pharmacists should emphasize the importance of taking these medications exactly as prescribed and check patients' records for possible drug-drug interactions.

• Corticosteroid could control gout inflammation and pain. They can be taken orally or administered via injection.⁷
• Colchicine (Mitigare; Hikma) is indicated to treat acute attacks of gout and prevent further flares.⁷

NSAIDs

Although NSAIDs are commonly used to treat gout flares, they pose challenges due to gastrointestinal adverse effects, especially with long-term use, and may not be suitable for individuals with certain health conditions, such as kidney disease or heart problems.

• Ibuprofen and naproxen sodium are OTC NSAIDs that could treat gout and prevent further attacks.¹
• Indomethacin (Indocin; Tivorbex) and celecoxib (Celebrex; Pfizer) are prescription NSAIDs, providing a more powerful treatment option.¹

Despite the use of these available therapies, the inability to maintain SU levels below 6 mg/dL remains a significant challenge._³

Developing Treatments

SEL-212 (Sobi), a novel investigational combination medicine for the treatment of chronic refractory gout (CRG), could provide further treatment options. SEL-212 is designed to reduce SU levels and harmful tissue urate deposits, which can lead to unbearable gout flares and joint deformity if left untreated.³

The innovative biologic therapy contains SEL-037 (Pegadricase; Selecta Biosciences), co-administered with immune tolerance technology, and is designed to limit the formation of antidrug antibodies (ADAs). The development of ADAs is a result of unwanted immune responses to biologic medications, diminishing their effectiveness and causing adverse effects—a persistent challenge across various treatment methods and conditions, including gout.³

Unlike traditional urate-lowering therapies that focus on reducing uric acid production or increasing its excretion, SEL-212 utilizes a different mechanism. It employs a PEGylated uricase enzyme to break down existing uric acid in the body, potentially offering a more direct and potent way to lower urate levels. This approach could be particularly beneficial for patients who are intolerant or unresponsive to current therapies or those who have difficulty achieving target urate levels. Furthermore, its potential for less frequent dosing compared to some existing treatments could improve patient adherence and overall outcomes.

SEL-212 was granted FDA fast track designation in March 2024, and the company recently announced the submission of a rolling biologics license application (BLA), based on positive results from the phase 3 DISSOLVE 1/2 study. Individuals treated with SEL-212 demonstrated a significant response rate when treated with a 0.15 mg/kg monthly dose.³

If granted FDA approval, SEL-212 could change the paradigm of gout treatment, offering a new and effective treatment option for individuals that suffer from chronic refractory gout.³

REFERENCES

1. Gout. Mayo Clinic. News release. Published November 16, 2022. Accessed February 5, 2025. https://www.mayoclinic.org/diseases-conditions/gout/symptoms-causes/syc-20372897

2. Gout. NIH Arthritis and Musculoskeletal and Skin Diseases. News release. Published December 2023. Accessed February 6, 2025. https://www.niams.nih.gov/health-topics/gout#:~:text=Who%20Gets%20Gout?,tends%20to%20be%20more%20severe

3. Ferruggia K. SEL-212 Shows Promise in Treating Chronic Refractory Gout with High Response Rates. Pharmacy Times. News release. Published January 22, 2025. Accessed February 6, 2025. https://www.pharmacytimes.com/view/sel-212-shows-promise-in-treating-chronic-refractory-gout-with-high-response-rates

4. The landscape of pathophysiology guided therapeutic strategies for gout treatment. NIH. News release. Published January 5, 2024. Accessed February 6, 2025. https://pubmed.ncbi.nlm.nih.gov/38037803/#:~:text=Abstract,line%20strategies%20for%20gout%20treatment

5. Allopurinol. MedlinePlus. Updated September 15, 2023. Accessed February 6, 2025. https://medlineplus.gov/druginfo/meds/a682673.html#:~:text=Allopurinol%20is%20used%20to%20treat,in%20one%20or%20more%20joints)

6. Febuxostat (oral route). Mayo Clinic. News release. Updated February 1, 2025. Accessed February 6, 2025. https://www.mayoclinic.org/drugs-supplements/febuxostat-oral-route/description/drg-20074780#cmp-body

7. Treatments for Gout. Arthritis Foundation. News release. Published June 10, 2022. Accessed February 6, 2025. https://www.arthritis.org/health-wellness/treatment/treatment-plan/disease-management/treatments-for-gout