Krystexxa (pegloticase) / Amgen - LARVOL DELTA

SHORTER INFUSION DURATION OF PEGLOTICASE COADMINISTERED WITH METHOTREXATE IN PATIENTS WITH UNCONTROLLED GOUT: SECONDARY AND EXPLORATORY ENDPOINTS OF THE AGILE TRIAL (EULAR 2025) - P4 | "With coadministration of MTX, shorter 60-min pegloticase infusions showed similar efficacy (response rates) and safety (IR, discontinuation) as MIRROR RCT. Additionally, patient-reported outcomes showed improvements consistent with prior pegloticase trials. Shorter infusion times will ease the logistical burden by receiving expeditious and efficient treatment for uncontrolled gout."

Clinical • Gout • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Rheumatology

Safety and Efficacy of Monthly Dosing of Pegloticase (Every 4 Weeks) With Methotrexate Co-administration in Patients With Uncontrolled Gout: Phase 4 FORWARD Open-label Trial (EULAR 2025) - P4 | "These data demonstrate the feasibility of Q4W increased-dose pegloticase while maintaining safety and efficacy comparable to pegloticase 8 mg Q2W in MIRROR RCT. PK analysis is underway to choose the appropriate dose for the phase 3 confirmatory trial."

Clinical • P4 data • Gout • Infectious Disease • Inflammatory Arthritis • Rheumatology

Oral Urate-Lowering Therapy Use and Efficacy Following Pegloticase Treatment: Findings from a Rheumatology Network Database. (PubMed, Rheumatol Ther) - "In this uncontrolled gout population, approximately two-thirds of patients began oral ULT within 30 days after their last pegloticase infusion. Those with longer pegloticase course more often had oral ULT efficacy, perhaps because of greater urate burden depletion, suggesting oral ULTs may be effective after successful pegloticase therapy. Further studies to understand any influence of urate burden on oral ULT efficacy are warranted."

Journal • Gout • Inflammatory Arthritis • Rheumatology

Monosodium Urate Crystal Depletion and Bone Erosion Response in Kidney Transplant Recipients With Uncontrolled Gout Treated With Pegloticase: PROTECT Serial Dual-Energy Computed Tomography Findings. (PubMed, Transplant Direct) - P4 | "However, unlike transplant-naive patients, subsequent bone erosion remodeling was not widely observed in urate-adjacent erosions, perhaps due to overall poor bone health in this patient population. ClinicalTrials.gov: NCT04087720."

Journal • Gout • Immunology • Inflammatory Arthritis • Novel Coronavirus Disease • Rheumatology • Transplantation

Disseminated Varicella-Zoster Virus in a Patient on Pegloticase and Mycophenolate Mofetil for Gout. (PubMed, Cureus) - "She was, therefore, started on acyclovir, and she clinically improved. In this case, our patient became profoundly immunosuppressed with the MMF-pegloticase regimen, which led to disseminated VZV. This case sheds light on the serious risks associated with this drug regimen."

Journal • Atrial Fibrillation • Cardiovascular • Dermatology • Diabetes • Gout • Herpes Zoster • Hypotension • Inflammatory Arthritis • Metabolic Disorders • Rheumatology • Type 2 Diabetes Mellitus • Varicella Zoster

Evaluation of Real-World Treatment Patterns and Healthcare Resource Utilization in Patients with Chronic Refractory Gout in the United States. (PubMed, Adv Ther) - "Despite the use of urate-lowering medications, patients with CRG had elevated serum urate levels and high HRU, underscoring the need for better treatment and management strategies for CRG to prevent gout flares and minimize long-term damage."

HEOR • Journal • Real-world evidence • Gout • Inflammatory Arthritis • Rheumatology

AMGEN REPORTS FIRST QUARTER 2025 FINANCIAL RESULTS (PRNewswire) - "TEPEZZA (teprotumumab-trbw) sales decreased 10% year-over-year to $381 million in the first quarter, primarily driven by 9% lower volume and 8% from a decrease in inventory levels, partially offset by higher net selling price; KRYSTEXXA (pegloticase) sales were flat year-over-year at $236 million in the first quarter, as 11% volume growth was offset by 10% from a decrease in inventory levels; UPLIZNA (inebilizumab-cdon) sales increased 14% year-over-year to $91 million in the first quarter, primarily driven by volume growth; TAVNEOS (avacopan) sales increased 76% year-over-year to $90 million in the first quarter, primarily driven by volume growth....TEZSPIRE (tezepelumab-ekko) sales increased 65% year-over-year to $285 million in the first quarter, driven by volume growth."

Sales • ANCA Vasculitis • Asthma • Gout • Immunology • Neuromyelitis Optica Spectrum Disorder • Ophthalmology • Thyroid Eye Disease

Corrigendum: Quality of life improvements and clinical assessments in kidney transplant recipients undergoing pegloticase treatment for uncontrolled gout: findings of the phase 4 PROTECT clinical trial. (PubMed, Front Immunol) - "[This corrects the article DOI: 10.3389/fimmu.2025.1516146.]."

HEOR • Journal • P4 data • Gout • Inflammatory Arthritis • Rheumatology • Transplantation

Quality of life improvements and clinical assessments in kidney transplant recipients undergoing pegloticase treatment for uncontrolled gout: findings of the phase 4 PROTECT clinical trial. (PubMed, Front Immunol) - "Given the high prevalence of uncontrolled gout in KT recipients, proper SU management is of particular importance. Additionally, intensive urate-lowering with pegloticase may have clinical and QOL benefits."

HEOR • Journal • P4 data • Gout • Immunology • Inflammatory Arthritis • Pain • Rheumatology • Transplantation

Innovative perspectives on uricase-based therapeutics for refractory gout (PubMed, Zhonghua Yi Xue Za Zhi) - "Currently approved uricase drugs include pegloticase and rasburicase. This article elaborates on the mechanism of uricase drugs in treating gout, the current status of pegloticas in managing refractory gout, the practical application of rasburicase in refractory gout cases, and the progress in research and clinical practices aimed at reducing anti-uricase antibodies. The aim of this article is to provide a reference for the rational use of uricase drugs in refractory gout and to enhance the therapeutic efficacy for this challenging condition."

Journal • Gout • Hematological Malignancies • Inflammatory Arthritis • Leukemia • Lymphoma • Oncology • Pediatrics • Rheumatology

Severe Tophaceous Polyarticular Gout: A Case Report and Review of Literature. (PubMed, Cureus) - "His management included colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and long-term urate-lowering therapy with allopurinol with a detailed plan for outpatient follow-up with a rheumatologist...The rising rates of hospitalizations for gout highlight significant gaps in current management practices, despite the availability of effective treatment options. This warrants an urgent need for healthcare providers to implement effective strategies that optimize outpatient care and enhance adherence to treatment protocols, ultimately improving patient outcomes and reducing healthcare burdens."

Journal • Genetic Disorders • Gout • Immunology • Inflammatory Arthritis • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Obesity • Orthopedics • Pain • Rheumatoid Arthritis • Rheumatology

Dual-energy CT bone erosion findings before and after pegloticase treatment in kidney transplant patients with uncontrolled gout: PROTECT trial (NKF-SCM 2025) - "Pegloticase induced near complete resolution of MSU deposits at Week 24. However, remodeling of MSU-adjacent erosions was not widely seen, perhaps due to underlying CKD-related demineralization."

Clinical • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Orthopedics • Rheumatology • Transplantation

A Trial to Investigate the Non-inferiority of Pegloticase Administered Every 4 Weeks (Q4W) With MTX Compared With Every 2 Weeks (Q2W) With MTX in Participants With Uncontrolled Refractory Gout (clinicaltrials.gov) - P4 | N=262 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Gout • Inflammatory Arthritis • Rheumatology

Disseminated Varicella-zoster Virus In a Patient on Pegloticase and Mycophenolate for Gout (AAAAI-WAO 2025) - No abstract available

Clinical • Gout • Herpes Zoster • Inflammatory Arthritis • Rheumatology • Varicella Zoster

Are participants in gout medication registration clinical trials representative of people with gout in the general population? (PubMed, Semin Arthritis Rheum) - "FDA approved gout medication trials since 2009 have not enrolled a study population that is representative of the US general population with gout, particularly regarding age, ethnicity, and cardiometabolic comorbidities. For broader applicability, future phase 3 trials should ensure the greater inclusion of women, older individuals, diverse ethnicities, and those with common gout-associated comorbid conditions."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Gout • Heart Failure • Hypertension • Inflammatory Arthritis • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Calculi • Renal Disease • Rheumatology

Rasburicase Plus Methotrexate Combination Therapy in a Case of Tophaceous, Difficult-to-Treat Gout. (PubMed, Cureus) - "The treatment of gout aims to reduce serum uric acid (sUA) levels by administering urate-lowering therapies (ULT) such as xanthine oxidase inhibitors (XOI: allopurinol, febuxostat) or uricosurics (e.g., benzbromarone)...Uricases such as pegloticase (PEG; polyethylene glycol-conjugated mammalian recombinant uricase), which degrades UA to allantoin (more soluble in urine), have emerged as a therapeutic alternative for such patients...However, as with PEG, it is occasionally associated with potentially serious infusion reactions. We present a preliminary report on the use of Rasburicase plus MTX combination therapy in treating a single case of refractory tophaceous gout, highlighting potential areas for further investigation."

Journal • Gout • Hematological Disorders • Hematological Malignancies • Inflammatory Arthritis • Oncology • Rheumatology

Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open-Label Trial. (PubMed, ACR Open Rheumatol) - "Pegloticase plus MTX response rate following failed monotherapy was lower (9% vs 71%) and IR rate was higher (18% vs 4%) than in pegloticase-naïve patients. These findings demonstrate the challenge of overcoming established antipegloticase antibodies and emphasize the importance of initiating immunomodulation before the first pegloticase exposure."

Journal • Monotherapy • Gout • Immunology • Inflammatory Arthritis • Metabolic Disorders • Rheumatology

Treatment-Emergent Major Adverse Cardiovascular and Thromboembolic Events were Infrequent During Clinical Trials of Pegloticase. (PubMed, Rheumatology (Oxford)) - P3, P4 | "CV/TE event incidence during pegloticase treatment was similar to the general gout population (31.7 events/1000 person-years). These findings suggest that pegloticase initiation does not put patients at a higher risk for CV/TE events."

Journal • Cardiovascular • Gout • Inflammatory Arthritis • Rheumatology

Quality of life and clinical gout assessments during pegloticase with and without methotrexate co-therapy: MIRROR randomized controlled trial exploratory findings. (PubMed, Rheumatol Adv Pract) - P4 | "However, patients receiving MTX co-therapy had greater benefits because of a higher sustained SU-lowering rate (60.0% vs. 30.8% in the PBO group at week 52). ClinicalTrials.gov, http://clinicaltrials.gov, NCT03994731."

HEOR • Journal • Gout • Immunology • Inflammatory Arthritis • Pain • Rheumatology

An update on the pharmacotherapy of gout. (PubMed, Expert Opin Pharmacother) - "Standard pharmacotherapies for gout flares include the options of colchicine, NSAIDs and oral or intramuscular corticosteroids, with IL-1 inhibitors newly established as an option for flare refractory to standard therapies...Initial treatments include allopurinol and febuxostat, with uricosuric agents, probenecid, sulfinpyrazone and benzbromarone, as adjuncts. There are also emerging therapies in development. However, there is increasing personalization of treatment, adjusting pharmacotherapy depending on comorbidities, such as chronic kidney disease and ischemic heart disease, as well as patient preference."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Coronary Artery Disease • Gout • Heart Failure • Immunology • Inflammatory Arthritis • Nephrology • Pain • Renal Disease • Rheumatology

Optimizing Gout Treatment: A Comprehensive Review of Current and Emerging Uricosurics. (PubMed, Joint Bone Spine) - "ULTs include xanthine oxidoreductase inhibitors, uricosurics, less commonly used in the US but widely used in Europe and Asia, including benzbromarone, dotinurad, and probenecid (the only US Food and Drug Administration (FDA) approved uricosuric in the US), and uricases, including rasburicase and pegloticase (available only in the US). Any drug that increases renal excretion of uric acid, independently of the mechanism through which it exerts its effect, may be considered a uricosuric drug. This review discusses drugs that increase renal excretion of uric acid, either approved or in development, as well as off-label drugs with uricosuric properties."

Journal • Review • Gout • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology

The Relationship Between Anti-drug Antibodies, Infusion Reactions, and Loss of Urate-lowering Response in Patients with Uncontrolled Gout Treated with Pegloticase (ACR Convergence 2024) - "Background/Purpose: Immunogenicity of pegloticase, a PEGylated uricase, can limit a sustained urate-lowering response and increase risk for infusion reactions (IRs).1 The MIRROR RCT trial demonstrated that methotrexate (MTX), when administered as co-therapy to pegloticase, increased treatment response rate (MTX vs. placebo [PBO] co-therapy: 71% vs. 39% during Month 6), decreased IR risk (4% vs. 31% thru Month 6), and decreased development of de novo anti-drug antibodies (ADAs; MTX vs. PBO: 23% vs. 50% thru Month 6; lower titers in MTX group).2 Here, we explored the relationship between ADAs and loss of SU-lowering response (LOR) and IR. Patients with uncontrolled gout (SU≥7 mg/dL, oral ULT inefficacy/intolerance and gout features [≥1 tophus, ≥2 flares/year, and/or gouty arthropathy) were administered up to 52 weeks of pegloticase (8 mg every 2 weeks; first infusion Day 1) with either oral MTX (15 mg/week) or PBO co-therapy (4-week MTX/PBO Run-in). These data further..."

Clinical • Gout • Inflammatory Arthritis • Rheumatology

Hepatic Fibrosis Before and During Intensive Urate-lowering with Pegloticase in the Presence and Absence of Methotrexate Co-therapy (ACR Convergence 2024) - P4 | "In agreement with prior data,5 sustained SU lowering with pegloticase showed Fib-4 stability through Wk 24 of therapy. In MIRROR RCT, stability persisted through Month 12 with and without MTX co-therapy. Importantly, 28.3% of patients had elevated Fib-4 at baseline; these subjects also had Fib-4 stability through Wk 52 of treatment."

Fibrosis • Gout • Hepatology • Immunology • Inflammatory Arthritis • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Rheumatology

Are Participants in Gout Clinical Trials Representative of People with Gout in the General Population? (ACR Convergence 2024) - "The approved gout medications were febuxostat, colchicine, pegloticase, lesinurad, and canakinumab. Clinical trials of gout medications approved by the FDA since 2009 have not enrolled a study population that is representative of the US population with gout, based on demographic features and cardiometabolic comorbidities. For broader applicability to the general population with gout, future phase 3 trials should ensure representative inclusion of women, older individuals, diverse ethnicities, and those with comorbid health conditions that are commonly experienced by people with gout."

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Gout • Heart Failure • Hypertension • Inflammatory Arthritis • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Calculi • Renal Disease • Rheumatology

A PEGylated Mammalian Uricase Suitable for Intramuscular Administration to Patients with Refractory Chronic Gout (ACR Convergence 2024) - "Background/Purpose: For patients with refractory chronic gout, i.e., those who have frequent gout flares and/or persistent tophi despite treatment with the highest tolerable doses of oral urate-lowering therapies, pegloticase is often prescribed... The Phase I clinical trial data indicated that PU5 is safe in healthy humans and has promising PK/PD and immunologic characteristics. More detailed information about PU5, including its amino acid sequence, preparation and characterization, pre-clinical PK/PD data, and Phase I clinical data, will be presented at the meeting."

Clinical • Gout • Inflammatory Arthritis • Rheumatology