Krystexxa (pegloticase) / Amgen - LARVOL DELTA

Recapturing Immune Tolerance to Pegloticase for the Management of Tophaceous Gout (clinicaltrials.gov) - P1 | N=2 | Completed | Sponsor: University of California, Los Angeles | Enrolling by invitation ➔ Completed | Trial completion date: Feb 2027 ➔ Nov 2024 | Trial primary completion date: Feb 2026 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

Pegloticase for Tumor Lysis Syndrome (KIDNEY WEEK 2025) - "In our analysis of 398 cases of TLS at UTMD Anderson Cancer Center in 2018, we found that almost 60% (240 cases) needed repeated doses of rasburicase, often up to 3 doses several days apart to bring the serum uric acid down to 6.0 and help with recovery of acute kidney injury (AKI). Conclusion Pegloticase is extremely effective and safe in cancer patients with severe tumor lysis syndrome. Uric acid levels were less than 1 for 14 days after a single dose and stayed below 3.5 for 30 days."

Acute Kidney Injury • Nephrology • Oncology • Renal Disease

Meaningful Clinical Improvement in Serum Uric Acid (sUA) Levels with Concomitant Use of Low-Dosage Mycophenolate Mofetil (MMF) and Pegloticase in Patients with CKD and Uncontrolled Gout (KIDNEY WEEK 2025) - P2 | "Conclusion This small, retrospective study evaluating a lower daily dose of MMF ≤500mg BID concomitantly with pegloticase led to rapid sUA reduction, clinical improvement in gout symptoms, with both low AEs and discontinuation rate. Kidney function showed stability in most patients with both less severe and more severe stages of CKD."

Clinical • Cardiovascular • Chronic Kidney Disease • Coronary Artery Disease • Diabetes • Diabetic Nephropathy • Gout • Hypertension • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Peripheral Arterial Disease • Renal Disease • Rheumatology

Kidney Safety Findings in Patients with Uncontrolled Gout Treated with Pegloticase with and Without Methotrexate (KIDNEY WEEK 2025) - "Mild hematological AEs (Grade 1 leukopenia and Grade 2 anemia) occurred in 1 pt in the MTX group (none in PBO group). Conclusion MTX safety data from MIRROR RCT indicate that low-dose MTX was generally well tolerated among uncontrolled gout pts with no observed adverse impact on renal function."

Clinical • Anemia • Chronic Kidney Disease • Dermatology • Gastrointestinal Disorder • Gout • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Renal Disease • Rheumatology

Management of Uncontrolled Gout Among Nephrology Professionals: Findings from a Medical Chart Audit (KIDNEY WEEK 2025) - "ULTs most recently administered were allopurinol (60%), febuxostat (35%), colchicine (18%) and pegloticase (7%). Conclusion Despite available ULTs, patients with UG and CKD still have high sUA levels and experience gout-related symptoms which negatively impact their quality of life. These findings highlight the existing burden in patients with UG and CKD as well as a need for treatment optimization and new therapies."

Cardiovascular • Chronic Kidney Disease • Diabetes • Genetic Disorders • Gout • Hypertension • Inflammatory Arthritis • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Obesity • Orthopedics • Renal Disease • Rheumatology

Patient and Caregiver Perspectives on the Burden of Disease in Uncontrolled Gout: A Cross-Sectional Survey Study (ACR Convergence 2025) - "Patients were currently using the following ULT treatments: allopurinol (49%), pegloticase (26%), febuxostat (20%), and probenecid (4%). This is the first study to present data on caregiver burden associated with UG, highlighting significant challenges and reduced HRQOL for caregivers and patients with UG. Both reported HRQOL below the general US population with the largest impact in physical health-related domains, likely due to clinical manifestations of UG for patients, and for caregivers, the physical demands of caring for a patient. Employed individuals also experienced notable work impairment demonstrating the multifaceted impacts of UG."

Clinical • HEOR • Gout • Inflammatory Arthritis • Rheumatology

Management of Uncontrolled Gout Among Rheumatologists: Findings from a Medical Chart Audit (ACR Convergence 2025) - "Other patients most recently received febuxostat (24%), colchicine (18%) and pegloticase (4%). This study highlights the challenges rheumatologists face in managing UG and unmet needs in gout treatments as evidenced by high sUA levels, frequent flares and tophi presence and low adherence rates to current ULTs."

Cardiovascular • Genetic Disorders • Gout • Hypertension • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Obesity • Orthopedics • Renal Disease • Rheumatology

Racial Differences in Real-World Use of Urate-Lowering and Adjunctive Therapies for Gout: A 10-Year Propensity-Matched Cohort Study (ACR Convergence 2025) - "Outcomes captured 1–10 y post-index were initiation of allopurinol, febuxostat, pegloticase, colchicine, oral corticosteroids, NSAIDs, IL-1 inhibitors, arthrocentesis, most-recent SU, and composite MACE (myocardial infarction, heart failure, stroke). Despite similar comorbidity profiles, minority adults with gout were less likely to initiate guideline-preferred allopurinol yet more likely to receive febuxostat and multiple acute agents, had higher residual SU, and experienced greater cardiovascular morbidity than non-Hispanic-White adults. These findings highlight treatment and outcome inequities and call for targeted dose-titration protocols, SU monitoring, and cardiovascular-risk mitigation strategies to improve gout care in underserved populations."

Clinical • Real-world • Real-world evidence • Cardiovascular • Congestive Heart Failure • Gout • Heart Failure • Inflammatory Arthritis • Myocardial Infarction • Rheumatology

Tolerance of Methotrexate Coadministered with Pegloticase in Patients with Uncontrolled Gout: Findings from MIRROR RCT (ACR Convergence 2025) - "MTX safety data from MIRROR RCT demonstrates that MTX in uncontrolled gout pts does not lead to an increased number/frequency of TEAEs vs PBO, including no increase in durable liver function changes and no increase in infections. These findings further underscore the safety of MTX coadministration with pegloticase during the 12 month MIRROR RCT."

Clinical • Anemia • Cardiovascular • Dental Disorders • Dermatology • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Gout • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Stomatitis

Pharmacokinetics of Ready-to-Use Pegloticase Formulation Compared to Standard Pegloticase Dosing: Data from the AGILE Study (ACR Convergence 2025) - "Background/Purpose: Pegloticase is approved for uncontrolled gout as 8-mg infusions admixed in 250 cc of normal saline over 120 minutes or more administered every 2 wks with methotrexate (MTX) coadministration. Pegloticase given in RTU form of premixed 50 cc with 8 mg of pegloticase coadministered with MTX over 60 minutes showed comparable safety, efficacy, and PK results to standard pegloticase. Among a small number of patients that switched from standard pegloticase to RTU formulation, no change in PK was seen."

PK/PD data • Gout • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Rheumatology

Evaluating Patient Outcomes Pre and Post Pegloticase Initiation among Uncontrolled Gout Patients: Findings from MORE2 Registry and Medicare Fee-For-Service Claims Data (ACR Convergence 2025) - "However, real-world data on its effectiveness, particularly with methotrexate co-treatment, remains limited...The primary outcome, gout flare, was identified as follows: 1) having an inpatient visit with a primary diagnosis of gout or 2) having an outpatient or emergency department claim with a diagnosis of gout accompanied by treatment or follow-up visit within a 7-day period, or 3) an outpatient or ED claim with a diagnosis for unspecified joint pain accompanied by a claim for oral/injectable colchicine within 7 days... Pts with CRG, treated with pegloticase in the MORE2 and Medicare FFS, showed a substantial reduction in the rate of gout flares during the follow-up periods. These data further support the use of pegloticase, as a uric acid debulker, for CRG management, thus decreasing the risk of flareup."

Clinical • Medicare • Reimbursement • US reimbursement • Cardiovascular • Chronic Kidney Disease • Diabetes • Gout • Hypertension • Immunology • Inflammatory Arthritis • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Osteoarthritis • Renal Disease • Rheumatology • Type 2 Diabetes Mellitus

Co-Use of Mycophenolate Mofetil with Pegloticase Yielded Similar Clinical Outcomes as the Co-Use of Methotrexate (ACR Convergence 2025) - "49% of pegloticase patients were treated with immunomodulating co-therapy, among which MMF was 33% of IMM use, with most patients going on MMF having advanced CKD. Pegloticase duration, effectiveness in terms of sUA reduction and eGFR stability in the MMF group were similar to the MTX group. The co-therapy of MMF and pegloticase may be an option for patients with pre-existing renal impairment."

Clinical • Clinical data • Chronic Kidney Disease • Gout • Immunology • Inflammatory Arthritis • Renal Disease • Rheumatology

Efficacy of Pozdeutinurad (AR882) in Treatment Naïve and Suboptimally Treated Gouty Arthritis with Tophi (ACR Convergence 2025) - "To date, only intravenous (IV) therapies such as pegloticase is indicated in urate-lowering (ULT) refractory patients and has demonstrated tophi dissolution by caliper measurement and Dual Energy Computer Tomography (DECT). Pozdeutinurad 75 mg monotherapy or in combination with allopurinol in tophaceous patients refractory and naïve to ULT were effective in sUA lowering, demonstrating high rates of complete resolution of target tophus and reduction in urate crystal burden. Pozdeutinurad alone or combination may provide an effective treatment option for patients with chronic tophi and inadequate response to their current treatment regimens."

Clinical • Gout • Immunology • Inflammatory Arthritis • Rheumatology

The Care Pathway and Treatment Patterns in Patients with Uncontrolled Gout: A Real-World Survey of Physicians In The United States (ACR Convergence 2025) - "The most common ULT was allopurinol (63%), followed by febuxostat (29%) and pegloticase (13%). To our knowledge, this is the first real-world study examining the care pathway and treatment patterns of patients with UG. These data highlight that patients with UG experience extended periods of time with elevated sUA and UG clinical manifestations, despite receiving ULT for almost two years. Given that efficacy was noted as the most common reason for treatment choice and area of improvement, there is a need for optimal treatment utilization and alternative options for patients with UG."

Clinical • Real-world • Real-world evidence • Gout • Inflammatory Arthritis • Rheumatology

Safety, Tolerability, and Efficacy of Shorter Infusion Durations of Pegloticase Administered to Patients With Uncontrolled Gout Receiving Methotrexate: AGILE Trial. (PubMed, J Clin Rheumatol) - P4 | "Safety, tolerability, and efficacy results of pegloticase infused for 60 minutes were comparable to traditional infusion durations (120 min), making shorter infusion times feasible."

Journal • Gout • Inflammatory Arthritis • Rheumatology

Microbial uricase enzymes in hyperuricemia management: Sources, challenges, and technological advances. (PubMed, J Microbiol Methods) - "Recombinant uricases, such as rasburicase and pegloticase, have emerged as therapeutic interventions, effectively mitigating the severity of gout. The application of uricase-based nanosensors, chips, biosensors, and nanocomposites for facile uric acid detection in samples is also highlighted. Given its considerable potential, uricase stands as a promising tool in the clinical realm for treating gouty and hyperuricemic conditions."

Journal • Review • Gout • Inflammatory Arthritis • Oncology • Rheumatology

A Patient Presenting with Joint Deformities and ST-Elevation Myocardial Infarction. (PubMed, Diagnostics (Basel)) - "Following a Heart Team consultation, the patient was bridged with cangrelor and underwent urgent hybrid coronary artery bypass grafting and left atrial appendage occlusion. Despite standard therapies, this patient experienced continued disease progression, prompting referral for advanced treatment with pegloticase and canakinumab. Multidisciplinary care and personalized strategies are essential in managing severe, refractory gout with multi-organ involvement."

Journal • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Gout • Heart Failure • Hypertension • Inflammatory Arthritis • Myocardial Infarction • Nephrology • Rheumatology

Updates in uricase therapy for gout. (PubMed, Curr Opin Rheumatol) - "Exogenous uricases available and those under development are discussed, focusing on immunomodulation and anti-inflammatory prophylaxis to reduce flares, prevent antidrug antibody formation and infusion reactions, and mitigate loss of efficacy in patients with uncontrolled gout needing uricase replacement therapy."

Journal • Developmental Disorders • Gout • Immunology • Inflammatory Arthritis • Oncology • Rheumatology

Gout Remission With Pegloticase-Induced Intensive Urate-Lowering Therapy: A Post Hoc Clinical Trial Analysis. (PubMed, ACR Open Rheumatol) - P4 | "Using the study full and simplified definitions, nearly half to three-quarters of patients who remained on pegloticase for 52 weeks achieved gout remission. This novel analysis provides evidence that remission is possible in many patients with uncontrolled gout within one year of intensive, sustained urate-lowering."

Journal • Retrospective data • Gout • Immunology • Inflammatory Arthritis • Pain • Rheumatology

Dual-Energy CT Bone Erosion Findings Before and After Pegloticase Treatment in Kidney Transplant Patients with Uncontrolled Gout: PROTECT Trial (WTC 2025) - "DECT revealed poor bone health in KTRs with uncontrolled gout, likely due to CKD and mineral bone disease mechanisms. 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 chronic kidney disease-related demineralization."

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

Infectious Complications in a Patient Receiving Immunomodulatory Therapy for Gout. (PubMed, Cureus) - "We present the case of a 75-year-old female patient with multiple comorbidities, including diabetes and chronic kidney disease, who developed a significant gluteal abscess that progressed to pelvic osteomyelitis and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia while undergoing treatment for refractory gout with pegloticase (Krystexxa) and mycophenolate mofetil (CellCept). The patient has recovered from the infection; however, a 2.5 × 1.5 × 7.3 cm wound persists. The wound has remained clean with healthy granulation tissue and no exposed bone or signs of an active infection. This case highlights the importance of assessing infection risk in patients receiving immunomodulatory treatments for gout and demonstrates the need for close monitoring and multidisciplinary care, particularly in those with underlying comorbidities."

Journal • Chronic Kidney Disease • Diabetes • Gout • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Renal Disease • Rheumatology

Gout Management in Patients With CKD. (PubMed, Am J Kidney Dis) - "While limitations or exclusions of some treatment options are warranted, others that are traditionally followed, such as the doses used for urate lowering therapies like allopurinol or febuxostat, may lead to undertreatment of gout...While there is a potential role of sodium/glucose cotransporter 2 inhibitors in lowering serum urate, it is limited in chronic kidney disease. Lastly, the use of immunomodulators to improve outcomes for pegloticase, a pegylated form of uricase, show promise for increasing the utility of pegloticase in cases where it is warranted."

Journal • Review • Chronic Kidney Disease • Gout • Immunology • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology • Transplantation • HLA-B

Assessment of drug induced hyperuricemia and gout risk using the FDA adverse event reporting system. (PubMed, Sci Rep) - "Among the hyperuricemia-related reports, telaprevir was the most frequently implicated drug, whereas lenalidomide ranked highest in the gout-related reports...Specifically, peginterferon alfa-2b was found to be an independent risk factor for drug-induced hyperuricemia, while 20 drugs-including pegloticase, febuxostat, allopurinol, rofecoxib, and furosemide-were identified as independent risk factors for drug-induced gout...Furthermore, key independent risk factors-including sex, age, and specific drugs-were identified through machine learning and multivariate analysis. These findings provide valuable insights for pharmacovigilance and clinical medication management."

Adverse events • Journal • Gout • Inflammatory Arthritis • Rheumatology

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