Trial reportArthritis research & therapy2014
Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout.
Trial report in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 113 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized, Multicenter, Double-blind, Placebo-controlled Efficacy and Safety Study of 8 mg PEG-uricase in Two Dose Regimens in Hyperuricemic Subjects With Symptomatic Gout
Multicenter, Open Label Extension Study of 8 mg PEG-uricase in Subjects Who Completed Protocols C0405 or C0406 for Symptomatic Gout
Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 257 citations in OpenAlex.
- Uric acid lowering therapies for preventing or delaying the progression of chronic kidney disease.The Cochrane database of systematic reviews · 2017Pooled it
- Safety, Tolerability, and Efficacy of Shorter Infusion Durations of Pegloticase Administered to Patients With Uncontrolled Gout Receiving Methotrexate: AGILE Trial.Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases · 2026Trial
- A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings.Arthritis & rheumatology (Hoboken, N.J.) · 2023Trial
- Reducing Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate Mofetil in Patients With Refractory Gout: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- Outcome of pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma with hypersensitivity to pegaspargase treated with PEGylated Erwinia asparaginase, pegcrisantaspase: A report from the Children's Oncology Group.Pediatric blood & cancer · 2018Trial
- Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout.Arthritis research & therapy · 2017Trial
- Antibody-mediated recognition of chiral poly(2-oxazoline) nanorods driven by enantioselectivity.Chemical science · 2026Article
- Innovative Clinical Pharmacology, Modeling, and Simulation Strategies for Accelerating Rare Disease Drug Development.Journal of clinical pharmacology · 2026Review
- Antioxidant malic-acid-derived lipid nanoparticles delivering secretory uricase circRNA for hyperuricemia and complication management in mice.Nature communications · 2026Article
- The 100 top-cited articles in gout: A bibliometric analysis.Medicine · 2026Article
- Targeted Treatment for Hyperuricemia: The Drug Pipeline.Drugs & aging · 2026Review
- Therapeutic Strategies for Hyperuricemia: From Small-Molecule Inhibitors to RNA Therapeutics.ACS pharmacology & translational science · 2026Review
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- Pre-existing anti-polyethylene glycol antibodies in pregnant women and newborns.Journal of nanobiotechnology · 2026Observational
- Article
- Review
- Biological Therapies for Urate Lowering and Inflammation Control in Gout Management.Journal of inflammation research · 2026Review
- Article
- Single coadministration of erythrocyte-uricase conjugate and immunosuppressant induces durable immune tolerance for gout therapy.Science advances · 2025Article
- Considering the immunogenicity of PEG: strategies for overcoming issues with PEGylated nanomedicines.Nanomedicine (London, England) · 2025Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe efficacy of pegloticase, a polyethylene glycol (PEG)-conjugated mammalian recombinant uricase, approved for chronic refractory gout, can be limited by the development of antibodies (Ab). Analyses from 2 replicate, 6-month, randomized controlled trials were performed to characterize Ab responses to pegloticase.
methodsAnti-pegloticase, anti-PEG, and anti-uricase Ab were determined by validated enzyme-linked immunosorbent assays. Ab titers were analyzed for possible relationships with serum pegloticase concentrations, serum uric acid (sUA) lowering, and risk of infusion reactions (IRs).
resultsSixty-nine (41%) of 169 patients receiving pegloticase developed high titer anti-pegloticase Ab (> 1:2430) and 40% (67/169) developed anti-PEG Ab; 1 patient receiving placebo developed high titer anti-pegloticase Ab. Only 14% (24/169) of patients developed anti-uricase Ab, usually at low titer. In responders, patients showing sustained UA lowering, mean anti-pegloticase titers at week 25 (1:837 ± 1687 with biweekly and 1:2025 ± 4506 with monthly dosing) were markedly lower than in nonresponders (1:34,528 ± 42,228 and 1:89,658 ± 297,797, respectively). Nonresponder status was associated with reduced serum pegloticase concentrations. Baseline anti-pegloticase Ab, evident in 15% (31/212) of patients, did not predict subsequent loss of urate-lowering response. Loss of sUA response preceded IRs in 44 of 56 (79%) pegloticase-treated patients.
conclusionsLoss of responsiveness to pegloticase is associated with the development of high titer anti-pegloticase Ab that increase clearance of pegloticase and are associated with a loss of the sUA lowering effect and increased IR risk. Pre-infusion sUA can be used as a surrogate for the presence of deleterious anti-pegloticase Ab.
trial registrationNCT00325195. Registered 10 May 2006, NCT01356498. Registered 27 October 2008.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.