Vol 16: Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout.Report as inadecuate



 Vol 16: Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout.


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This article is from Arthritis Research & Therapy, volume 16.AbstractIntroduction: The 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. Methods: Anti-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. Results: Sixty-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. Conclusions: Loss 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 registration: NCT00325195. Registered 10 May 2006, NCT01356498. Registered 27 October 2008.



Author: Lipsky, Peter E; Calabrese, Leonard H; Kavanaugh, Arthur; Sundy, John S; Wright, David; Wolfson, Marsha; Becker, Michael A

Source: https://archive.org/







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