Abstract
BackgroundTo assess frequency and distribution of infusion reactions (IRs) in responders and nonresponders in randomized clinical trials (RCTs) of intravenous pegloticase and the utility of the National Institute of Allergy and Infectious Disease/Food and Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for identifying anaphylaxis in subjects experiencing IRs.MethodsIRs from two RCTs of pegloticase were evaluated and categorized as anaphylaxis, hypersensitivity, or other. Serum levels of tryptase and total hemolytic complement (CH50) were evaluated at the time of all IRs. Frequency of IRs by each category was evaluated in all subjects, responders or nonresponders to pegloticase.ResultsThere were 113 IRs in 1695 infusions. Of the 113 IRs, 6 met criteria for anaphylaxis, 53 had one feature of anaphylaxis and were designated as “hypersensitivity”, and 54 had no features and were designated “other”. In subjects receiving pegloticase every 2 weeks (Q2w), a total of 852 infusions were administered and the IR frequency was 0.5% in responders and 9.7% in nonresponders. In subjects receiving pegloticase every 4 weeks (Q4w), a total of 846 infusions were given and the IR frequency was 2.6% in responders and 12.2% in nonresponders. There were no differences among the three categories of IRs with regard to clinical course or biochemical evidence of immune activation determined by CH50 or tryptase levels.ConclusionIRs mostly occurred in nonresponders. NIAID/FAAN criteria for anaphylaxis did not identify pegloticase-related IRs as having a higher frequency of immune activation or a more severe course. The results are consistent with the conclusion that discontinuance of pegloticase if uric acid rises to >6 mg/dL will decrease the frequency of IRs.
Highlights
To assess frequency and distribution of infusion reactions (IRs) in responders and nonresponders in randomized clinical trials (RCTs) of intravenous pegloticase and the utility of the National Institute of Allergy and Infectious Disease/Food and Allergy and Anaphylaxis Network (NIAID/Food Allergy and Anaphylaxis Network (FAAN)) criteria for identifying anaphylaxis in subjects experiencing Infusion reaction (IR)
Results from the primary publication of the two pivotal clinical trials for pegloticase indicated that IRs occurred in 25.9% of patients treated with pegloticase biweekly, 40.5% of those treated with pegloticase monthly, and 4.6% of those who received placebo
Since the development of nonresponder status largely reflected the development of anti-drug antibodies, the results suggest that antipegloticase antibodies contribute to the tendency to develop IRs
Summary
To assess frequency and distribution of infusion reactions (IRs) in responders and nonresponders in randomized clinical trials (RCTs) of intravenous pegloticase and the utility of the National Institute of Allergy and Infectious Disease/Food and Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for identifying anaphylaxis in subjects experiencing IRs. The uricolytic pegloticase is a mammalian recombinant uricase conjugated to monomethoxypoly (ethylene glycol) [1]. A post-hoc analysis carried out by the United States Food and Drug Administration (FDA) identified 14 cases of “anaphylaxis” or potential anaphylaxis among the 273 patients tested in the phase 2 and 3 clinical development programs for pegloticase [4]. An additional analysis using the National Institute of Allergy and Infectious Disease (NIAID)/Food Allergy and Anaphylaxis Network (FAAN) criteria for anaphylaxis [6] indicated that 3 of 85 patients treated with pegloticase every 2 weeks (Q2w) had IRs meeting these criteria [4].
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