Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout
Abstract Background 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 (N...
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13075-017-1396-8 |
| _version_ | 1819226774879338496 |
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| author | Leonard H. Calabrese Arthur Kavanaugh Anthony E. Yeo Peter E. Lipsky |
| author_facet | Leonard H. Calabrese Arthur Kavanaugh Anthony E. Yeo Peter E. Lipsky |
| author_sort | Leonard H. Calabrese |
| collection | DOAJ |
| description | Abstract Background 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. Methods IRs 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. Results There 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. Conclusion IRs 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. |
| first_indexed | 2024-12-23T10:30:50Z |
| format | Article |
| id | doaj.art-12fbbd89ed2c4e2bb37c4cd8fbfc0dee |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-23T10:30:50Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-12fbbd89ed2c4e2bb37c4cd8fbfc0dee2022-12-21T17:50:26ZengBMCArthritis Research & Therapy1478-63622017-08-011911710.1186/s13075-017-1396-8Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory goutLeonard H. Calabrese0Arthur Kavanaugh1Anthony E. Yeo2Peter E. Lipsky3Cleveland Clinic, Department of Rheumatic & Immunologic DiseasesUniversity of California San Diego, Division of Rheumatology, Allergy and ImmunologyHorizon PharmaAMPEL BioSolutions, LLCAbstract Background 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. Methods IRs 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. Results There 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. Conclusion IRs 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.http://link.springer.com/article/10.1186/s13075-017-1396-8AnaphylaxisGoutHypersensitivityPegloticase |
| spellingShingle | Leonard H. Calabrese Arthur Kavanaugh Anthony E. Yeo Peter E. Lipsky Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout Arthritis Research & Therapy Anaphylaxis Gout Hypersensitivity Pegloticase |
| title | Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout |
| title_full | Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout |
| title_fullStr | Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout |
| title_full_unstemmed | Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout |
| title_short | Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout |
| title_sort | frequency distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout |
| topic | Anaphylaxis Gout Hypersensitivity Pegloticase |
| url | http://link.springer.com/article/10.1186/s13075-017-1396-8 |
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