Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study
Abstract Background There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of patients with aHUS treated with eculizumab. Methods Patients with aHUS...
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | BMC Nephrology |
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| Online Access: | http://link.springer.com/article/10.1186/s12882-019-1314-1 |
| _version_ | 1818015066089324544 |
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| author | Jan Menne Yahsou Delmas Fadi Fakhouri Christoph Licht Åsa Lommelé Enrico E. Minetti François Provôt Eric Rondeau Neil S. Sheerin Jimmy Wang Laurent E. Weekers Larry A. Greenbaum |
| author_facet | Jan Menne Yahsou Delmas Fadi Fakhouri Christoph Licht Åsa Lommelé Enrico E. Minetti François Provôt Eric Rondeau Neil S. Sheerin Jimmy Wang Laurent E. Weekers Larry A. Greenbaum |
| author_sort | Jan Menne |
| collection | DOAJ |
| description | Abstract Background There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of patients with aHUS treated with eculizumab. Methods Patients with aHUS who participated in any of five parent eculizumab trials and received at least one eculizumab infusion were eligible for enrollment in a long-term follow-up study. Rates of thrombotic microangiopathy (TMA) manifestations off versus on eculizumab were evaluated. Additional endpoints included change from baseline estimated glomerular filtration rate (eGFR), long-term renal outcomes, and serious targeted treatment-emergent adverse events. Results Among 93 patients (0–80 years of age), 51 (55%) remained on eculizumab and 42 (45%) discontinued; for those who discontinued, 21 (50%) reinitiated therapy. Patients who reinitiated eculizumab had similar baseline clinical characteristics to patients who remained on eculizumab, with higher likelihood of genetic/autoimmune complement abnormalities, more prior TMAs, and longer disease course versus those who did not reinitiate. Mean eGFR improved rapidly and remained stable for up to 6 years on eculizumab. In patients who discontinued, there was a trend toward decreasing renal function over time from discontinuation. Additionally, off-treatment TMA manifestation rates were higher in those aged < 18 years at diagnosis, with identified genetic/autoimmune complement abnormalities, or history of multiple TMAs prior to eculizumab initiation. The safety profile was consistent with previous studies. Three definite and one possible meningococcal infections related to eculizumab were reported and resolved with treatment. Three deaths unrelated to eculizumab were reported. Conclusions The current study confirms the efficacy and safety of eculizumab in aHUS, particularly with regard to long-term renal function and TMA events. Pediatric age at disease onset and presence of genetic or autoimmune complement abnormalities are risk factors for TMA events off treatment. Overall, patients who discontinue eculizumab may be at risk for additional TMA manifestations and renal function decreases. Discontinuation of eculizumab, with careful monitoring, is an option in select patients with consideration of patient preference, organ function normalization, and risk factors for relapse, including mutational analysis, age of onset, and history of multiple TMA episodes. Trial registration ClinicalTrials.gov NCT01522170, January 31, 2012. |
| first_indexed | 2024-04-14T06:52:23Z |
| format | Article |
| id | doaj.art-643443cd37ae4a068ce31cb8a246610a |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-04-14T06:52:23Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
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| series | BMC Nephrology |
| spelling | doaj.art-643443cd37ae4a068ce31cb8a246610a2022-12-22T02:06:59ZengBMCBMC Nephrology1471-23692019-04-0120111210.1186/s12882-019-1314-1Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational studyJan Menne0Yahsou Delmas1Fadi Fakhouri2Christoph Licht3Åsa Lommelé4Enrico E. Minetti5François Provôt6Eric Rondeau7Neil S. Sheerin8Jimmy Wang9Laurent E. Weekers10Larry A. Greenbaum11Department of Nephrology and Hypertension, Klinik für Nieren- und HochdruckerkrankungenService de Néphrologie Transplantation Dialyse, CHU de BordeauxDepartment of Nephrology and Immunology, UMR 643, CHU de NantesDivision of Nephrology, The Hospital for Sick Children, 555 University AvenueAlexion Pharma GmbHDepartment of Nephrology, Niguarda HospitalDepartment of Nephrology, CHU de LilleUrgences Néphrologiques et Transplantation Rénale, Hôpital TenonInstitute of Cellular Medicine, University of Newcastle upon TyneAlexion Pharmaceuticals, Inc.Néphrologie-Transplantation, CHU de LiègeDivision of Pediatric Nephrology, Emory University School of Medicine and Children’s Healthcare of AtlantaAbstract Background There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of patients with aHUS treated with eculizumab. Methods Patients with aHUS who participated in any of five parent eculizumab trials and received at least one eculizumab infusion were eligible for enrollment in a long-term follow-up study. Rates of thrombotic microangiopathy (TMA) manifestations off versus on eculizumab were evaluated. Additional endpoints included change from baseline estimated glomerular filtration rate (eGFR), long-term renal outcomes, and serious targeted treatment-emergent adverse events. Results Among 93 patients (0–80 years of age), 51 (55%) remained on eculizumab and 42 (45%) discontinued; for those who discontinued, 21 (50%) reinitiated therapy. Patients who reinitiated eculizumab had similar baseline clinical characteristics to patients who remained on eculizumab, with higher likelihood of genetic/autoimmune complement abnormalities, more prior TMAs, and longer disease course versus those who did not reinitiate. Mean eGFR improved rapidly and remained stable for up to 6 years on eculizumab. In patients who discontinued, there was a trend toward decreasing renal function over time from discontinuation. Additionally, off-treatment TMA manifestation rates were higher in those aged < 18 years at diagnosis, with identified genetic/autoimmune complement abnormalities, or history of multiple TMAs prior to eculizumab initiation. The safety profile was consistent with previous studies. Three definite and one possible meningococcal infections related to eculizumab were reported and resolved with treatment. Three deaths unrelated to eculizumab were reported. Conclusions The current study confirms the efficacy and safety of eculizumab in aHUS, particularly with regard to long-term renal function and TMA events. Pediatric age at disease onset and presence of genetic or autoimmune complement abnormalities are risk factors for TMA events off treatment. Overall, patients who discontinue eculizumab may be at risk for additional TMA manifestations and renal function decreases. Discontinuation of eculizumab, with careful monitoring, is an option in select patients with consideration of patient preference, organ function normalization, and risk factors for relapse, including mutational analysis, age of onset, and history of multiple TMA episodes. Trial registration ClinicalTrials.gov NCT01522170, January 31, 2012.http://link.springer.com/article/10.1186/s12882-019-1314-1Atypical hemolytic uremic syndromeAlternate complement pathwayEculizumabThrombotic microangiopathy |
| spellingShingle | Jan Menne Yahsou Delmas Fadi Fakhouri Christoph Licht Åsa Lommelé Enrico E. Minetti François Provôt Eric Rondeau Neil S. Sheerin Jimmy Wang Laurent E. Weekers Larry A. Greenbaum Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study BMC Nephrology Atypical hemolytic uremic syndrome Alternate complement pathway Eculizumab Thrombotic microangiopathy |
| title | Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study |
| title_full | Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study |
| title_fullStr | Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study |
| title_full_unstemmed | Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study |
| title_short | Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study |
| title_sort | outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long term observational study |
| topic | Atypical hemolytic uremic syndrome Alternate complement pathway Eculizumab Thrombotic microangiopathy |
| url | http://link.springer.com/article/10.1186/s12882-019-1314-1 |
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