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PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study
Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C). This phase 2 dose-finding study (NCT02890992) evaluated the efficacy, safety, and dose selection of proprotein convertase subtilisin/kexin type 9 (...
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| Published in: | Journal of clinical lipidology 2020-05, Vol.14 (3), p.322-330.e5 |
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| container_end_page | 330.e5 |
| container_issue | 3 |
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| container_title | Journal of clinical lipidology |
| container_volume | 14 |
| creator | Daniels, Stephen Caprio, Sonia Chaudhari, Umesh Manvelian, Garen Baccara-Dinet, Marie T. Brunet, Aurelie Scemama, Michel Loizeau, Virginie Bruckert, Eric |
| description | Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C).
This phase 2 dose-finding study (NCT02890992) evaluated the efficacy, safety, and dose selection of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab in pediatric HeFH patients.
HeFH patients (n = 42) who were aged 8–17 years, had body weight (BW) ≥25 kg, and had LDL-C ≥130 mg/dL despite optimal statin/other lipid-modifying therapies were enrolled in 4 cohorts according to BW: cohort #1: 30 mg ( |
| doi_str_mv | 10.1016/j.jacl.2020.03.001 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_03968086v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1933287420300441</els_id><sourcerecordid>2394889578</sourcerecordid><originalsourceid>FETCH-LOGICAL-c434t-e58ef630056d213b95714098cdf24eb936c6756f23da09c20004ffbea525832f3</originalsourceid><addsrcrecordid>eNp9kU9v1DAQxSMEoqXwBTggH-GQ4D-J4yAu1bbQqisVacuhJ8txJsQrZx1sp2g58NlxlNIjJ1ue37zxm5dlbwkuCCb8477YK20LiikuMCswJs-yUyJqnpe1aJ6ne8NYTkVdnmSvQthjXFU1rl5mJ4wylor8NPvzbbO7aZA5DKY10bgD-mXigJQ13ul5VG0qoQk6o6I3Gk0qGjjEsFIDRPDu9_GHmwPq1WisURYNxwm8HpyFsJQtjEZ9QncDoNuL-93u8h7dXF_sUIhzd3ydveiVDfDm8TzLvn-5vNtc5dvbr9eb822uS1bGHCoBPWfJAO8oYW1T1aTEjdBdT0tokxPN64r3lHUKN5pijMu-b0FVtBKM9uws-7DqDsrKyZtR-aN0ysir861c3jBruMCCP5DEvl_ZybufczIhRxM0WKsOkIxKyppSiPQFkVC6otq7EDz0T9oEyyUjuZdLRnLJKM2QKaPU9O5Rf25H6J5a_oWSgM8rAGkjDwa8DDptXacUPOgoO2f-p_8X1M2ieQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2394889578</pqid></control><display><type>article</type><title>PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study</title><source>ScienceDirect Journals</source><creator>Daniels, Stephen ; Caprio, Sonia ; Chaudhari, Umesh ; Manvelian, Garen ; Baccara-Dinet, Marie T. ; Brunet, Aurelie ; Scemama, Michel ; Loizeau, Virginie ; Bruckert, Eric</creator><creatorcontrib>Daniels, Stephen ; Caprio, Sonia ; Chaudhari, Umesh ; Manvelian, Garen ; Baccara-Dinet, Marie T. ; Brunet, Aurelie ; Scemama, Michel ; Loizeau, Virginie ; Bruckert, Eric</creatorcontrib><description>Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C).
This phase 2 dose-finding study (NCT02890992) evaluated the efficacy, safety, and dose selection of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab in pediatric HeFH patients.
HeFH patients (n = 42) who were aged 8–17 years, had body weight (BW) ≥25 kg, and had LDL-C ≥130 mg/dL despite optimal statin/other lipid-modifying therapies were enrolled in 4 cohorts according to BW: cohort #1: 30 mg (<50 kg) or 50 mg (≥50 kg) every 2 weeks (Q2W), #2: 40 mg (<50 kg) or 75 mg (≥50 kg) Q2W, #3: 75 mg (<50 kg) or 150 mg (≥50 kg) every 4 weeks (Q4W), #4: 150 mg (<50 kg) or 300 mg (≥50 kg) Q4W. Primary endpoint was LDL-C % change from baseline to week 8.
Mean age was 12.4 years and 95% of patients were on a statin. Baseline LDL-C levels were 160.0–188.9 mg/dL and free PCSK9 was 186.4–201.7 ng/mL across the cohorts. At week 8, the higher dose cohorts (2 and 4) demonstrated the greatest reductions in LDL-C (–46% and –45%, respectively). Free PCSK9 levels were lowest at week 8 in cohorts 2 and 4 (42.2 ng/mL and 8.6 ng/mL, respectively). Adverse events were reported in 50–90% of patients across the cohorts, and 2 patients discontinued due to adverse events.
In pediatric HeFH patients, LDL-C reductions were greatest in the higher dose cohorts. Alirocumab was generally well tolerated at all doses.
[Display omitted]
•Heterozygous familial hypercholesterolemia is underdiagnosed in children, placing them at risk of cardiovascular events.•Target low-density lipoprotein cholesterol levels are often not reached despite optimal lipid-modifying therapies.•We assessed the effects, safety, and doses of alirocumab in pediatric patients with heterozygous familial hypercholesterolemia.•Reductions in low-density lipoprotein cholesterol were observed across all assessed doses.•Overall, treatment with alirocumab was generally well tolerated.</description><identifier>ISSN: 1933-2874</identifier><identifier>EISSN: 1876-4789</identifier><identifier>DOI: 10.1016/j.jacl.2020.03.001</identifier><identifier>PMID: 32331936</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alirocumab ; Cardiovascular ; Heterozygous familial hypercholesterolemia ; Life Sciences ; PCSK9 inhibitor ; Pediatrics</subject><ispartof>Journal of clinical lipidology, 2020-05, Vol.14 (3), p.322-330.e5</ispartof><rights>2020 National Lipid Association</rights><rights>Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-e58ef630056d213b95714098cdf24eb936c6756f23da09c20004ffbea525832f3</citedby><cites>FETCH-LOGICAL-c434t-e58ef630056d213b95714098cdf24eb936c6756f23da09c20004ffbea525832f3</cites><orcidid>0000-0002-5491-1032 ; 0000-0002-5541-2083</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32331936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03968086$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Daniels, Stephen</creatorcontrib><creatorcontrib>Caprio, Sonia</creatorcontrib><creatorcontrib>Chaudhari, Umesh</creatorcontrib><creatorcontrib>Manvelian, Garen</creatorcontrib><creatorcontrib>Baccara-Dinet, Marie T.</creatorcontrib><creatorcontrib>Brunet, Aurelie</creatorcontrib><creatorcontrib>Scemama, Michel</creatorcontrib><creatorcontrib>Loizeau, Virginie</creatorcontrib><creatorcontrib>Bruckert, Eric</creatorcontrib><title>PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study</title><title>Journal of clinical lipidology</title><addtitle>J Clin Lipidol</addtitle><description>Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C).
This phase 2 dose-finding study (NCT02890992) evaluated the efficacy, safety, and dose selection of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab in pediatric HeFH patients.
HeFH patients (n = 42) who were aged 8–17 years, had body weight (BW) ≥25 kg, and had LDL-C ≥130 mg/dL despite optimal statin/other lipid-modifying therapies were enrolled in 4 cohorts according to BW: cohort #1: 30 mg (<50 kg) or 50 mg (≥50 kg) every 2 weeks (Q2W), #2: 40 mg (<50 kg) or 75 mg (≥50 kg) Q2W, #3: 75 mg (<50 kg) or 150 mg (≥50 kg) every 4 weeks (Q4W), #4: 150 mg (<50 kg) or 300 mg (≥50 kg) Q4W. Primary endpoint was LDL-C % change from baseline to week 8.
Mean age was 12.4 years and 95% of patients were on a statin. Baseline LDL-C levels were 160.0–188.9 mg/dL and free PCSK9 was 186.4–201.7 ng/mL across the cohorts. At week 8, the higher dose cohorts (2 and 4) demonstrated the greatest reductions in LDL-C (–46% and –45%, respectively). Free PCSK9 levels were lowest at week 8 in cohorts 2 and 4 (42.2 ng/mL and 8.6 ng/mL, respectively). Adverse events were reported in 50–90% of patients across the cohorts, and 2 patients discontinued due to adverse events.
In pediatric HeFH patients, LDL-C reductions were greatest in the higher dose cohorts. Alirocumab was generally well tolerated at all doses.
[Display omitted]
•Heterozygous familial hypercholesterolemia is underdiagnosed in children, placing them at risk of cardiovascular events.•Target low-density lipoprotein cholesterol levels are often not reached despite optimal lipid-modifying therapies.•We assessed the effects, safety, and doses of alirocumab in pediatric patients with heterozygous familial hypercholesterolemia.•Reductions in low-density lipoprotein cholesterol were observed across all assessed doses.•Overall, treatment with alirocumab was generally well tolerated.</description><subject>Alirocumab</subject><subject>Cardiovascular</subject><subject>Heterozygous familial hypercholesterolemia</subject><subject>Life Sciences</subject><subject>PCSK9 inhibitor</subject><subject>Pediatrics</subject><issn>1933-2874</issn><issn>1876-4789</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kU9v1DAQxSMEoqXwBTggH-GQ4D-J4yAu1bbQqisVacuhJ8txJsQrZx1sp2g58NlxlNIjJ1ue37zxm5dlbwkuCCb8477YK20LiikuMCswJs-yUyJqnpe1aJ6ne8NYTkVdnmSvQthjXFU1rl5mJ4wylor8NPvzbbO7aZA5DKY10bgD-mXigJQ13ul5VG0qoQk6o6I3Gk0qGjjEsFIDRPDu9_GHmwPq1WisURYNxwm8HpyFsJQtjEZ9QncDoNuL-93u8h7dXF_sUIhzd3ydveiVDfDm8TzLvn-5vNtc5dvbr9eb822uS1bGHCoBPWfJAO8oYW1T1aTEjdBdT0tokxPN64r3lHUKN5pijMu-b0FVtBKM9uws-7DqDsrKyZtR-aN0ysir861c3jBruMCCP5DEvl_ZybufczIhRxM0WKsOkIxKyppSiPQFkVC6otq7EDz0T9oEyyUjuZdLRnLJKM2QKaPU9O5Rf25H6J5a_oWSgM8rAGkjDwa8DDptXacUPOgoO2f-p_8X1M2ieQ</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Daniels, Stephen</creator><creator>Caprio, Sonia</creator><creator>Chaudhari, Umesh</creator><creator>Manvelian, Garen</creator><creator>Baccara-Dinet, Marie T.</creator><creator>Brunet, Aurelie</creator><creator>Scemama, Michel</creator><creator>Loizeau, Virginie</creator><creator>Bruckert, Eric</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-5491-1032</orcidid><orcidid>https://orcid.org/0000-0002-5541-2083</orcidid></search><sort><creationdate>20200501</creationdate><title>PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study</title><author>Daniels, Stephen ; Caprio, Sonia ; Chaudhari, Umesh ; Manvelian, Garen ; Baccara-Dinet, Marie T. ; Brunet, Aurelie ; Scemama, Michel ; Loizeau, Virginie ; Bruckert, Eric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-e58ef630056d213b95714098cdf24eb936c6756f23da09c20004ffbea525832f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alirocumab</topic><topic>Cardiovascular</topic><topic>Heterozygous familial hypercholesterolemia</topic><topic>Life Sciences</topic><topic>PCSK9 inhibitor</topic><topic>Pediatrics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Daniels, Stephen</creatorcontrib><creatorcontrib>Caprio, Sonia</creatorcontrib><creatorcontrib>Chaudhari, Umesh</creatorcontrib><creatorcontrib>Manvelian, Garen</creatorcontrib><creatorcontrib>Baccara-Dinet, Marie T.</creatorcontrib><creatorcontrib>Brunet, Aurelie</creatorcontrib><creatorcontrib>Scemama, Michel</creatorcontrib><creatorcontrib>Loizeau, Virginie</creatorcontrib><creatorcontrib>Bruckert, Eric</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of clinical lipidology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Daniels, Stephen</au><au>Caprio, Sonia</au><au>Chaudhari, Umesh</au><au>Manvelian, Garen</au><au>Baccara-Dinet, Marie T.</au><au>Brunet, Aurelie</au><au>Scemama, Michel</au><au>Loizeau, Virginie</au><au>Bruckert, Eric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study</atitle><jtitle>Journal of clinical lipidology</jtitle><addtitle>J Clin Lipidol</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>14</volume><issue>3</issue><spage>322</spage><epage>330.e5</epage><pages>322-330.e5</pages><issn>1933-2874</issn><eissn>1876-4789</eissn><abstract>Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C).
This phase 2 dose-finding study (NCT02890992) evaluated the efficacy, safety, and dose selection of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab in pediatric HeFH patients.
HeFH patients (n = 42) who were aged 8–17 years, had body weight (BW) ≥25 kg, and had LDL-C ≥130 mg/dL despite optimal statin/other lipid-modifying therapies were enrolled in 4 cohorts according to BW: cohort #1: 30 mg (<50 kg) or 50 mg (≥50 kg) every 2 weeks (Q2W), #2: 40 mg (<50 kg) or 75 mg (≥50 kg) Q2W, #3: 75 mg (<50 kg) or 150 mg (≥50 kg) every 4 weeks (Q4W), #4: 150 mg (<50 kg) or 300 mg (≥50 kg) Q4W. Primary endpoint was LDL-C % change from baseline to week 8.
Mean age was 12.4 years and 95% of patients were on a statin. Baseline LDL-C levels were 160.0–188.9 mg/dL and free PCSK9 was 186.4–201.7 ng/mL across the cohorts. At week 8, the higher dose cohorts (2 and 4) demonstrated the greatest reductions in LDL-C (–46% and –45%, respectively). Free PCSK9 levels were lowest at week 8 in cohorts 2 and 4 (42.2 ng/mL and 8.6 ng/mL, respectively). Adverse events were reported in 50–90% of patients across the cohorts, and 2 patients discontinued due to adverse events.
In pediatric HeFH patients, LDL-C reductions were greatest in the higher dose cohorts. Alirocumab was generally well tolerated at all doses.
[Display omitted]
•Heterozygous familial hypercholesterolemia is underdiagnosed in children, placing them at risk of cardiovascular events.•Target low-density lipoprotein cholesterol levels are often not reached despite optimal lipid-modifying therapies.•We assessed the effects, safety, and doses of alirocumab in pediatric patients with heterozygous familial hypercholesterolemia.•Reductions in low-density lipoprotein cholesterol were observed across all assessed doses.•Overall, treatment with alirocumab was generally well tolerated.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32331936</pmid><doi>10.1016/j.jacl.2020.03.001</doi><orcidid>https://orcid.org/0000-0002-5491-1032</orcidid><orcidid>https://orcid.org/0000-0002-5541-2083</orcidid><oa>free_for_read</oa></addata></record> |
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| source | ScienceDirect Journals |
| subjects | Alirocumab Cardiovascular Heterozygous familial hypercholesterolemia Life Sciences PCSK9 inhibitor Pediatrics |
| title | PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study |
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