Clinic and genetic predictors in response to erenumab
Background and purpose Erenumab (ERE) is the first anticalcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE. Methods Prospective multicenter study involving 110 migraine patients starting ERE 70 mg mo...
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| Veröffentlicht in: | European journal of neurology 2022-04, Vol.29 (4), p.1209-1217 |
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| creator | Zecca, Chiara Cargnin, Sarah Schankin, Christoph Giannantoni, Nadia Mariagrazia Viana, Michele Maraffi, Isabella Riccitelli, Gianna Carla Sihabdeen, Shairin Terrazzino, Salvatore Gobbi, Claudio |
| description | Background and purpose
Erenumab (ERE) is the first anticalcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.
Methods
Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio‐demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine‐related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test‐6), and use of abortive medications, during 3 months before and after ERE start were collected. Real‐time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor‐like receptor and receptor activity‐modifying protein‐1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50‐RESP) and 75% responder patients (75‐RESP).
Results
At month 3, MMDs decreased from 17.2 to 9.2 (p |
| doi_str_mv | 10.1111/ene.15236 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9306465</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2615299697</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4246-8f359f18ecba809099decbe76c4ab29660eeb639df3f19f14f5771c7b93bee193</originalsourceid><addsrcrecordid>eNp1kU1LxDAQhoMo7vpx8A9IwYseqknTps1FkGX9gEUveg5pOl0j3WRNWmX_vaOrooLJIRPy8DB5h5ADRk8ZrjNwcMqKjIsNMma5qFLGOdvEmhcsLRhlI7IT4xOlNCszuk1GPJeiwNuYFJPOOmsS7Zpkjp4e62WAxpreh5hYlwSIS-8iJL1PIIAbFrreI1ut7iLsf5675OFyej-5Tmd3VzeTi1lq8iwXadXyQrasAlPrikoqZYMllMLkus6kEBSgFlw2LW8ZgnlblCUzZS15DcAk3yXna-9yqBfQGHB90J1aBrvQYaW8tur3i7OPau5flORU5KJAwfGnIPjnAWKvFjYa6DrtwA9RZQJzk1LIEtGjP-iTH4LD7yHFcVNeMaRO1pQJPsYA7XczjKr3YSgMUX0MA9nDn91_k1_pI3C2Bl5tB6v_TWp6O10r3wDje5M-</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2636360381</pqid></control><display><type>article</type><title>Clinic and genetic predictors in response to erenumab</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Zecca, Chiara ; Cargnin, Sarah ; Schankin, Christoph ; Giannantoni, Nadia Mariagrazia ; Viana, Michele ; Maraffi, Isabella ; Riccitelli, Gianna Carla ; Sihabdeen, Shairin ; Terrazzino, Salvatore ; Gobbi, Claudio</creator><creatorcontrib>Zecca, Chiara ; Cargnin, Sarah ; Schankin, Christoph ; Giannantoni, Nadia Mariagrazia ; Viana, Michele ; Maraffi, Isabella ; Riccitelli, Gianna Carla ; Sihabdeen, Shairin ; Terrazzino, Salvatore ; Gobbi, Claudio</creatorcontrib><description>Background and purpose
Erenumab (ERE) is the first anticalcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.
Methods
Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio‐demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine‐related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test‐6), and use of abortive medications, during 3 months before and after ERE start were collected. Real‐time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor‐like receptor and receptor activity‐modifying protein‐1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50‐RESP) and 75% responder patients (75‐RESP).
Results
At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50‐RESP, and 30/110 (27.3%) were 75‐RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008–1.120], p = 0.024), number of failed preventive medications (0.753 [0.600–0.946], p = 0.015), and MIDAS score (1.011 [1.002–1.020], p = 0.017) were associated with 75‐RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75‐RESP (per G allele OR [95% CI]: 0.53 [0.29–0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28–1.10], p = 0.09]).
Conclusions
In this real‐word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.
Clinical predictors of a 75% or higher reduction in monthly migraine days during 3‐month erenumab treatment were older age at migraine onset, lower number of failed preventive medications, and higher migraine burden as measured by the Migraine Disability Assessment score questionnaire. At multivariate analysis, no single nucleotide polymorphisms (SNPs) at calcitonin receptor like receptor (CALCRL) and RAMP1 were found to be an independent predictor of treatment response, despite a modest effect of SNPs cannot be ruled out due to the limited sample size of our study.</description><identifier>ISSN: 1351-5101</identifier><identifier>EISSN: 1468-1331</identifier><identifier>DOI: 10.1111/ene.15236</identifier><identifier>PMID: 34965002</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Alleles ; anti‐CGRP antibodies ; Calcitonin ; Confidence intervals ; Demographics ; Demography ; erenumab ; Genetic diversity ; Genetic variance ; Headache ; Impact tests ; Migraine ; Monoclonal antibodies ; Original ; Patients ; Polymerase chain reaction ; predictors ; Receptor activity modifying proteins ; Receptors ; Regression analysis ; Regression models ; Statistical analysis ; treatment response</subject><ispartof>European journal of neurology, 2022-04, Vol.29 (4), p.1209-1217</ispartof><rights>2021 The Authors. published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.</rights><rights>2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4246-8f359f18ecba809099decbe76c4ab29660eeb639df3f19f14f5771c7b93bee193</citedby><cites>FETCH-LOGICAL-c4246-8f359f18ecba809099decbe76c4ab29660eeb639df3f19f14f5771c7b93bee193</cites><orcidid>0000-0002-7554-0664 ; 0000-0002-9990-3431 ; 0000-0003-4356-8109 ; 0000-0002-1202-5534</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fene.15236$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fene.15236$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34965002$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zecca, Chiara</creatorcontrib><creatorcontrib>Cargnin, Sarah</creatorcontrib><creatorcontrib>Schankin, Christoph</creatorcontrib><creatorcontrib>Giannantoni, Nadia Mariagrazia</creatorcontrib><creatorcontrib>Viana, Michele</creatorcontrib><creatorcontrib>Maraffi, Isabella</creatorcontrib><creatorcontrib>Riccitelli, Gianna Carla</creatorcontrib><creatorcontrib>Sihabdeen, Shairin</creatorcontrib><creatorcontrib>Terrazzino, Salvatore</creatorcontrib><creatorcontrib>Gobbi, Claudio</creatorcontrib><title>Clinic and genetic predictors in response to erenumab</title><title>European journal of neurology</title><addtitle>Eur J Neurol</addtitle><description>Background and purpose
Erenumab (ERE) is the first anticalcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.
Methods
Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio‐demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine‐related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test‐6), and use of abortive medications, during 3 months before and after ERE start were collected. Real‐time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor‐like receptor and receptor activity‐modifying protein‐1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50‐RESP) and 75% responder patients (75‐RESP).
Results
At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50‐RESP, and 30/110 (27.3%) were 75‐RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008–1.120], p = 0.024), number of failed preventive medications (0.753 [0.600–0.946], p = 0.015), and MIDAS score (1.011 [1.002–1.020], p = 0.017) were associated with 75‐RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75‐RESP (per G allele OR [95% CI]: 0.53 [0.29–0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28–1.10], p = 0.09]).
Conclusions
In this real‐word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.
Clinical predictors of a 75% or higher reduction in monthly migraine days during 3‐month erenumab treatment were older age at migraine onset, lower number of failed preventive medications, and higher migraine burden as measured by the Migraine Disability Assessment score questionnaire. At multivariate analysis, no single nucleotide polymorphisms (SNPs) at calcitonin receptor like receptor (CALCRL) and RAMP1 were found to be an independent predictor of treatment response, despite a modest effect of SNPs cannot be ruled out due to the limited sample size of our study.</description><subject>Alleles</subject><subject>anti‐CGRP antibodies</subject><subject>Calcitonin</subject><subject>Confidence intervals</subject><subject>Demographics</subject><subject>Demography</subject><subject>erenumab</subject><subject>Genetic diversity</subject><subject>Genetic variance</subject><subject>Headache</subject><subject>Impact tests</subject><subject>Migraine</subject><subject>Monoclonal antibodies</subject><subject>Original</subject><subject>Patients</subject><subject>Polymerase chain reaction</subject><subject>predictors</subject><subject>Receptor activity modifying proteins</subject><subject>Receptors</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Statistical analysis</subject><subject>treatment response</subject><issn>1351-5101</issn><issn>1468-1331</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp1kU1LxDAQhoMo7vpx8A9IwYseqknTps1FkGX9gEUveg5pOl0j3WRNWmX_vaOrooLJIRPy8DB5h5ADRk8ZrjNwcMqKjIsNMma5qFLGOdvEmhcsLRhlI7IT4xOlNCszuk1GPJeiwNuYFJPOOmsS7Zpkjp4e62WAxpreh5hYlwSIS-8iJL1PIIAbFrreI1ut7iLsf5675OFyej-5Tmd3VzeTi1lq8iwXadXyQrasAlPrikoqZYMllMLkus6kEBSgFlw2LW8ZgnlblCUzZS15DcAk3yXna-9yqBfQGHB90J1aBrvQYaW8tur3i7OPau5flORU5KJAwfGnIPjnAWKvFjYa6DrtwA9RZQJzk1LIEtGjP-iTH4LD7yHFcVNeMaRO1pQJPsYA7XczjKr3YSgMUX0MA9nDn91_k1_pI3C2Bl5tB6v_TWp6O10r3wDje5M-</recordid><startdate>202204</startdate><enddate>202204</enddate><creator>Zecca, Chiara</creator><creator>Cargnin, Sarah</creator><creator>Schankin, Christoph</creator><creator>Giannantoni, Nadia Mariagrazia</creator><creator>Viana, Michele</creator><creator>Maraffi, Isabella</creator><creator>Riccitelli, Gianna Carla</creator><creator>Sihabdeen, Shairin</creator><creator>Terrazzino, Salvatore</creator><creator>Gobbi, Claudio</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7554-0664</orcidid><orcidid>https://orcid.org/0000-0002-9990-3431</orcidid><orcidid>https://orcid.org/0000-0003-4356-8109</orcidid><orcidid>https://orcid.org/0000-0002-1202-5534</orcidid></search><sort><creationdate>202204</creationdate><title>Clinic and genetic predictors in response to erenumab</title><author>Zecca, Chiara ; Cargnin, Sarah ; Schankin, Christoph ; Giannantoni, Nadia Mariagrazia ; Viana, Michele ; Maraffi, Isabella ; Riccitelli, Gianna Carla ; Sihabdeen, Shairin ; Terrazzino, Salvatore ; Gobbi, Claudio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4246-8f359f18ecba809099decbe76c4ab29660eeb639df3f19f14f5771c7b93bee193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alleles</topic><topic>anti‐CGRP antibodies</topic><topic>Calcitonin</topic><topic>Confidence intervals</topic><topic>Demographics</topic><topic>Demography</topic><topic>erenumab</topic><topic>Genetic diversity</topic><topic>Genetic variance</topic><topic>Headache</topic><topic>Impact tests</topic><topic>Migraine</topic><topic>Monoclonal antibodies</topic><topic>Original</topic><topic>Patients</topic><topic>Polymerase chain reaction</topic><topic>predictors</topic><topic>Receptor activity modifying proteins</topic><topic>Receptors</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Statistical analysis</topic><topic>treatment response</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zecca, Chiara</creatorcontrib><creatorcontrib>Cargnin, Sarah</creatorcontrib><creatorcontrib>Schankin, Christoph</creatorcontrib><creatorcontrib>Giannantoni, Nadia Mariagrazia</creatorcontrib><creatorcontrib>Viana, Michele</creatorcontrib><creatorcontrib>Maraffi, Isabella</creatorcontrib><creatorcontrib>Riccitelli, Gianna Carla</creatorcontrib><creatorcontrib>Sihabdeen, Shairin</creatorcontrib><creatorcontrib>Terrazzino, Salvatore</creatorcontrib><creatorcontrib>Gobbi, Claudio</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zecca, Chiara</au><au>Cargnin, Sarah</au><au>Schankin, Christoph</au><au>Giannantoni, Nadia Mariagrazia</au><au>Viana, Michele</au><au>Maraffi, Isabella</au><au>Riccitelli, Gianna Carla</au><au>Sihabdeen, Shairin</au><au>Terrazzino, Salvatore</au><au>Gobbi, Claudio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinic and genetic predictors in response to erenumab</atitle><jtitle>European journal of neurology</jtitle><addtitle>Eur J Neurol</addtitle><date>2022-04</date><risdate>2022</risdate><volume>29</volume><issue>4</issue><spage>1209</spage><epage>1217</epage><pages>1209-1217</pages><issn>1351-5101</issn><eissn>1468-1331</eissn><abstract>Background and purpose
Erenumab (ERE) is the first anticalcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.
Methods
Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio‐demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine‐related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test‐6), and use of abortive medications, during 3 months before and after ERE start were collected. Real‐time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor‐like receptor and receptor activity‐modifying protein‐1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50‐RESP) and 75% responder patients (75‐RESP).
Results
At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50‐RESP, and 30/110 (27.3%) were 75‐RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008–1.120], p = 0.024), number of failed preventive medications (0.753 [0.600–0.946], p = 0.015), and MIDAS score (1.011 [1.002–1.020], p = 0.017) were associated with 75‐RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75‐RESP (per G allele OR [95% CI]: 0.53 [0.29–0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28–1.10], p = 0.09]).
Conclusions
In this real‐word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.
Clinical predictors of a 75% or higher reduction in monthly migraine days during 3‐month erenumab treatment were older age at migraine onset, lower number of failed preventive medications, and higher migraine burden as measured by the Migraine Disability Assessment score questionnaire. At multivariate analysis, no single nucleotide polymorphisms (SNPs) at calcitonin receptor like receptor (CALCRL) and RAMP1 were found to be an independent predictor of treatment response, despite a modest effect of SNPs cannot be ruled out due to the limited sample size of our study.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>34965002</pmid><doi>10.1111/ene.15236</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7554-0664</orcidid><orcidid>https://orcid.org/0000-0002-9990-3431</orcidid><orcidid>https://orcid.org/0000-0003-4356-8109</orcidid><orcidid>https://orcid.org/0000-0002-1202-5534</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Alleles anti‐CGRP antibodies Calcitonin Confidence intervals Demographics Demography erenumab Genetic diversity Genetic variance Headache Impact tests Migraine Monoclonal antibodies Original Patients Polymerase chain reaction predictors Receptor activity modifying proteins Receptors Regression analysis Regression models Statistical analysis treatment response |
| title | Clinic and genetic predictors in response to erenumab |
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