Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy in paediatric patients with multiple sclerosis: Results from the PARADIGMS study
Background: Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment. Objective: To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years....
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| Veröffentlicht in: | Multiple sclerosis 2021-05, Vol.27 (6), p.922-932 |
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| creator | Chitnis, Tanuja Banwell, Brenda Krupp, Lauren Arnold, Douglas L Bar-Or, Amit Brück, Wolfgang Giovannoni, Gavin Greenberg, Benjamin Ghezzi, Angelo Waubant, Emmanuelle Rostasy, Kevin Deiva, Kumaran Huppke, Peter Wolinsky, Jerry S Zhang, Ying Azmon, Amin K-Laflamme, Annik Karan, Rajesh Gärtner, Jutta |
| description | Background:
Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment.
Objective:
To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years.
Methods:
We assessed ALC at baseline, monthly till 3 months, and every 3 months (core phase) and with variable periodicity (extension phase) of Phase 3 PARADIGMS study (N = 215). Incidence rates (IRs) of infection-related adverse events (infAEs)/100 patient-years were analysed by on-study nadir ALC.
Results:
With fingolimod, ALC rapidly reduced to 29.9%–34.4% of baseline values within 2 weeks and remained stable thereafter; no relevant changes observed with interferon. IRs of infAEs were 67.6 with fingolimod and 61.8 with interferon; IR ratios with respect to interferon, overall: 1.09, by nadir ALC 0.2–0.4 × 109/L: 1.13 and >0.4 × 109/L: 0.91. Three patients had a single episode of ALC |
| doi_str_mv | 10.1177/1352458520936934 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_sage_</sourceid><recordid>TN_cdi_proquest_miscellaneous_2421112132</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458520936934</sage_id><sourcerecordid>2421112132</sourcerecordid><originalsourceid>FETCH-LOGICAL-p2114-c7c9df29cf5c11a3f4b9781322863a08063ed109e5224eab07e5fb1a8ca71e493</originalsourceid><addsrcrecordid>eNpdkctKxDAUhosoqKN7lwE3bqq5tJPG3eBlHFCUUdclk57YSNrUJkX6VL6iqSMIrs7t4z-H8yfJCcHnhHB-QVhOs7zIKRZsLli2kxyQjPMUC453Yx7H6TTfTw69f8cYc87yg-TrBZrO9dKirnfaWEBOIzs2Xe3UGAApN7TBI9lWqAcrg3Gtr02HPk2okWk1qJ_WttamfXPWNK5CoYZedmNEUCehMjL0RsU0GJj0fvBmsMF0caVXFnrnjb9Ea_Cx65HuXTOJoKfFenG9Wj48Ix-GajxK9rS0Ho5_4yx5vb15ubpL7x-Xq6vFfdpRQrJUcSUqTYXSuSJEMp1tBC8Io7SYM4kLPGdQESwgpzQDucEccr0hslCSE8gEmyVnW934lo8BfCgb4xVYK1twgy9pFvcQGhUjevoPfXdD38brSho9IYLHEKl0S3n5Bn8EweVkX_nfPvYNmOWP9A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2524197252</pqid></control><display><type>article</type><title>Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy in paediatric patients with multiple sclerosis: Results from the PARADIGMS study</title><source>SAGE Complete A-Z List</source><creator>Chitnis, Tanuja ; Banwell, Brenda ; Krupp, Lauren ; Arnold, Douglas L ; Bar-Or, Amit ; Brück, Wolfgang ; Giovannoni, Gavin ; Greenberg, Benjamin ; Ghezzi, Angelo ; Waubant, Emmanuelle ; Rostasy, Kevin ; Deiva, Kumaran ; Huppke, Peter ; Wolinsky, Jerry S ; Zhang, Ying ; Azmon, Amin ; K-Laflamme, Annik ; Karan, Rajesh ; Gärtner, Jutta</creator><creatorcontrib>Chitnis, Tanuja ; Banwell, Brenda ; Krupp, Lauren ; Arnold, Douglas L ; Bar-Or, Amit ; Brück, Wolfgang ; Giovannoni, Gavin ; Greenberg, Benjamin ; Ghezzi, Angelo ; Waubant, Emmanuelle ; Rostasy, Kevin ; Deiva, Kumaran ; Huppke, Peter ; Wolinsky, Jerry S ; Zhang, Ying ; Azmon, Amin ; K-Laflamme, Annik ; Karan, Rajesh ; Gärtner, Jutta</creatorcontrib><description>Background:
Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment.
Objective:
To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years.
Methods:
We assessed ALC at baseline, monthly till 3 months, and every 3 months (core phase) and with variable periodicity (extension phase) of Phase 3 PARADIGMS study (N = 215). Incidence rates (IRs) of infection-related adverse events (infAEs)/100 patient-years were analysed by on-study nadir ALC.
Results:
With fingolimod, ALC rapidly reduced to 29.9%–34.4% of baseline values within 2 weeks and remained stable thereafter; no relevant changes observed with interferon. IRs of infAEs were 67.6 with fingolimod and 61.8 with interferon; IR ratios with respect to interferon, overall: 1.09, by nadir ALC 0.2–0.4 × 109/L: 1.13 and >0.4 × 109/L: 0.91. Three patients had a single episode of ALC <0.2 × 109/L (core phase). No opportunistic infections were observed and infection risk did not increase during the extension phase.
Conclusion:
In paediatric patients, the overall incidence of infections was comparable between fingolimod and interferon. No association was observed between nadir ALC and infections in POMS, although sample size may have been too small to rule an association.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458520936934</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Cell number ; Infections ; Interferon ; Lymphocytes ; Multiple sclerosis ; Pediatrics ; Periodicity</subject><ispartof>Multiple sclerosis, 2021-05, Vol.27 (6), p.922-932</ispartof><rights>The Author(s), 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-8197-2762 ; 0000-0002-9897-4422 ; 0000-0001-9794-6481 ; 0000-0001-7003-807X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458520936934$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458520936934$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21799,27903,27904,43600,43601</link.rule.ids></links><search><creatorcontrib>Chitnis, Tanuja</creatorcontrib><creatorcontrib>Banwell, Brenda</creatorcontrib><creatorcontrib>Krupp, Lauren</creatorcontrib><creatorcontrib>Arnold, Douglas L</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Brück, Wolfgang</creatorcontrib><creatorcontrib>Giovannoni, Gavin</creatorcontrib><creatorcontrib>Greenberg, Benjamin</creatorcontrib><creatorcontrib>Ghezzi, Angelo</creatorcontrib><creatorcontrib>Waubant, Emmanuelle</creatorcontrib><creatorcontrib>Rostasy, Kevin</creatorcontrib><creatorcontrib>Deiva, Kumaran</creatorcontrib><creatorcontrib>Huppke, Peter</creatorcontrib><creatorcontrib>Wolinsky, Jerry S</creatorcontrib><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Azmon, Amin</creatorcontrib><creatorcontrib>K-Laflamme, Annik</creatorcontrib><creatorcontrib>Karan, Rajesh</creatorcontrib><creatorcontrib>Gärtner, Jutta</creatorcontrib><title>Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy in paediatric patients with multiple sclerosis: Results from the PARADIGMS study</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>Background:
Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment.
Objective:
To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years.
Methods:
We assessed ALC at baseline, monthly till 3 months, and every 3 months (core phase) and with variable periodicity (extension phase) of Phase 3 PARADIGMS study (N = 215). Incidence rates (IRs) of infection-related adverse events (infAEs)/100 patient-years were analysed by on-study nadir ALC.
Results:
With fingolimod, ALC rapidly reduced to 29.9%–34.4% of baseline values within 2 weeks and remained stable thereafter; no relevant changes observed with interferon. IRs of infAEs were 67.6 with fingolimod and 61.8 with interferon; IR ratios with respect to interferon, overall: 1.09, by nadir ALC 0.2–0.4 × 109/L: 1.13 and >0.4 × 109/L: 0.91. Three patients had a single episode of ALC <0.2 × 109/L (core phase). No opportunistic infections were observed and infection risk did not increase during the extension phase.
Conclusion:
In paediatric patients, the overall incidence of infections was comparable between fingolimod and interferon. No association was observed between nadir ALC and infections in POMS, although sample size may have been too small to rule an association.</description><subject>Cell number</subject><subject>Infections</subject><subject>Interferon</subject><subject>Lymphocytes</subject><subject>Multiple sclerosis</subject><subject>Pediatrics</subject><subject>Periodicity</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpdkctKxDAUhosoqKN7lwE3bqq5tJPG3eBlHFCUUdclk57YSNrUJkX6VL6iqSMIrs7t4z-H8yfJCcHnhHB-QVhOs7zIKRZsLli2kxyQjPMUC453Yx7H6TTfTw69f8cYc87yg-TrBZrO9dKirnfaWEBOIzs2Xe3UGAApN7TBI9lWqAcrg3Gtr02HPk2okWk1qJ_WttamfXPWNK5CoYZedmNEUCehMjL0RsU0GJj0fvBmsMF0caVXFnrnjb9Ea_Cx65HuXTOJoKfFenG9Wj48Ix-GajxK9rS0Ho5_4yx5vb15ubpL7x-Xq6vFfdpRQrJUcSUqTYXSuSJEMp1tBC8Io7SYM4kLPGdQESwgpzQDucEccr0hslCSE8gEmyVnW934lo8BfCgb4xVYK1twgy9pFvcQGhUjevoPfXdD38brSho9IYLHEKl0S3n5Bn8EweVkX_nfPvYNmOWP9A</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Chitnis, Tanuja</creator><creator>Banwell, Brenda</creator><creator>Krupp, Lauren</creator><creator>Arnold, Douglas L</creator><creator>Bar-Or, Amit</creator><creator>Brück, Wolfgang</creator><creator>Giovannoni, Gavin</creator><creator>Greenberg, Benjamin</creator><creator>Ghezzi, Angelo</creator><creator>Waubant, Emmanuelle</creator><creator>Rostasy, Kevin</creator><creator>Deiva, Kumaran</creator><creator>Huppke, Peter</creator><creator>Wolinsky, Jerry S</creator><creator>Zhang, Ying</creator><creator>Azmon, Amin</creator><creator>K-Laflamme, Annik</creator><creator>Karan, Rajesh</creator><creator>Gärtner, Jutta</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8197-2762</orcidid><orcidid>https://orcid.org/0000-0002-9897-4422</orcidid><orcidid>https://orcid.org/0000-0001-9794-6481</orcidid><orcidid>https://orcid.org/0000-0001-7003-807X</orcidid></search><sort><creationdate>202105</creationdate><title>Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy in paediatric patients with multiple sclerosis: Results from the PARADIGMS study</title><author>Chitnis, Tanuja ; Banwell, Brenda ; Krupp, Lauren ; Arnold, Douglas L ; Bar-Or, Amit ; Brück, Wolfgang ; Giovannoni, Gavin ; Greenberg, Benjamin ; Ghezzi, Angelo ; Waubant, Emmanuelle ; Rostasy, Kevin ; Deiva, Kumaran ; Huppke, Peter ; Wolinsky, Jerry S ; Zhang, Ying ; Azmon, Amin ; K-Laflamme, Annik ; Karan, Rajesh ; Gärtner, Jutta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p2114-c7c9df29cf5c11a3f4b9781322863a08063ed109e5224eab07e5fb1a8ca71e493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cell number</topic><topic>Infections</topic><topic>Interferon</topic><topic>Lymphocytes</topic><topic>Multiple sclerosis</topic><topic>Pediatrics</topic><topic>Periodicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chitnis, Tanuja</creatorcontrib><creatorcontrib>Banwell, Brenda</creatorcontrib><creatorcontrib>Krupp, Lauren</creatorcontrib><creatorcontrib>Arnold, Douglas L</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Brück, Wolfgang</creatorcontrib><creatorcontrib>Giovannoni, Gavin</creatorcontrib><creatorcontrib>Greenberg, Benjamin</creatorcontrib><creatorcontrib>Ghezzi, Angelo</creatorcontrib><creatorcontrib>Waubant, Emmanuelle</creatorcontrib><creatorcontrib>Rostasy, Kevin</creatorcontrib><creatorcontrib>Deiva, Kumaran</creatorcontrib><creatorcontrib>Huppke, Peter</creatorcontrib><creatorcontrib>Wolinsky, Jerry S</creatorcontrib><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Azmon, Amin</creatorcontrib><creatorcontrib>K-Laflamme, Annik</creatorcontrib><creatorcontrib>Karan, Rajesh</creatorcontrib><creatorcontrib>Gärtner, Jutta</creatorcontrib><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chitnis, Tanuja</au><au>Banwell, Brenda</au><au>Krupp, Lauren</au><au>Arnold, Douglas L</au><au>Bar-Or, Amit</au><au>Brück, Wolfgang</au><au>Giovannoni, Gavin</au><au>Greenberg, Benjamin</au><au>Ghezzi, Angelo</au><au>Waubant, Emmanuelle</au><au>Rostasy, Kevin</au><au>Deiva, Kumaran</au><au>Huppke, Peter</au><au>Wolinsky, Jerry S</au><au>Zhang, Ying</au><au>Azmon, Amin</au><au>K-Laflamme, Annik</au><au>Karan, Rajesh</au><au>Gärtner, Jutta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy in paediatric patients with multiple sclerosis: Results from the PARADIGMS study</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2021-05</date><risdate>2021</risdate><volume>27</volume><issue>6</issue><spage>922</spage><epage>932</epage><pages>922-932</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><abstract>Background:
Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment.
Objective:
To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years.
Methods:
We assessed ALC at baseline, monthly till 3 months, and every 3 months (core phase) and with variable periodicity (extension phase) of Phase 3 PARADIGMS study (N = 215). Incidence rates (IRs) of infection-related adverse events (infAEs)/100 patient-years were analysed by on-study nadir ALC.
Results:
With fingolimod, ALC rapidly reduced to 29.9%–34.4% of baseline values within 2 weeks and remained stable thereafter; no relevant changes observed with interferon. IRs of infAEs were 67.6 with fingolimod and 61.8 with interferon; IR ratios with respect to interferon, overall: 1.09, by nadir ALC 0.2–0.4 × 109/L: 1.13 and >0.4 × 109/L: 0.91. Three patients had a single episode of ALC <0.2 × 109/L (core phase). No opportunistic infections were observed and infection risk did not increase during the extension phase.
Conclusion:
In paediatric patients, the overall incidence of infections was comparable between fingolimod and interferon. No association was observed between nadir ALC and infections in POMS, although sample size may have been too small to rule an association.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><doi>10.1177/1352458520936934</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8197-2762</orcidid><orcidid>https://orcid.org/0000-0002-9897-4422</orcidid><orcidid>https://orcid.org/0000-0001-9794-6481</orcidid><orcidid>https://orcid.org/0000-0001-7003-807X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1352-4585 |
| ispartof | Multiple sclerosis, 2021-05, Vol.27 (6), p.922-932 |
| issn | 1352-4585 1477-0970 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2421112132 |
| source | SAGE Complete A-Z List |
| subjects | Cell number Infections Interferon Lymphocytes Multiple sclerosis Pediatrics Periodicity |
| title | Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy in paediatric patients with multiple sclerosis: Results from the PARADIGMS study |
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