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A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20—Yet Progress Continues
Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the...
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| Published in: | Neurotherapeutics 2021-07, Vol.18 (3), p.1602-1622 |
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| creator | Frisch, Esther S. Pretzsch, Roxanne Weber, Martin S. |
| description | Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the last decades, monoclonal antibodies (mabs) against the surface protein CD20 have been intensively studied as a B cell targeting therapy in relapsing MS (RMS) as well as primary progressive MS (PPMS). Pivotal studies on anti-CD20 therapy in RMS showed remarkable clinical and radiological effects, especially on acute inflammation and relapse biology. These results paved the way for further research on the implication of B cells in the pathogenesis of MS. Besides controlling relapse development in RMS, ocrelizumab (OCR) also showed clinical benefits in patients with PPMS and became the first approved drug for this disease course. In this review, we provide an overview of the current anti-CD20 mabs used or tested for the treatment of MS—namely rituximab (RTX), OCR, ofatumumab (OFA), and ublituximab (UB). Besides their effectiveness, we also discuss possible limitations and safety concerns especially in regard to long-term treatment, both for this class of drugs overall as well as for each anti-CD20 mab individually. Additionally, we elucidate to what extent anti-CD20 therapy may alter the function of other immune cells, both directly or indirectly. Finally, we cover the current knowledge on repopulation of CD20
+
cells after cessation of anti-CD20 treatment and discuss future aspirations towards alternative, further developed B cell silencing therapies. |
| doi_str_mv | 10.1007/s13311-021-01048-z |
| format | article |
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drug therapy</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis, Chronic Progressive - drug therapy</subject><subject>Multiple Sclerosis, Chronic Progressive - immunology</subject><subject>Multiple Sclerosis, Relapsing-Remitting - drug therapy</subject><subject>Multiple Sclerosis, Relapsing-Remitting - immunology</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Neurosurgery</subject><subject>Pathogenesis</subject><subject>Rituximab</subject><subject>Rituximab - pharmacology</subject><subject>Rituximab - therapeutic use</subject><issn>1933-7213</issn><issn>1878-7479</issn><issn>1878-7479</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kctuFDEQRVsIRELgB1ggS2zYNPjVfrBAGg0QImUEEmHBynJ3lyeOPPZgdyMlq3xEvpAvicmE8FiwsGypTt0q39s0Twl-STCWrwphjJAW03oI5qq9uNfsEyVVK7nU9-tbM9ZKSthe86iUM4w7xrR62OwxphSWTO03boFWPkCZUgTkI1rNYfLbAOjzECCn4gs6OYVst-ev0SrFNIQUbUCLOPk-jR4KWqytj2VCy7cU_7i8-goT-pTTOkMpaJkqF2coj5sHzoYCT27vg-bL-3cnyw_t8cfDo-XiuB245FPL8KhFZ3vXd0z1_eg0dYCZdEqPSjsu7KhHKdnIcUddD3zoqJWcWCqElZizg-bNTnc79xsYB4hTtsFss9_YfG6S9ebvSvSnZp2-GyWwxkJUgRe3Ajl9q4tPZuPLACHYCGkuhnZEUEqVYBV9_g96luZc3amUqF4TUWOoFN1RQ3WzZHB3yxBsfsZodjGaGqO5idFc1KZnf37jruVXbhVgO6DUUlxD_j37P7LXNxOq1g</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Frisch, Esther S.</creator><creator>Pretzsch, Roxanne</creator><creator>Weber, Martin S.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8409-0389</orcidid></search><sort><creationdate>20210701</creationdate><title>A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20—Yet Progress Continues</title><author>Frisch, Esther S. ; Pretzsch, Roxanne ; Weber, Martin S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-30d965abfb538bbdf92fe037f89d89f46ad9d773d4052fbe4c52a741a266a7043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies, Monoclonal - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurotherapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frisch, Esther S.</au><au>Pretzsch, Roxanne</au><au>Weber, Martin S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20—Yet Progress Continues</atitle><jtitle>Neurotherapeutics</jtitle><stitle>Neurotherapeutics</stitle><addtitle>Neurotherapeutics</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>18</volume><issue>3</issue><spage>1602</spage><epage>1622</epage><pages>1602-1622</pages><issn>1933-7213</issn><issn>1878-7479</issn><eissn>1878-7479</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-3</notes><notes>content type line 23</notes><notes>ObjectType-Review-1</notes><abstract>Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the last decades, monoclonal antibodies (mabs) against the surface protein CD20 have been intensively studied as a B cell targeting therapy in relapsing MS (RMS) as well as primary progressive MS (PPMS). Pivotal studies on anti-CD20 therapy in RMS showed remarkable clinical and radiological effects, especially on acute inflammation and relapse biology. These results paved the way for further research on the implication of B cells in the pathogenesis of MS. Besides controlling relapse development in RMS, ocrelizumab (OCR) also showed clinical benefits in patients with PPMS and became the first approved drug for this disease course. In this review, we provide an overview of the current anti-CD20 mabs used or tested for the treatment of MS—namely rituximab (RTX), OCR, ofatumumab (OFA), and ublituximab (UB). Besides their effectiveness, we also discuss possible limitations and safety concerns especially in regard to long-term treatment, both for this class of drugs overall as well as for each anti-CD20 mab individually. Additionally, we elucidate to what extent anti-CD20 therapy may alter the function of other immune cells, both directly or indirectly. Finally, we cover the current knowledge on repopulation of CD20
+
cells after cessation of anti-CD20 treatment and discuss future aspirations towards alternative, further developed B cell silencing therapies.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>33880738</pmid><doi>10.1007/s13311-021-01048-z</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0001-8409-0389</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized - pharmacology Antibodies, Monoclonal, Humanized - therapeutic use Antigens, CD20 - immunology B-Lymphocytes, Regulatory - drug effects B-Lymphocytes, Regulatory - immunology Biomedical and Life Sciences Biomedicine CD20 antigen Central nervous system Clinical Trials as Topic - methods Current Perspectives Current s Humans Immunosuppressive agents Immunotherapy Inflammatory diseases Lymphocytes B Monoclonal antibodies Multiple sclerosis Multiple Sclerosis - drug therapy Multiple Sclerosis - immunology Multiple Sclerosis, Chronic Progressive - drug therapy Multiple Sclerosis, Chronic Progressive - immunology Multiple Sclerosis, Relapsing-Remitting - drug therapy Multiple Sclerosis, Relapsing-Remitting - immunology Neurobiology Neurology Neurosciences Neurosurgery Pathogenesis Rituximab Rituximab - pharmacology Rituximab - therapeutic use |
| title | A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20—Yet Progress Continues |
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