{"title":"抗cd20细胞治疗多发性硬化症- Ocrelizumab的固定剂量计划是过度杀伤。","authors":"Jagannadha Avasarala","doi":"10.1177/1177392817737515","DOIUrl":null,"url":null,"abstract":"<p><p>Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this-Why does the drug need to be dosed at fixed intervals and not <i>based</i> on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2017-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392817737515","citationCount":"11","resultStr":"{\"title\":\"Anti-CD20 Cell Therapies in Multiple Sclerosis-A Fixed Dosing Schedule for Ocrelizumab is Overkill.\",\"authors\":\"Jagannadha Avasarala\",\"doi\":\"10.1177/1177392817737515\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this-Why does the drug need to be dosed at fixed intervals and not <i>based</i> on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.</p>\",\"PeriodicalId\":11326,\"journal\":{\"name\":\"Drug Target Insights\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2017-10-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1177/1177392817737515\",\"citationCount\":\"11\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Target Insights\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/1177392817737515\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Target Insights","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/1177392817737515","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Anti-CD20 Cell Therapies in Multiple Sclerosis-A Fixed Dosing Schedule for Ocrelizumab is Overkill.
Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this-Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.