| 词条 | Rituximab |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 458438457 | image = Rituximab.png | width = 300 | type = mab | mab_type = mab | source = xi/o | target = CD20 | tradename = Rituxan, MabThera, others[1] | Drugs.com = {{drugs.com|monograph|rituximab}} | pregnancy_US = C | pregnancy_category = (no adequate human studies) | legal_US = | legal_status = Rx-only | routes_of_administration = intravenous infusion only (never bolus or "push") | bioavailability = 100% (IV) | protein_bound = | metabolism = | elimination_half-life = 30 to 400 hours (varies by dose and length of treatment) | excretion = Uncertain: may undergo phagocytosis and catabolism in RES | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = none | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 174722-31-7 | ATC_prefix = L01 | ATC_suffix = XC02 | ATC_supplemental = | PubChem = | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00073 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 4F4X42SYQ6 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D02994 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1201576 | C=6416 | H=9874 | N=1688 | O=1987 | S=44 | molecular_weight = 143859.7 g/mol |drug_name=|alt=|caption=|MedlinePlus=|licence_EU=yes|pregnancy_AU=|licence_US=}}Rituximab, sold under the brand name Rituxan among others, is a medication used to treat certain autoimmune diseases and types of cancer.[2] It is used for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein-Barr virus-positive mucocutaneous ulcers.[2][2][3][4] It is given by slow injection into a vein.[5] Common side effects, which often occur within two hours of the medication being given, include rash, itchiness, low blood pressure, and shortness of breath.[5] Other severe side effects include reactivation of hepatitis B in those previously infected, progressive multifocal leukoencephalopathy, and toxic epidermal necrolysis.[5] It is unclear if use during pregnancy is safe for the baby.[5] Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells.[11] When it binds to this protein it triggers cell death.[5] Rituximab was approved for medical use in 1997.[6] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[7] The wholesale price in the developing world as of 2014 was US$148–496 per 100 mg.[8] In the United Kingdom this amount cost the NHS approximately £182 in 2015.[9] The average wholesale price in the United States of a typical treatment for rheumatoid arthritis (1,000 mg IV dose, 2 weeks apart) would have been $14,100 a month in 2014 ($705 per 100 mg)[10] but the patent expired in 2016.[11] A number of biosimilars have been launched.[11] Medical usesRituximab destroys both normal and malignant B cells that have CD20 on their surfaces and is therefore used to treat diseases which are characterized by having too many B cells, overactive B cells, or dysfunctional B cells. Blood cancersRituximab is used to treat cancers of the white blood system such as leukemias and lymphomas, including non-Hodgkin's lymphoma and lymphocyte predominant subtype, of Hodgkin's Lymphoma.[12] This also includes Waldenström's macroglobulinemia a type of NHL.[5] Autoimmune diseasesRituximab has been shown to be an effective rheumatoid arthritis treatment in three randomised controlled trials and is now licensed for use in refractory rheumatoid disease.[13] In the United States, it has been FDA-approved for use in combination with methotrexate (MTX) for reducing signs and symptoms in adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more anti-TNF-alpha therapy. In Europe, the license is slightly more restrictive: it is licensed for use in combination with MTX in patients with severe active RA who have had an inadequate response to one or more anti-TNF therapy.[14] There is some evidence for efficacy, but not necessarily safety, in a range of other autoimmune diseases, and rituximab is widely used off-label to treat difficult cases of multiple sclerosis,[15] systemic lupus erythematosus, chronic inflammatory demyelinating polyneuropathy and autoimmune anemias.[16] The most dangerous, although among the most rare, side effect is progressive multifocal leukoencephalopathy (PML) infection, which is usually fatal; however only a very small number of cases have been recorded occurring in autoimmune diseases.[16][17] Other autoimmune diseases that have been treated with rituximab include autoimmune hemolytic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura (TTP),[18] idiopathic thrombocytopenic purpura (ITP),[19][20] Evans syndrome,[21] vasculitis (e.g., granulomatosis with polyangiitis), bullous skin disorders (for example pemphigus, pemphigoid—with very encouraging results of approximately 85% rapid recovery in pemphigus, according to a 2006 study),[22] type 1 diabetes mellitus, Sjogren's syndrome, anti-NMDA receptor encephalitis and Devic's disease,[23] Graves' ophthalmopathy,[24] autoimmune pancreatitis,[25] Opsoclonus myoclonus syndrome (OMS),[26] and IgG4-related disease.[27] There is some evidence that it is ineffective in treating IgA-mediated autoimmune diseases.[28] Organ transplantsRituximab is being used off-label in the management of kidney transplant recipients. This drug may have some utility in transplants involving incompatible blood groups. It is also used as induction therapy in highly sensitized patients going for kidney transplantation. The use of rituximab has not been proven to be efficacious in this setting and like all depleting agents, carries with it the risk of infection.{{Citation needed|date=February 2011}} Adverse eventsSerious adverse events, which can cause death and disability, include:[29]
Two patients with systemic lupus erythematosus died of progressive multifocal leukoencephalopathy (PML) after being treated with rituximab. PML is caused by activation of JC virus, a common virus in the brain which is usually latent. Reactivation of the JC virus usually results in death or severe brain damage.[33] At least one patient with rheumatoid arthritis developed PML after treatment with rituximab.[34] Rituximab has been reported as a possible cofactor in a chronic Hepatitis E infection in a person with lymphoma. Hepatitis E infection is normally an acute infection, suggesting the drug in combination with lymphoma may have weakened the body's immune response to the virus.[35] Mechanisms of actionThe antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in differentiation, but it is absent on terminally differentiated plasma cells. CD20 does not shed, modulate or internalise. Although the function of CD20 is unknown, it may play a role in Ca2+ influx across plasma membranes, maintaining intracellular Ca2+ concentration and allowing activation of B cells. Rituximab tends to stick to one side of B cells, where CD20 is, forming a cap and drawing proteins over to that side. The presence of the cap changes the effectiveness of natural killer (NK) cells in destroying these B cells. When an NK cell latched onto the cap, it had an 80% success rate at killing the cell. In contrast, when the B cell lacked this asymmetric protein cluster, it was killed only 40% of the time.[37][38] The following effects have been found:[39]
The combined effect results in the elimination of B cells (including the cancerous ones) from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells. Rituximab binds to amino acids 170-173 and 182-185 on CD20, which are physically close to each other as a result of a disulfide bond between amino acids 167 and 183.[40] HistoryRituximab was developed by researcher Nabil Hanna and coworkers at IDEC Pharmaceuticals under the name IDEC-C2B8. The U.S. patent for the drug was issued in 1998 and expired in 2015.[41] Based on its safety and effectiveness in clinical trials,[42] rituximab was approved by the U.S. Food and Drug Administration in 1997 to treat B-cell non-Hodgkin lymphomas resistant to other chemotherapy regimens.[43] Rituximab, in combination with CHOP chemotherapy, is superior to CHOP alone in the treatment of diffuse large B-cell lymphoma and many other B-cell lymphomas.[44] In 2010 it was approved by the European Commission for maintenance treatment after initial treatment of follicular lymphoma.[45] Rituximab is currently co-marketed by Biogen and Genentech in the U.S., by Hoffmann–La Roche in Canada and the European Union, Chugai Pharmaceuticals, Zenyaku Kogyo in Japan and AryoGen in Iran.{{citation needed|date=April 2016}} It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[46] In 2014 Genentech reclassified rituxan as a specialty drug, a class of drugs that are only available through specialty distributors in the US.[57] Because wholesalers discounts and rebates no longer apply, hospitals would pay more.[47] Originally available for intravenous injection (e.g. over 2.5 hrs), in 2016 it gained EU approval in a formulation for subcutaneous injection for CLL.[48] Patents on the drug in expired in Europe in February 2013 and in the US in September 2016.[49] {{As of|2018|alt=By November 2018}}, several biosimilars had been approved across India, the European Union, Switzerland, Japan and Australia.[49][50] ResearchChronic fatigue syndromeA potential use for rituximab was identified by two Norwegian doctors who were treating people who had cancer with rituximab; two people also had chronic fatigue syndrome and the CFS improved.[51] As of 2017 this use had been explored in some small clinical trials and was undergoing some larger ones; it was unclear as of 2017 whether there is enough benefit in light of the known adverse effects, for rituximab to be a viable treatment for CFS.[51] IntrathecalFor CNS diseases, rituximab could be administered intrathecally and this possibility is under study.[52] Other anti-CD20 monoclonalsThe efficacy and success of Rituximab has led to some other anti-CD20 monoclonal antibodies being developed:
References1. ^Drugs.com [https://www.drugs.com/international/rituximab.html International brand names for rituximab] {{webarchive|url=https://web.archive.org/web/20160422111521/http://www.drugs.com/international/rituximab.html |date=2016-04-22 }} Page accessed April 1, 2016 2. ^{{Cite journal|last=Tandan|first=Rup|last2=Hehir|first2=Michael K.|last3=Waheed|first3=Waqar|last4=Howard|first4=Diantha B.|date=August 2017|title=Rituximab treatment of myasthenia gravis: A systematic review|journal=Muscle & Nerve|volume=56|issue=2|pages=185–196|doi=10.1002/mus.25597|issn=1097-4598|pmid=28164324}} 3. ^{{cite journal|last1=Singer|first1=O|last2=McCune|first2=WJ|title=Update on maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis.|journal=Current Opinion in Rheumatology|date=May 2017|volume=29|issue=3|pages=248–253|doi=10.1097/BOR.0000000000000382|pmid=28306595}} 4. ^{{cite journal | vauthors = Dojcinov SD, Fend F, Quintanilla-Martinez L | title = EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts | journal = Pathogens (Basel, Switzerland) | volume = 7 | issue = 1 | pages = 28| date = March 2018 | pmid = 29518976 | pmc = 5874754 | doi = 10.3390/pathogens7010028 | url = }} 5. ^1 2 3 4 5 6 7 {{cite web|title=Rituximab|url=https://www.drugs.com/monograph/rituximab.html|publisher=The American Society of Health-System Pharmacists|accessdate=8 December 2016|deadurl=no|archiveurl=https://web.archive.org/web/20160327001117/http://www.drugs.com/monograph/rituximab.html|archivedate=27 March 2016|df=}} 6. ^1 {{cite book|last1=Bosch|first1=Xavier|last2=Ramos-Casals|first2=Manuel|last3=Khamashta|first3=Munther A.|title=Drugs Targeting B-Cells in Autoimmune Diseases|date=2013|publisher=Springer Science & Business Media|isbn=9783034807067|pages=1–4|url=https://books.google.com/books?id=2l-4BAAAQBAJ&pg=PA4|language=en|deadurl=no|archiveurl=https://web.archive.org/web/20171105200138/https://books.google.com/books?id=2l-4BAAAQBAJ&pg=PA4|archivedate=2017-11-05|df=}} 7. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016|df=}} 8. ^{{cite web|title=Rituximab|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=1466&searchYear=2014|website=International Drug Price Indicator Guide|accessdate=28 November 2015}} 9. ^{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=638|edition=69}} 10. ^{{cite journal|title=Drugs for Rheumatoid Arthritis|journal=The Medical Letter|date=22 December 2014|volume=56|issue=1458|pages=127–32|url=http://secure.medicalletter.org/TML-article-1458a|subscription=yes}} 11. ^1 {{cite web|title=Rituximab Biosimilars Shown to Be Safe and Effective|url=https://www.medscape.com/viewarticle/883511|website=www.medscape.com|accessdate=29 November 2017|archiveurl=https://archive.today/20180315211628/https://www.medscape.com/viewarticle/883511|archive-date=15 March 2018|deadurl=yes|df=}} 12. ^{{cite journal |vauthors=Saini KS, ((Azim HA Jr)), Cocorocchio E, Vanazzi A, Saini ML, Raviele PR, Pruneri G, Peccatori FA | title = Rituximab in Hodgkin lymphoma: Is the target always a hit? | journal = Cancer Treat Rev | volume = 37 | pages = 385–90 | year = 2011 | pmid = 21183282 | doi = 10.1016/j.ctrv.2010.11.005 | issue = 5}} 13. ^{{cite journal |vauthors=Edwards J, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close D, Stevens R, Shaw T | title = Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis | journal = N Engl J Med | volume = 350 | issue = 25 | pages = 2572–81 | year = 2004 | pmid = 15201414 | doi = 10.1056/NEJMoa032534| url = http://discovery.ucl.ac.uk/6967/1/6967.pdf }} 14. ^{{cite journal|vauthors=Tak PP, Kalden JR | title = Advances in rheumatology: new targeted therapeutics| journal = Arthritis Research & Therapy| year = 2011| volume = 13| issue = Suppl 1| pages = S5| pmid = 21624184| doi = 10.1186/1478-6354-13-S1-S5| pmc = 3123966| doi-broken-date = 2019-02-08}} 15. ^{{cite journal|last1=McGinley|first1=MP|last2=Moss|first2=BP|last3=Cohen|first3=JA|title=Safety of monoclonal antibodies for the treatment of multiple sclerosis.|journal=Expert Opinion on Drug Safety|date=January 2017|volume=16|issue=1|pages=89–100|doi=10.1080/14740338.2017.1250881|pmid=27756172}} 16. ^1 {{cite web|url=http://www.northwestern.edu/newscenter/stories/2009/05/bennett.html|title=Popular Cancer Drug Linked to Often Fatal 'Brain Eating' Virus|last=Paul|first=Marla|date=May 20, 2009|publisher=Northwestern University News and Information|accessdate=2009-05-22|deadurl=no|archiveurl=https://web.archive.org/web/20100529073721/http://www.northwestern.edu/newscenter/stories/2009/05/bennett.html|archivedate=May 29, 2010|df=}} 17. ^{{cite journal |url=http://www.fda.gov/bbs/topics/NEWS/2006/NEW01532.html |title=Press Announcements |journal=Journal of Polymer Science B Polymer Physics |volume=8 |issue=10 |pages=1845 |accessdate=2013-04-29 |deadurl=no |archiveurl=https://web.archive.org/web/20090513023924/http://www.fda.gov/bbs/topics/NEWS/2006/NEW01532.html |archivedate=2009-05-13 |df= |bibcode=1970JPoSB...8.1845. |year=1970 |doi=10.1002/pol.1970.160081020 }} 18. ^{{cite journal | pmid = 26293834 | doi=10.1016/j.ejim.2015.07.021 | title=Rituximab in autoimmune thrombotic thrombocytopenic purpura: A success story. |date=August 2015 |vauthors=Froissart A, Veyradier A, Hié M, Benhamou Y, Coppo P | journal=Eur J Intern Med | volume=26 | issue=9 | pages=659–65}} 19. ^{{cite journal | pmid = 15795920 | doi=10.1002/ajh.20276 | volume=78 | issue=4 | title=Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura |date=April 2005 |vauthors=Braendstrup P, Bjerrum OW, Nielsen OJ, etal | journal=Am. J. Hematol. | pages=275–80}} 20. ^{{cite journal | author = Patel V, Mihatov N, Cooper N, Stasi R, Cunningham-Rundles S, Bussel JB | year = 2007 | title = Long-term responses seen with rituximab in patients with ITP | url = http://www.communityoncology.net/journal/articles/0402107.pdf | journal = Community Oncology | volume = 4 | issue = 2 | page = 107 | doi = 10.1016/s1548-5315(11)70061-4 | deadurl = no | archiveurl = https://web.archive.org/web/20070929061010/http://www.communityoncology.net/journal/articles/0402107.pdf | archivedate = 2007-09-29 | df = }} 21. ^{{cite journal | author = Shanafelt TD, Madueme HL, Wold RC, Tefferi A | year = 2003 | title = Rituximab for Immune Cytopenia in Adults: Idiopathic Thrombocytopenic Purpura, Autoimmune Hemolytic Anemia, and Evans Syndrome | url = http://www.mayoclinicproceedings.com/pdf/7811/7811a3.pdf | archive-url = https://web.archive.org/web/20060313055117/http://www.mayoclinicproceedings.com/pdf/7811/7811a3.pdf | dead-url = yes | archive-date = 2006-03-13 | journal = Mayo Clinic Proceedings | volume = 78 | issue = 11| pages = 1340–1346 | doi = 10.4065/78.11.1340 | pmid = 14601692 }} 22. ^{{Cite journal |title=Treatment of Pemphigus Vulgaris with Rituximab and Intravenous Immune Globulin |author1=A. Razzaque Ahmed, M.D. |author2=Zachary Spigelman, M.D. |author3=Lisa A. Cavacini, Ph.D. |author4=Marshall R. Posner, M.D. |journal=N Engl J Med |volume=355 |issue=17 |pages=1772–1779 |date=October 26, 2006 |doi=10.1056/nejmoa062930 |pmid=17065638}} 23. ^{{cite journal |vauthors=Jacob A, Weinshenker BG, Violich I, McLinskey N, Krupp L, Fox RJ, Wingerchuk DM, Boggild M, Constantinescu CS, Miller A, De Angelis T, Matiello M, Cree BA |title=Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients |journal=Arch Neurol |volume=65 |issue=11 |pages=1443–1448 |year=2008 |pmid=18779415 |doi=10.1001/archneur.65.11.noc80069 |url=http://archneur.ama-assn.org/cgi/content/full/65/11/1443 |deadurl=no |archiveurl=https://web.archive.org/web/20090304221809/http://archneur.ama-assn.org/cgi/content/full/65/11/1443 |archivedate=2009-03-04 |df= }} 24. ^{{cite web |url=http://www.ophthalmologyjournaloftheaao.com/article/S0161-6420%2809%2900548-X/abstract |title=Rituximab Treatment of Patients with Severe, Corticosteroid-Resistant Thyroid-Associated Ophthalmopathy |accessdate=2011-10-19 |deadurl=no |archiveurl=https://web.archive.org/web/20170822220531/http://www.ophthalmologyjournaloftheaao.com/article/S0161-6420(09)00548-X/abstract |archivedate=2017-08-22 |df= }} 25. ^{{cite journal |url=http://www.pancreapedia.org/reviews/immunomodulators-and-rituximab-in-management-of-autoimmune-pancreatitis |title=Immunomodulators and Rituximab in the Management of Autoimmune Pancreatitis |accessdate=2014-04-30 |deadurl=no |archiveurl=https://web.archive.org/web/20140502010340/http://www.pancreapedia.org/reviews/immunomodulators-and-rituximab-in-management-of-autoimmune-pancreatitis |archivedate=2014-05-02 |df= |doi=10.3998/panc.2013.20 }} 26. ^{{cite journal |doi=10.1542/peds.2004-0845 |pmid=15601813 |title=Immunologic and Clinical Responses to Rituximab in a Child with Opsoclonus-Myoclonus Syndrome |journal=Pediatrics |volume=115 |issue=1 |pages=e115–9 |year=2004 |last1=Pranzatelli |first1=M. R. }} 27. ^{{cite journal |doi=10.1002/art.39132 |pmid=25809420 |title=International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease |journal=Arthritis & Rheumatology |volume=67 |issue=7 |pages=1688–1699 |year=2015 |last1=Khosroshahi |first1=A. |last2=Wallace |first2=Z. S. |last3=Crowe |first3=J. L. |last4=Akamizu |first4=T. |last5=Azumi |first5=A. |last6=Carruthers |first6=M. N. |last7=Chari |first7=S. T. |last8=Della-Torre |first8=E. |last9=Frulloni |first9=L. |last10=Goto |first10=H. |last11=Hart |first11=P. A. |last12=Kamisawa |first12=T. |last13=Kawa |first13=S. |last14=Kawano |first14=M. |last15=Kim |first15=M. H. |last16=Kodama |first16=Y. |last17=Kubota |first17=K. |last18=Lerch |first18=M. M. |last19=Löhr |first19=M. |last20=Masaki |first20=Y. |last21=Matsui |first21=S. |last22=Mimori |first22=T. |last23=Nakamura |first23=S. |last24=Nakazawa |first24=T. |last25=Ohara |first25=H. |last26=Okazaki |first26=K. |last27=Ryu |first27=J.H. |last28=Saeki |first28=T. |last29=Schleinitz |first29=N. |last30=Shimatsu |first30=A. |displayauthors=29 }} 28. ^{{cite journal |vauthors=He Y, Shimoda M, Ono Y, Villalobos IB, Mitra A, Konia T, Grando SA, Zone JJ, Maverakis E | title = Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab | journal = JAMA Dermatol | volume = 151 | issue = 6 | pages = 646–50 | year = 2015 | pmid = 25901938 | doi = 10.1001/jamadermatol.2015.59}} 29. ^{{cite web |url=http://www.gene.com/gene/products/information/immunological/rituxan/insert.jsp |title=Genentech: Products - Product Information - Immunology - Rituxan RA Full Prescribing Information |accessdate=2007-12-03 |website= |deadurl=yes |archiveurl=https://web.archive.org/web/20071213221352/http://www.gene.com/gene/products/information/immunological/rituxan/insert.jsp |archivedate=2007-12-13 |df= }} 30. ^{{cite journal |doi=10.1002/art.34468 |pmid=22422012 |title=Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: Evolving role of biologic therapies |journal=Arthritis & Rheumatism |volume=64 |issue=9 |pages=3043–3051 |year=2012 |last1=Molloy |first1=Eamonn S. |last2=Calabrese |first2=Leonard H. }} 31. ^{{cite journal |vauthors=Burton C, Kaczmarski R, Jan-Mohamed R |title=Interstitial pneumonitis related to rituximab therapy |journal=N Engl J Med |volume=348 |issue=26 |pages=2690–1; discussion 2690–1 |year=2003 |pmid=12826649 |doi=10.1056/NEJM200306263482619}} 32. ^{{cite web |url=http://rochecanada.com/portal/servlet/staticfilesServlet?type=data&communityId=re753001&id=static/attachedfile/re7300002/re77300002/AttachedFile_04801.pdf |title=Reports of Bowel Obstruction and Perforation with RITUXAN (rituximab) |date=2006-11-10 |publisher=Roche Canada |deadurl=no |archiveurl=https://web.archive.org/web/20140327221239/http://rochecanada.com/portal/servlet/staticfilesServlet?type=data&communityId=re753001&id=static%2Fattachedfile%2Fre7300002%2Fre77300002%2FAttachedFile_04801.pdf |archivedate=2014-03-27 |df= }} 33. ^{{cite web |url=http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109106.htm |title=Rituximab (marketed as Rituxan) Information |website= |accessdate=15 November 2009 |deadurl=no |archiveurl=https://web.archive.org/web/20091115233717/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109106.htm |archivedate=15 November 2009 |df= }} 34. ^{{cite web |url=http://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%209411700.pdf |title=Rituximab, RA and PML |website= |accessdate=2008-09-14 |deadurl=no |archiveurl=https://web.archive.org/web/20080916215120/http://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%209411700.pdf |archivedate=2008-09-16 |df= }} 35. ^{{cite journal |doi=10.7326/0003-4819-150-6-200903170-00025 |title=Challenges in Reporting Meta-analyses of Diagnostic Accuracy Studies |journal=Annals of Internal Medicine |volume=150 |issue=6 |pages=430 |year=2009 |last1=Kriston |first1=Levente }} 36. ^{{cite journal|last=Seyfizadeh|first=Narges|author2=Seyfizadeh, Nayer |author3=Hasenkamp, J |author4=Huerta-Yepez, S |title=A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections.|journal=Crit Rev Oncol Hematol|volume=97|pages=275–290|pmid=26443686|doi=10.1016/j.critrevonc.2015.09.001 |year=2016}} 37. ^{{cite journal |url=http://www.kurzweilai.net/scientists-discover-why-a-specific-cancer-drug-is-so-effective |title=Scientists discover why a specific cancer drug is so effective |journal=Blood |volume=121 |issue=23 |pages=4694–4702 |doi=10.1182/blood-2013-02-482570 |pmid=23613524 |accessdate=2013-04-29 |deadurl=no |archiveurl=https://web.archive.org/web/20130503033228/http://www.kurzweilai.net/scientists-discover-why-a-specific-cancer-drug-is-so-effective |archivedate=2013-05-03 |df= |year=2013 |last1=Rudnicka |first1=D. |last2=Oszmiana |first2=A. |last3=Finch |first3=D. K. |last4=Strickland |first4=I. |last5=Schofield |first5=D. J. |last6=Lowe |first6=D. C. |last7=Sleeman |first7=M. A. |last8=Davis |first8=D. M. }} 38. ^{{cite journal |doi=10.1182/blood-2013-02-482570 |pmid=23613524 |title=Rituximab causes a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity |journal=Blood |volume=121 |issue=23 |pages=4694–4702 |year=2013 |last1=Rudnicka |first1=D. |last2=Oszmiana |first2=A. |last3=Finch |first3=D. K. |last4=Strickland |first4=I. |last5=Schofield |first5=D. J. |last6=Lowe |first6=D. C. |last7=Sleeman |first7=M. A. |last8=Davis |first8=D. M. }} 39. ^{{cite journal |doi=10.1136/ard.62.suppl_2.ii55 |pmid=14532151 |pmc=1766758 |title=B cell therapy for rheumatoid arthritis: The rituximab (anti-CD20) experience |journal=Annals of the Rheumatic Diseases |volume=62 |issue=90002 |pages=55ii–59 |year=2003 |last1=Shaw |first1=T. }} 40. ^{{cite journal | author = Binder M, Otto F, Mertelsmann R, Veelken H, Trepel M. | title = The epitope recognized by rituximab | journal = Blood | volume = 108 | issue = 6| pages =1975–1978 | year = 2006 | pmid = 16705086 | doi = 10.1182/blood-2006-04-014639}} 41. ^DrugBank DB00073 {{webarchive|url=https://web.archive.org/web/20140105002750/http://www.drugbank.ca/drugs/DB00073 |date=2014-01-05 }} 42. ^{{cite journal |vauthors=Maloney DG, Grillo-López AJ, White CA, etal |title=IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma |journal=Blood |volume=90 |issue=6 |pages=2188–95 |date=September 1997 |pmid=9310469 |doi= |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=9310469}} 43. ^{{cite journal |doi=10.1046/j.1523-5394.1998.006003195.x |title=Rituximab: A New Therapeutic Monoclonal Antibody for Non-Hodgkin's Lymphoma |journal=Cancer Practice |volume=6 |issue=3 |pages=195–197 |year=1998 |last1=Scott |first1=Shane D. }} 44. ^Harrison's Principles of Internal Medicine, Longo et al. McGraw Hill Medical 2011 page 931 45. ^{{cite news |url=http://www.genengnews.com/gen-news-highlights/roche-gets-ec-nod-for-follicular-lymphoma-maintenance-therapy/81244149/ |title=Roche Gets EC Nod for Follicular Lymphoma Maintenance Therapy |date=October 29, 2010 |deadurl=no |archiveurl=https://web.archive.org/web/20101031202519/http://www.genengnews.com/gen-news-highlights/roche-gets-ec-nod-for-follicular-lymphoma-maintenance-therapy/81244149/ |archivedate=October 31, 2010 |df= }} 46. ^{{cite web|url=http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf|title=www.who.int|format=|website=|accessdate=|deadurl=no|archiveurl=https://web.archive.org/web/20150513043105/http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf|archivedate=2015-05-13|df=}} 47. ^1 {{cite web | url=http://time.com/3541484/cancer-drug-price-hikes/ | title=Hospitals Furious at Cancer-Drug Price Hikes | work=Time | date=27 October 2014 | accessdate=26 October 2015 | author=Saporito, Bill | deadurl=no | archiveurl=https://web.archive.org/web/20151020062334/http://time.com/3541484/cancer-drug-price-hikes/ | archivedate=20 October 2015 | df= }} 48. ^{{cite web |url=http://www.biopharma-reporter.com/Bio-Developments/EU-approves-indication-for-subcutaneous-form-of-Roche-s-MabThera/ |title=EU approves second indication for subcutaneous form of Roche's rituximab |accessdate=2016-06-09 |deadurl=no |archiveurl=https://web.archive.org/web/20160607225341/http://www.biopharma-reporter.com/Bio-Developments/EU-approves-indication-for-subcutaneous-form-of-Roche-s-MabThera |archivedate=2016-06-07 |df= }} 49. ^1 {{Cite web|url=http://www.gabionline.net/Biosimilars/General/Biosimilars-of-rituximab|title=Biosimilars of Rituximab|last=|first=|publisher=Generics and Biosimilars Initiative|language=en-GB|archive-url=https://web.archive.org/web/20170331230914/http://www.gabionline.net/Biosimilars/General/Biosimilars-of-rituximab|archive-date=2017-03-31|dead-url=no|access-date=2017-04-29|date=14 April 2017|df=}} 50. ^{{Cite news|url=https://www.reuters.com/article/us-novartis-rituximab/novartis-abandons-effort-for-u-s-approval-of-biosimilar-rituximab-idUSKCN1N72NA|title=Novartis abandons effort for U.S. approval of biosimilar rituximab|last=Lahiri|first=Diptendu|date=2 November 2018|work=|access-date=3 November 2018|agency=Reuters|last2=Osterman|first2=Cynthia}} 51. ^1 {{cite journal |doi=10.1111/bph.13702 |pmid=28052319 |pmc=5301046 |title=Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: All roads lead to Rome |journal=British Journal of Pharmacology |volume=174 |issue=5 |pages=345–369 |year=2017 |last1=Castro-Marrero |first1=Jesus |last2=Sáez-Francàs |first2=Naia |last3=Santillo |first3=Dafna |last4=Alegre |first4=Jose }} 52. ^{{cite journal |last1=Bonnan |first1=M |last2=Ferrari |first2=S |last3=Bertandeau |first3=E |last4=Demasles |first4=S |last5=Krim |first5=E |last6=Miquel |first6=M |last7=Barroso |first7=B |title=Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials. |journal=Current Drug Targets |date=2014 |volume=15 |issue=13 |pages=1205–14 |pmid=25355180|doi=10.2174/1389450115666141029234644 }} 53. ^{{cite web |url=http://www.genmab.com/ScienceAndResearch/ProductsinDevelopment/HuMax-CD20.aspx |title=Genmab.com / HuMax-CD20 (ofatumumab) |accessdate=2007-12-03 |website= |archiveurl = https://web.archive.org/web/20070911144653/http://www.genmab.com/ScienceAndResearch/ProductsinDevelopment/HuMax-CD20.aspx |archivedate = 2007-09-11}} 54. ^{{cite web |url=http://www.healthvalue.net/Fc-structure.html |title=Fc-structure |accessdate=2007-12-03 |website= |deadurl=no |archiveurl=https://web.archive.org/web/20071110011928/http://www.healthvalue.net/Fc-structure.html |archivedate=2007-11-10 |df= }} 55. ^{{cite journal |title=Monoclonal antibodies targeting cancer: 'magic bullets' or just the trigger? |pmc=138676 |year=2001 |volume=3 |issue=2 |pmid=11250751 |last1=Eccles |first1=SA |pages=86–90 |journal=Breast Cancer Research : BCR |doi=10.1186/bcr276}} 56. ^{{cite journal |vauthors=Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB | title = Glycans in the immune system and The Altered Glycan Theory of Autoimmunity | journal = J Autoimmun | volume = 57 | issue = 6 | pages = 1–13 | year = 2015 | pmid = 25578468 | pmc = 4340844 | doi = 10.1016/j.jaut.2014.12.002}} External links
6 : Monoclonal antibodies for tumors|Orphan drugs|Specialty drugs|World Health Organization essential medicines|RTT|Genentech |
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