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Revision as of 10:21, 1 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,054 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit Latest revision as of 08:07, 14 January 2025 edit undoRememberOrwell (talk | contribs)325 edits SimplifyTag: 2017 wikitext editor 
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{{Short description|Biopharmaceutical drug}}
{{Drugbox
{{Use dmy dates|date=June 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed | Verifiedfields = changed
| verifiedrevid = 456484325 | verifiedrevid = 458438457
| image = Rituximab.png
| width = 300
| alt =
| caption =


<!--Monoclonal antibody data--> <!-- Monoclonal antibody data -->
| type = mab | type = mab
| mab_type = mab | mab_type = mab
Line 9: Line 16:
| target = ] | target = ]


<!--Clinical data--> <!-- Clinical data -->
| tradename = Rituxan | pronounce =
| tradename = Rituxan, Mabthera, others
| Drugs.com = {{drugs.com|monograph|rituximab}} | Drugs.com = {{drugs.com|monograph|rituximab}}
| pregnancy_US = C | MedlinePlus = a607038
| DailyMedID = Rituximab
| pregnancy_category = (no adequate human studies)
| pregnancy_AU = C
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Rituximab Use During Pregnancy | website=Drugs.com | date=16 December 2019 | url=https://www.drugs.com/pregnancy/rituximab.html | access-date=2 February 2020 | archive-date=30 August 2019 | archive-url=https://web.archive.org/web/20190830220734/https://www.drugs.com/pregnancy/rituximab.html | url-status=live }}</ref>
| pregnancy_category=
| routes_of_administration = ]
| class = ]
| ATC_prefix = L01
| ATC_suffix = FA01
| ATC_supplemental =
| biosimilars = rituximab-abbs,<ref name="Truxima FDA label">{{cite web | title=Truxima- rituximab-abbs injection solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9af3ddc7-4217-417a-ac89-8704edc5bc44 | access-date=26 March 2021 | archive-date=25 March 2021 | archive-url=https://web.archive.org/web/20210325082706/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9af3ddc7-4217-417a-ac89-8704edc5bc44 | url-status=live }}</ref> rituximab-pvvr,<ref name="Ruxience FDA label">{{cite web | title=Ruxience- rituximab-pvvr injection solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f941fc61-f7a3-4e4a-ab7c-87c1667fa05b | access-date=26 March 2021}}</ref> rituximab-arrx,<ref name="Riabni FDA label">{{cite web | title=Riabni- rituximab-arrx injection solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da1c4de7-0e5b-4f72-97ec-7a8d368f085f | access-date=26 March 2021 | archive-date=25 March 2021 | archive-url=https://web.archive.org/web/20210325082725/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da1c4de7-0e5b-4f72-97ec-7a8d368f085f | url-status=live }}</ref> Blitzima<ref>{{cite web | title=Blitzima EPAR | website=] | date=13 July 2017 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/blitzima | access-date=1 July 2024 | archive-date=9 September 2021 | archive-url=https://web.archive.org/web/20210909064129/https://www.ema.europa.eu/en/medicines/human/EPAR/blitzima | url-status=live }}</ref> Ituxredi,<ref name="Ituxredi EPAR" /><ref name="Ituxredi PI" /> Riabni,<ref name="Riabni FDA label" /> Rixathon,<ref>{{cite web | title=Rixathon EPAR | website=] | date=15 June 2017 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/rixathon | access-date=7 January 2024 | archive-date=9 September 2021 | archive-url=https://web.archive.org/web/20210909064148/https://www.ema.europa.eu/en/medicines/human/EPAR/rixathon | url-status=live }}</ref> Riximyo,<ref>{{cite web | title=Summary Basis of Decision (SBD) for Riximyo | website=] | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00494&lang=en | access-date=29 May 2022 | archive-date=30 May 2022 | archive-url=https://web.archive.org/web/20220530055258/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00494&lang=en | url-status=live }}</ref> Ruxience,<ref name="Ruxience FDA label" /> Truxima<ref name="Truxima FDA label" />

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="MabThera PI"> {{webarchive|date=30 November 2015|url=https://web.archive.org/web/20151130164406/https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropmabth10415}}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = /&nbsp;Schedule D<ref>{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=] | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024 | archive-date=25 March 2024 | archive-url=https://web.archive.org/web/20240325234307/https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | url-status=live }}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref name="MabThera SmPC">{{cite web | title=Mabthera 100 mg Concentrate for Solution for Infusion - Summary of Product Characteristics (SmPC) | website=(emc) | date=13 March 2021 | url=https://www.medicines.org.uk/emc/product/3801/smpc | access-date=26 March 2021 | archive-date=21 January 2022 | archive-url=https://web.archive.org/web/20220121012710/https://www.medicines.org.uk/emc/product/3801/smpc | url-status=live }}</ref><ref name="MabThera SC SmPC">{{cite web | title=Mabthera 1400 mg Solution for Subcutaneous Injection - Summary of Product Characteristics (SmPC) | website=(emc) | date=13 March 2021 | url=https://www.medicines.org.uk/emc/product/5333/smpc | access-date=26 March 2021}}</ref>
| legal_US = Rx-only | legal_US = Rx-only
| legal_US_comment = <ref name="Rituxan FDA label" /><ref name="Truxima FDA label" /><ref name="Ruxience FDA label" /><ref name="Riabni FDA label" />
| legal_status =
| legal_EU = Rx-only
| routes_of_administration = intravenous infusion only (never bolus or "push")
| legal_EU_comment = <ref name="MabThera EPAR">{{cite web | title=Mabthera EPAR | website=] | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/mabthera | access-date=8 September 2021 | archive-date=9 September 2021 | archive-url=https://web.archive.org/web/20210909063437/https://www.ema.europa.eu/en/medicines/human/EPAR/mabthera | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=Mabthera PI | website=Union Register of medicinal products | date=3 June 1998 | url=https://ec.europa.eu/health/documents/community-register/html/h067.htm | access-date=5 July 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = <!--For countries not listed above-->


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = 100% (IV) | bioavailability = 100% (IV)
| protein_bound = | protein_bound =
| metabolism = | metabolism =
| metabolites =
| onset =
| elimination_half-life = 30 to 400 hours (varies by dose and length of treatment) | elimination_half-life = 30 to 400 hours (varies by dose and length of treatment)
| duration_of_action =
| excretion = Uncertain: may undergo phagocytosis and catabolism in RES | excretion = Uncertain: may undergo phagocytosis and catabolism in RES


<!--Identifiers--> <!-- Identifiers -->
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = NA
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 174722-31-7 | CAS_number = 174722-31-7
| ATC_prefix = L01 | CAS_supplemental =
| ATC_suffix = XC02 | PubChem =
| ATC_supplemental = | IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| PubChem =
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00073 | DrugBank = DB00073
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4F4X42SYQ6 | UNII = 4F4X42SYQ6
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02994 | KEGG = D02994
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = <!-- blanked - oldvalue: 1201576 --> | ChEMBL = 1201576
| NIAID_ChemDB =
| C=6416 | H=9874 | N=1688 | O=1987 | S=44
| PDB_ligand =
| molecular_weight = 143859.7 g/mol

<!-- Chemical and physical data -->
| C=6416 | H=9874 | N=1688 | O=1987 | S=44
}} }}
'''Rituximab''', sold under the trade names '''Rituxan''' and '''MabThera''', is a ] ] against the protein ], which is primarily found on the surface of ]. Rituximab is used in the treatment of many ]s, ]s, ] and some ]s.


<!-- Definition and medical uses -->
==History==
'''Rituximab''', sold under the brand name '''Rituxan''' among others, is a ] medication used to treat certain ] and types of ].<ref name=AHFS2016/> It is used for ], ] (in children and adults, but not recommended in elderly patients), ], ], ], ], ] and ]-positive ]s.<ref name=AHFS2016/><ref>{{cite journal | vauthors = Tandan R, Hehir MK, Waheed W, Howard DB | title = Rituximab treatment of myasthenia gravis: A systematic review | journal = Muscle & Nerve | volume = 56 | issue = 2 | pages = 185–196 | date = August 2017 | pmid = 28164324 | doi = 10.1002/mus.25597 | s2cid = 19504332 }}</ref><ref>{{cite journal | vauthors = Singer O, McCune WJ | title = Update on maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis | journal = Current Opinion in Rheumatology | volume = 29 | issue = 3 | pages = 248–253 | date = May 2017 | pmid = 28306595 | doi = 10.1097/BOR.0000000000000382 | s2cid = 35805200 }}</ref><ref name=Doj2018>{{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 | volume = 7 | issue = 1 | pages = 28 | date = March 2018 | pmid = 29518976 | pmc = 5874754 | doi = 10.3390/pathogens7010028 | doi-access = free | title-link = doi }}</ref> It is given by slow ] (injected slowly through an IV line).<ref name=AHFS2016>{{cite web|title=Rituximab|url=https://www.drugs.com/monograph/rituximab.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-date=27 March 2016|archive-url=https://web.archive.org/web/20160327001117/http://www.drugs.com/monograph/rituximab.html}}</ref>
Rituximab was developed by ] (formed in 1986 by ] and ]) under the name '''IDEC-C2B8'''.<ref>, Fikes, Bradley J. ''San Diego Metropolitan,'' April 1999. Accessed June 20, 2008.</ref>


<!-- Side effects -->
Based on its safety and effectiveness in ]s,<ref>{{cite journal |author=Maloney DG, Grillo-López AJ, White CA, ''et al.'' |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 |year=1997 |month=September |pmid=9310469 |doi= |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=9310469}}</ref> rituximab was approved by the ] in 1997 to treat B-cell ]s resistant to other ] regimens.<ref>{{cite journal |author=Scott SD |title=Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma |journal=Cancer Pract |volume=6 |issue=3 |pages=195–7 |year=1998 |pmid=9652253 |doi= 10.1046/j.1523-5394.1998.006003195.x|url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1065-4704&date=1998&volume=6&issue=3&spage=195}}</ref> Rituximab, in combination with ] chemotherapy, is now a standard therapy in the initial treatment of ] and many other B-cell lymphomas.{{Citation needed|date=October 2010}} In 2010 it was approved by the ] for maintenance treatment after initial treatment of ].<ref>{{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 }}</ref>
The most common side effects with intravenous infusions are reactions related to the infusion (such as fever, chills and shivering) while most common serious side effects are infusion reactions, infections and heart-related problems.<ref name="MabThera EPAR" /> Similar side effects are seen when it is injected under the skin, with the exception of reactions around the injections site (pain, swelling and rash), which occur more frequently with the skin injections.<ref name="MabThera EPAR" />


Severe side effects include reactivation of ] in those previously infected, ], ], and death.<ref name=AHFS2016/><ref>{{cite web | title=FDA Drug Safety Communication: Boxed Warning and new recommendations to decrease risk of hepatitis B reactivation with the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab) | website=U.S. ] (FDA) | date=29 February 2016 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-boxed-warning-and-new-recommendations-decrease-risk-hepatitis-b | access-date=2 February 2020 | archive-date=28 April 2020 | archive-url=https://web.archive.org/web/20200428213737/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-boxed-warning-and-new-recommendations-decrease-risk-hepatitis-b | url-status=live }}</ref> It is unclear if use during ] is safe for the developing fetus or newborn baby.<ref name="Drugs.com pregnancy" /><ref name=AHFS2016/>
Rituximab is currently co-marketed by ] and ] in the U.S., by ] in Canada and the ], and by ] and Zenyaku Kogyo in Japan.


<!-- Mechanism -->
==Uses==
Rituximab is a ] ] against the protein ], which is primarily found on the surface of immune system ].<ref name=Bos2013/> When it binds to this protein it triggers cell death.<ref name=AHFS2016/>
Rituximab destroys both normal and malignant ] 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.


<!-- History society and culture -->
===Hematological neoplastic diseases===
Rituximab was approved for medical use in 1997.<ref name=Bos2013>{{cite book| vauthors = Bosch X, Ramos-Casals M, Khamashta MA |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|url-status=live|archive-url=https://web.archive.org/web/20171105200138/https://books.google.com/books?id=2l-4BAAAQBAJ&pg=PA4|archive-date=5 November 2017}}</ref> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> Rituxan is co-marketed by ] and ] in the US, by ] elsewhere except Japan, and co-marketed by ] and Zenyaku Kogyo in Japan.<ref name="Biogen PR 20100218">{{cite press release|url=https://investors.biogen.com/news-releases/news-release-details/fda-approves-rituxan-plus-chemotherapy-most-common-type-adult|title=FDA Approves Rituxan Plus Chemotherapy for the Most Common Type of Adult Leukemia|publisher=Biogen|date=18 February 2010|access-date=30 June 2021|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709182746/https://investors.biogen.com/news-releases/news-release-details/fda-approves-rituxan-plus-chemotherapy-most-common-type-adult|url-status=live}}</ref><ref>{{cite press release | title=FDA Approves Genentech's Rituxan (rituximab) in Children With Two Rare Blood Vessel Disorders | publisher=Genentech | via=Business Wire | date=27 September 2019 | url=https://www.businesswire.com/news/home/20190927005432/en/FDA-Approves-Genentech%E2%80%99s-Rituxan-rituximab-in-Children-With-Two-Rare-Blood-Vessel-Disorders | access-date=27 August 2024}}</ref>
Rituximab used to treat ] such as ]s and ]s.The use of rituximab in Hodgkin's lymphoma, including the lymphocyte predominant subtype has been reviewed recently.<ref>{{cite journal | author = 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}}</ref>


== Medical uses ==
In ], treatment with rituximab fails to deplete circulating CD20+ B or plasma cells, even after up to four cycles of treatment; in some patients, rituximab treatment increases the number of circulating CD20+ B cells.<ref></ref>


Rituximab is a chimeric monoclonal antibody targeted against CD20, a ] ] present on ]s. It acts by depleting normal as well as pathogenic B cells while sparing ]s and ]s, which do not express the CD20 surface antigen.<ref>{{cite journal | vauthors = De A, Ansari A, Sharma N, Sarda A | title = Shifting Focus in the Therapeutics of Immunobullous Disease | journal = Indian Journal of Dermatology | volume = 62 | issue = 3 | pages = 282–290 | date = 2017 | pmid = 28584371 | pmc = 5448263 |doi = 10.4103/ijd.IJD_199_17 | doi-access = free | title-link = doi }}</ref>
===Autoimmune diseases===
Rituximab has been shown to be an effective ] treatment in three randomised controlled trials and is now licensed for use in refractory rheumatoid disease.<ref>{{cite journal | author = 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}}</ref> In the United States, it has been FDA-approved for use in combination with ] (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-] therapy. In Europe, the licence 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.<ref>{{cite journal
| author = Tak PP, Kalden JR
| title = Advances in rheumatology: new targeted therapeutics
| journal = Arthritis Res Ther
| year = 2011
| volume = 13
| issue = Suppl 1
| pages = S5
| pmid = 21624184
| doi = 10.1186/1478-6354-13-S1-S5
| pmc = 3123966
}}</ref>


In the United States, rituximab is ] to treat:
There is some evidence for efficacy, but not necessarily ], in a range of other autoimmune diseases, and rituximab is widely used ] to treat difficult cases of ],<ref></ref> ] and autoimmune ]s.<ref name=NWU>{{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}}</ref> There are significant concerns about ] (PML) infection in SLE patients<ref>http://www.fda.gov/bbs/topics/NEWS/2006/NEW01532.html</ref> and other conditions.<ref name=NWU />


# ]<ref name="Rituxan FDA label" />
Other autoimmune diseases that have been treated with rituximab include ], ], ] (ITP),<ref>Braendstrup P, Bjerrum OW, Nielsen OJ, Jensen BA, Clausen NT, Hansen PB, Andersen I, Schmidt K, Andersen TM, Peterslund NA, Birgens HS, Plesner T, Pedersen BB, Hasselbalch HC. ''Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura.'' Am J Hematol 2005;78:275-80. PMID 15795920.</ref><ref>Patel V, Mihatov N, Cooper N, Stasi R, Cunningham-Rundles S, Bussel JB,''Long-term responses seen with rituximab in patients with ITP'', Community Oncology Vol. 4 No. 2, February 2007:107 </ref> ],<ref>Shanafelt, Tait D, MD; Madueme, Hans L, MD; Wold, Robert C, PharmD; Tefferi, Ayalew, MD ''Rituximab for Immune Cytopenia in Adults: Idiopathic Thrombocytopenic Purpura, Autoimmune Hemolytic Anemia, and Evans Syndrome'' Mayo Clinic Proc. 2003;78:1340-1346 </ref> vasculitis (for example ]), bullous skin disorders (for example ], ]), type 1 ], ], and ],<ref>{{cite journal |author=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}}</ref> and thyroid-associated ophthalmopathy.<ref>{{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}}</ref>
# ]<ref name="Rituxan FDA label" />
# ] having inadequate response to one or more ]s<ref name="Rituxan FDA label" />
# ] such as ] and ]<ref name="Rituxan FDA label" />
# moderate to severe ]<ref name="Rituxan FDA label" />
# in combination with chemotherapy for children (≥ 6 months to < 18 years) with previously untreated, advanced stage, CD20-positive ] (DLBCL), ] (BL), Burkitt-like lymphoma (BLL), or mature acute ] (B-AL).<ref name="Rituxan FDA label" /><ref name="FDA 20211203">{{cite web | title=FDA approves rituximab plus chemotherapy for pediatric cancer indications | website=U.S. Food and Drug Administration | date=3 December 2021 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rituximab-plus-chemotherapy-pediatric-cancer-indications | access-date=4 December 2021 | archive-date=3 December 2021 | archive-url=https://web.archive.org/web/20211203153512/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rituximab-plus-chemotherapy-pediatric-cancer-indications | url-status=live }} {{PD-notice}}</ref>


In the European Union, rituximab is indicated for the treatment of follicular lymphoma and diffuse large B cell non-Hodgkin's lymphoma (two types of non-Hodgkin's lymphoma, a blood cancer);<ref name="MabThera EPAR" /> chronic lymphocytic leukemia (CLL, another blood cancer affecting white blood cells);<ref name="MabThera EPAR" /> severe rheumatoid arthritis (an inflammatory condition of the joints);<ref name="MabThera EPAR" /> two inflammatory conditions of blood vessels known as granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA);<ref name="MabThera EPAR" /> moderate to severe pemphigus vulgaris, an autoimmune disease characterised by widespread blistering and erosion of the skin and mucous membranes (the linings of internal organs). 'Autoimmune' means that the disease is caused by the immune system (the body's natural defences) attacking the body's own cells.<ref name="MabThera EPAR" />
A new study from Norway suggests that rituximab can help patients with ].<ref name="pmid19566965">{{cite journal |author=Fluge O, Mella O |title=Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series |journal=BMC Neurology |volume=9 |pages=28 |year=2009 |month=July |pmid=19566965 |doi=10.1186/1471-2377-9-28 |url=http://www.biomedcentral.com/1471-2377/9/28 |pmc=2711959}}</ref> A clinical trial is completed.<ref></ref><ref></ref>


=== Blood cancers ===
===Anti-rejection treatment for organ transplants===
Rituximab is used to treat ] such as ]s and ]s, including non-Hodgkin's lymphoma, ], and nodular lymphocyte predominant Hodgkin's lymphoma.<ref>{{cite journal | vauthors = Saini KS, Azim HA, 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 Treatment Reviews | volume = 37 | issue = 5 | pages = 385–390 | date = August 2011 | pmid = 21183282 | doi = 10.1016/j.ctrv.2010.11.005 }}</ref><ref>{{cite journal | vauthors = Eichenauer DA, Engert A | title = Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management | journal = Hematology. American Society of Hematology. Education Program | volume = 2017 | issue = 1 | pages = 324–328 | date = December 2017 | pmid = 29222274 | pmc = 6142570 | doi = 10.1182/asheducation-2017.1.324 }}</ref> This also includes ], a type of non-Hodgkin lymphoma.<ref name=AHFS2016/> Rituximab in combination with ] human, sold under the brand names Mabthera SC<ref name="MabThera SC SmPC" /> and Rituxan Hycela,<ref name="Rituxan Hycela label" /> is used to treat ], ], and chronic lymphocytic leukemia.<ref name="Rituxan Hycela label">{{cite web|date=3 December 2019|title=Rituxan Hycela- rituximab and hyaluronidase injection, solution|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e5b7e82-f018-4eaf-ae78-d6145a906b20|access-date=2 February 2020|website=DailyMed|archive-date=27 March 2021|archive-url=https://web.archive.org/web/20210327083228/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e5b7e82-f018-4eaf-ae78-d6145a906b20|url-status=live}}</ref> It is used in combination with ] and ] to treat previously untreated and previously treated CD20-positive chronic lymphocytic leukemia.<ref name="Rituxan FDA label">{{cite web|date=6 November 2019|title=Rituxan- rituximab injection, solution|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b172773b-3905-4a1c-ad95-bab4b6126563|access-date=2 February 2020|website=DailyMed|archive-date=4 August 2020|archive-url=https://web.archive.org/web/20200804180021/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b172773b-3905-4a1c-ad95-bab4b6126563|url-status=live}}</ref>
Rituximab is now being used off-label in the management of ] 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.{{Fact|date=February 2011}}


=== Autoimmune diseases ===
==Mechanism==
The antibody binds to ]]. CD20 is widely expressed on B cells, from early pre-B cells to later in differentiation, but it is absent on terminally differentiated ]s. CD20 does not shed, modulate or internalise. Although the function of CD20 is unknown, it may play a role in ] influx across plasma membranes, maintaining intracellular Ca<sup>2+</sup> concentration and allowing activation of B cells.


Rituximab has been shown to be an effective ] treatment in three ] and is now licensed for use in ] rheumatoid disease.<ref>{{cite journal | vauthors = Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T | title = Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis | journal = The New England Journal of Medicine | volume = 350 | issue = 25 | pages = 2572–2581 | date = June 2004 | pmid = 15201414 | doi = 10.1056/NEJMoa032534 | doi-access = free | title-link = doi }}</ref> In the United States, it has been ] for use in combination with ] 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-] therapy. In the European Union, the license is slightly more restrictive: it is licensed for use in combination with methotrexate in patients with severe active RA who have had an inadequate response to one or more anti-TNF therapy.<ref>{{cite journal | vauthors = Tak PP, Kalden JR | title = Advances in rheumatology: new targeted therapeutics | journal = Arthritis Research & Therapy | volume = 13 | issue = Suppl 1 | pages = S5 | date = May 2011 | pmid = 21624184 | pmc = 3123966 | doi = 10.1186/1478-6354-13-S1-S5 | doi-access = free | title-link = doi }}</ref>
The exact mode of action of rituximab is unclear, but the following effects have been found:<ref>see e.g. T Shaw, J Quan, and M Totoritis, "", '''Ann Rheum Dis.''' 2003 November; 62(Suppl 2): ii55–ii59.</ref>

* The ] portion of rituximab mediates ] (ADCC) and ] (CDC).
There is some evidence for efficacy, but not necessarily ], in a range of other autoimmune diseases, and rituximab is widely used ] to treat difficult cases of ],<ref name=McGinley2017rev>{{cite journal | vauthors = McGinley MP, Moss BP, Cohen JA | title = Safety of monoclonal antibodies for the treatment of multiple sclerosis | journal = Expert Opinion on Drug Safety | volume = 16 | issue = 1 | pages = 89–100 | date = January 2017 | pmid = 27756172 | doi = 10.1080/14740338.2017.1250881 | s2cid = 36762194 }}</ref><ref>{{cite journal | vauthors = He D, Guo R, Zhang F, Zhang C, Dong S, Zhou H | title = Rituximab for relapsing-remitting multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD009130 | date = December 2013 | pmid = 24310855 | doi = 10.1002/14651858.CD009130.pub3 }}</ref> ], ] and autoimmune ]s.<ref name=NWU>{{cite web|url=http://www.northwestern.edu/newscenter/stories/2009/05/bennett.html|title=Popular Cancer Drug Linked to Often Fatal 'Brain Eating' Virus| vauthors = Paul M |date=20 May 2009|publisher=Northwestern University News and Information|access-date=22 May 2009|url-status=dead |archive-url=https://web.archive.org/web/20100529073721/http://www.northwestern.edu/newscenter/stories/2009/05/bennett.html|archive-date=29 May 2010}}</ref><ref>{{cite web | title=Popular Cancer Drug Linked To Often Fatal Brain Virus | website=ScienceDaily | date=9 May 2009 | url=https://www.sciencedaily.com/releases/2009/05/090518161158.htm | access-date=5 July 2024}}</ref> The most dangerous, although among the most rare, side effect is ] infection, which is usually fatal; however, only a very small number of cases have been recorded occurring in autoimmune diseases.<ref name=NWU /><ref>{{cite press release |url=https://www.fda.gov/bbs/topics/NEWS/2006/NEW01532.html |title=FDA Warns of Safety Concern Regarding Rituxan in New Patient Population |website=U.S. ] (FDA) |date=18 December 2006 |access-date=29 April 2013 |url-status=dead |archive-date=13 May 2009 |archive-url=https://web.archive.org/web/20090513023924/https://www.fda.gov/bbs/topics/NEWS/2006/NEW01532.html}}</ref>

Other autoimmune diseases that have been treated with rituximab include ], ], ] (TTP),<ref>{{cite journal | vauthors = Froissart A, Veyradier A, Hié M, Benhamou Y, Coppo P | title = Rituximab in autoimmune thrombotic thrombocytopenic purpura: A success story | journal = European Journal of Internal Medicine | volume = 26 | issue = 9 | pages = 659–665 | date = November 2015 | pmid = 26293834 | doi = 10.1016/j.ejim.2015.07.021 | doi-access = free | title-link = doi }}</ref> ] (ITP),<ref>{{cite journal | vauthors = Braendstrup P, Bjerrum OW, Nielsen OJ, Jensen BA, Clausen NT, Hansen PB, Andersen I, Schmidt K, Andersen TM, Peterslund NA, Birgens HS, Plesner T, Pedersen BB, Hasselbalch HC | title = Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura | journal = American Journal of Hematology | volume = 78 | issue = 4 | pages = 275–280 | date = April 2005 | pmid = 15795920 | doi = 10.1002/ajh.20276 | s2cid = 42218074 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = 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 | url-status = dead | archive-url = https://web.archive.org/web/20070929061010/http://www.communityoncology.net/journal/articles/0402107.pdf | archive-date = 29 September 2007 | access-date = 18 April 2007 | department=Correspondence }}</ref> ],<ref>{{cite journal | vauthors = Shanafelt TD, Madueme HL, Wolf RC, Tefferi A | title = Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome | journal = Mayo Clinic Proceedings | volume = 78 | issue = 11 | pages = 1340–1346 | date = November 2003 | pmid = 14601692 | doi = 10.4065/78.11.1340 }}</ref> vasculitis (e.g., ]), ] skin disorders (for example, ], ]—with very encouraging results of approximately 85% rapid recovery in pemphigus, according to a 2006 study),<ref>{{cite journal | vauthors = Ahmed AR, Spigelman Z, Cavacini LA, Posner MR | title = Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin | journal = The New England Journal of Medicine | volume = 355 | issue = 17 | pages = 1772–1779 | date = October 2006 | pmid = 17065638 | doi = 10.1056/nejmoa062930 | doi-access = free | title-link = doi }}</ref> type 1 ], ], ] and ](], ]),<ref>{{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 = Archives of Neurology | volume = 65 | issue = 11 | pages = 1443–1448 | date = November 2008 | pmid = 18779415 | doi = 10.1001/archneur.65.11.noc80069 | doi-access = free | title-link = doi }}</ref> ],<ref>{{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 |access-date=19 October 2011 |url-status=dead |archive-url=https://web.archive.org/web/20170822220531/http://www.ophthalmologyjournaloftheaao.com/article/S0161-6420(09)00548-X/abstract |archive-date=22 August 2017 }}</ref> ],<ref>{{cite journal |title=Immunomodulators and Rituximab in the Management of Autoimmune Pancreatitis |journal=Pancreapedia |date=11 June 2013 |doi=10.3998/panc.2013.20 | doi-access = free | title-link = doi | vauthors = Hart PA, Chari ST }}</ref> ] (OMS),<ref>{{cite journal | vauthors = Pranzatelli MR, Tate ED, Travelstead AL, Longee D | title = Immunologic and clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome | journal = Pediatrics | volume = 115 | issue = 1 | pages = e115–e119 | date = January 2005 | pmid = 15601813 | doi = 10.1542/peds.2004-0845 | doi-access = free | title-link = doi }}</ref> and ].<ref>{{cite journal | vauthors = Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari ST, Della-Torre E, Frulloni L, Goto H, Hart PA, Kamisawa T, Kawa S, Kawano M, Kim MH, Kodama Y, Kubota K, Lerch MM, Löhr M, Masaki Y, Matsui S, Mimori T, Nakamura S, Nakazawa T, Ohara H, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig TE, Yamamoto M, Zhang W, Chiba T, Stone JH | title = International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease | journal = Arthritis & Rheumatology | volume = 67 | issue = 7 | pages = 1688–1699 | date = July 2015 | pmid = 25809420 | doi = 10.1002/art.39132 | s2cid = 39750214 }}</ref> There is some evidence that it is ineffective in treating IgA-mediated autoimmune diseases.<ref>{{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 Dermatology | volume = 151 | issue = 6 | pages = 646–650 | date = June 2015 | pmid = 25901938 | doi = 10.1001/jamadermatol.2015.59 | doi-access = free | title-link = doi }}</ref>

== Adverse events ==

Serious adverse events, which can cause death and disability, include:<ref name="Rituxan FDA label" /><ref name=AHFS2016 />

* Severe ]
* ]
* ]
* ], causing ]
* Infections<ref>{{cite journal | vauthors = Kyriakidis I, Mantadakis E, Stiakaki E, Groll AH, Tragiannidis A | title = Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas | journal = Cancers | volume = 14 | issue = 20 | pages = 5022 | date = October 2022 | pmid = 36291806 | pmc = 9599435 | doi = 10.3390/cancers14205022 | doi-access = free | title-link = doi }}</ref>
** ] caused by ] reactivation<ref>{{cite journal | vauthors = Molloy ES, Calabrese LH | title = Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies | journal = Arthritis and Rheumatism | volume = 64 | issue = 9 | pages = 3043–3051 | date = September 2012 | pmid = 22422012 | doi = 10.1002/art.34468 }}</ref>
**] reactivation
** Other viral infections<ref>{{cite journal | vauthors = Grammatikos A, Donati M, Johnston SL, Gompels MM | title = Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies | journal = Frontiers in Immunology | volume = 12 | pages = 731643 | date = 30 August 2021 | pmid = 34527001 | pmc = 8435594 | doi = 10.3389/fimmu.2021.731643 | doi-access = free | title-link = doi }}</ref>
* Immune toxicity, with depletion of B cells in 70% to 80% of ] patients
* ] toxicity<ref>{{cite journal | vauthors = Burton C, Kaczmarski R, Jan-Mohamed R | title = Interstitial pneumonitis related to rituximab therapy | journal = The New England Journal of Medicine | volume = 348 | issue = 26 | pages = 2690–1; discussion 2690–1 | date = June 2003 | pmid = 12826649 | doi = 10.1056/NEJM200306263482619 }}</ref>
* ] and ]<ref>{{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=10 November 2006 |publisher=Roche Canada |url-status=dead |archive-url=https://web.archive.org/web/20140327221239/http://rochecanada.com/portal/servlet/staticfilesServlet?type=data&communityId=re753001&id=static%2Fattachedfile%2Fre7300002%2Fre77300002%2FAttachedFile_04801.pdf |archive-date=27 March 2014 }}</ref>
A concern with continuous rituximab treatment is the difficulty to induce a proper vaccine response.<ref>{{cite journal | vauthors = Oren S, Mandelboim M, Braun-Moscovici Y, Paran D, Ablin J, Litinsky I, Comaneshter D, Levartovsky D, Mendelson E, Azar R, Wigler I, Balbir-Gurman A, Caspi D, Elkayam O | title = Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response | journal = Annals of the Rheumatic Diseases | volume = 67 | issue = 7 | pages = 937–941 | date = July 2008 | pmid = 17981914 | doi = 10.1136/ard.2007.077461 | s2cid = 21878513 | doi-access = free | title-link = doi }}</ref>{{Unreliable medical source|date=October 2024|reason=primary source study}} This was brought into focus during the ], where persons with ] and rituximab treatment had higher risk of severe COVID-19.<ref>{{cite journal |vauthors=Spelman T, Forsberg L, McKay K, Glaser A, Hillert J |date=June 2022 |title=Increased rate of hospitalisation for COVID-19 among rituximab-treated multiple sclerosis patients: A study of the Swedish multiple sclerosis registry |journal=Multiple Sclerosis |volume=28 |issue=7 |pages=1051–1059 |doi=10.1177/13524585211026272 |pmid=34212816 |s2cid=235710318 | doi-access = free | title-link = doi }}</ref>{{Unreliable medical source|date=October 2024|reason=primary source study}}<ref>{{cite journal | vauthors = Reyes S, Ramsay M, Ladhani S, Amirthalingam G, Singh N, Cores C, Mathews J, Lambourne J, Marta M, Turner B, Gnanapavan S, Dobson R, Schmierer K, Giovannoni G | display-authors = 6 | title = Protecting people with multiple sclerosis through vaccination | journal = Practical Neurology | volume = 20 | issue = 6 | pages = 435–445 | date = December 2020 | pmid = 32632038 | doi = 10.1136/practneurol-2020-002527 | doi-access = free }}</ref> In persons previously treated with rituximab for multiple sclerosis, nine of ten patients who delayed re-dosing until B cell counts passed 40/μL developed protective levels of antibodies after vaccination with the ].<ref>{{cite journal | vauthors = Tolf A, Wiberg A, Müller M, Nazir FH, Pavlovic I, Laurén I, Mangsbo S, Burman J | title = Factors Associated With Serological Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Rituximab | journal = JAMA Network Open | volume = 5 | issue = 5 | pages = e2211497 | date = May 2022 | pmid = 35544139 | doi = 10.1001/jamanetworkopen.2022.11497 | pmc = 9096596 | s2cid = 248695128 }}</ref>{{Unreliable medical source|date=October 2024|reason=primary source study}}

== Mechanisms of action ==
]

]

The antibody binds to the cell surface protein ]. CD20 is widely expressed on B cells, from early pre-B cells to later in ], but it is absent on terminally differentiated ]s. Although the function of CD20 is unknown, it may play a role in ] influx across plasma membranes, maintaining intracellular Ca<sup>2+</sup> concentration and allowing activation of B cells.

Rituximab is relatively ineffective in elimination of cells with low CD20 cell-surface levels.<ref name="pmid32482755">{{cite journal | vauthors = Pavlasova G, Borsky M, Svobodova V, Oppelt J, Cerna K, Novotna J, Seda V, Fojtova M, Fajkus J, Brychtova Y, Doubek M, Pospisilova S, Mayer J, Mraz M | title = Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels | journal = Leukemia | volume = 32 | issue = 9 | pages = 2028–2031 | date = September 2018 | pmid = 30030508 | doi = 10.1038/s41375-018-0211-0 | doi-access = free | title-link = doi }}</ref> It 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.<ref name="pmid23613524">{{cite journal | vauthors = Rudnicka D, Oszmiana A, Finch DK, Strickland I, Schofield DJ, Lowe DC, Sleeman MA, Davis DM | 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 | date = June 2013 | pmid = 23613524 | doi = 10.1182/blood-2013-02-482570 | doi-access = free | title-link = doi }}</ref>

The following effects have been found:<ref>{{cite journal | vauthors = Shaw T, Quan J, Totoritis MC | title = B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience | journal = Annals of the Rheumatic Diseases | volume = 62 | issue = Suppl 2 | pages = ii55–ii59 | date = November 2003 | pmid = 14532151 | pmc = 1766758 | doi = 10.1136/ard.62.suppl_2.ii55 }}</ref>

* The ] portion of rituximab mediates ] (ADCC) and ] (CDC).<ref name="pmid34438120">{{cite journal | vauthors = Borsky M, Hrabcakova V, Novotna J, Brychtova Y, Doubek M, Panovska A, Muller P, Mayer J, Trbusek M, Mraz M | title = Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion | journal = Leukemia Research | volume = 111 | pages = 106684 | date = December 2021 | pmid = 34438120 | doi = 10.1016/j.leukres.2021.106684 }}</ref>
* Rituximab has a general regulatory effect on the ]. * Rituximab has a general regulatory effect on the ].
* Preferential elimination of malignant B cells with high CD20 levels and high BCR signaling propensity, especially in chronic lymphocytic leukemia (CLL).<ref name="pmid32482755" />
* It increases ] and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen). * It increases ] and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen).
* It elicits shedding of ]. * It elicits shedding of ].
* It downregulates the ]. * It downregulates the ].
* It induces ] of CD20+ cells. * It induces ] of CD20+ cells.
* Rituximab also induces a release of some chronic lymphocytic leukemia cells from immune niches, which might make them more sensitive to chemotherapy used in combination with an anti-CD20 antibody.<ref name="pmid34438120" />


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 ]s. 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 ]s.


Rituximab binds to ]s 170-173 and 182-185 on CD20, which are physically close to each other as a result of a ] between amino acids 167 and 183.<ref>{{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}}</ref> Rituximab binds to ]s 170–173 and 182–185 on CD20, which are physically close to each other as a result of a ] between amino acids 167 and 183.<ref>{{cite journal | vauthors = 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 | date = September 2006 | pmid = 16705086 | doi = 10.1182/blood-2006-04-014639 | doi-access = free | title-link = doi }}</ref>


==Adverse events== == History ==
Rituximab was developed by ] under the name IDEC-C2B8. The US patent for the drug was issued in 1998 and expired in 2015.<ref name=patentNPriceData>{{cite web|url=https://go.drugbank.com/drugs/DB00073|archiveurl=https://web.archive.org/web/20140105002750/http://www.drugbank.ca/drugs/DB00073|url-status=dead|title=Rituximab|archive-date=5 January 2014|website=go.drugbank.com|access-date=14 March 2023}}</ref>
Serious adverse events, which can cause ] and ], include:<ref name="titleGenentech: Products - Product Information - Immunology - Rituxan RA Full Prescribing Information">{{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 |format= |work=}}</ref>
*Severe infusion reactions
* ]
*], causing ]
*Infections
**] reactivation
**Other viral infections
**] (PML)
*Immune toxicity, with depletion of B cells in 70% to 80% of ] patients
*] toxicity<ref>{{cite journal |author=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}}</ref>


Based on its safety and effectiveness in ]s,<ref>{{cite journal | vauthors = Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R | 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 = 2188–2195 | date = September 1997 | pmid = 9310469 | doi = 10.1182/blood.V90.6.2188 | doi-access = free | title-link = doi }}</ref> rituximab was approved by the US ] (FDA) in 1997 to treat B-cell ]s resistant to other ] regimens.<ref name="Rituximab Product Approval">{{cite web | title=Rituximab Product Approval Information | website=U.S. ] (FDA) | date=20 February 2009 | url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm093345.htm | archive-url=http://web.archive.org/web/20170210011738/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm093345.htm | archive-date=10 February 2017 | url-status=dead }}</ref><ref>{{cite journal | vauthors = Scott SD | title = Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma | journal = Cancer Practice | volume = 6 | issue = 3 | pages = 195–197 | year = 1998 | pmid = 9652253 | doi = 10.1046/j.1523-5394.1998.006003195.x }}</ref> Rituximab, in combination with ], is superior to CHOP alone in the treatment of ] and many other B-cell lymphomas.<ref>''Harrison's Principles of Internal Medicine'', Longo et al. ''McGraw Hill Medical'' 2011 page 931</ref> In 2010, it was authorized by the ] for maintenance treatment after initial treatment of ].<ref>{{cite news |url=https://www.genengnews.com/news/roche-gets-ec-nod-for-follicular-lymphoma-maintenance-therapy/ |title=Roche Gets EC Nod for Follicular Lymphoma Maintenance Therapy |date=29 October 2010 |url-status=live |archive-url=https://web.archive.org/web/20101031202519/http://www.genengnews.com/gen-news-highlights/roche-gets-ec-nod-for-follicular-lymphoma-maintenance-therapy/81244149/ |archive-date=31 October 2010 }}</ref>
A small number of patients with ] have died in the context of being treated with rituximab.<ref name="urlRituximab (marketed as Rituxan) Information">{{cite web |url=http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109106.htm |title=Rituximab (marketed as Rituxan) Information |work= |accessdate=15 November 2009}}</ref> In some cases, reactivation of latent ] (a common virus that can cause ]) occurred in the brains of these patients. There has also been at least one case of a patient with ] who developed PML in the context of treatment with rituximab.<ref name="urlRituximab, RA and PML">{{cite web |url=http://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%209411700.pdf |title=Rituximab, RA and PML |format= |work= |accessdate=2008-09-14}}</ref> JC virus reactivation (resulting in PML) in an immunosuppressed person commonly results in death or severe brain damage.


It is on the ].<ref name="WHO23rd" />
Rituximab has been reported as a possible cofactor in a chronic ] infection in a person with lymphoma. Hepatitis E infection is normally an ] infection, suggesting the drug in combination with lymphoma may have weakened the body's immune response to the virus.<ref name="urlChronic Hepatitis After Hepatitis E Virus Infection in a Patient With Non-Hodgkin Lymphoma Taking Rituximab">{{cite web
|url=http://www.annals.org/cgi/reprint/150/6/430-a.pdf |title=Chronic Hepatitis After Hepatitis E Virus Infection in a Patient With Non-Hodgkin Lymphoma Taking Rituximab |format= |work= |accessdate=2008-09-14}}</ref>


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).<ref>{{cite web | vauthors = Stanton D |url=https://www.biopharma-reporter.com/Article/2016/06/01/EU-approves-indication-for-subcutaneous-form-of-Roche-s-MabThera |title=EU approves second indication for subcutaneous form of Roche's rituximab |access-date=9 June 2016 |url-status=live |archive-url=https://web.archive.org/web/20160607225341/http://www.biopharma-reporter.com/Bio-Developments/EU-approves-indication-for-subcutaneous-form-of-Roche-s-MabThera |archive-date=7 June 2016 | website=BioPharma-Reporter | date=31 May 2016 }}</ref>
== Other anti-CD20 monoclonals ==
The efficacy and success of Rituximab has led to some other anti-CD20 monoclonal antibodies being developed:
* ], humanized (90%-95% human) B cell-depleting agent.
* ] (HuMax-CD20) a fully human B cell-depleting agent.<ref name="titleGenmab.com / HuMax-CD20 (ofatumumab)">{{cite web |url=http://www.genmab.com/ScienceAndResearch/ProductsinDevelopment/HuMax-CD20.aspx |title=Genmab.com / HuMax-CD20 (ofatumumab) |accessdate=2007-12-03 |format= |work= |archiveurl = http://web.archive.org/web/20070911144653/http://www.genmab.com/ScienceAndResearch/ProductsinDevelopment/HuMax-CD20.aspx <!-- Bot retrieved archive --> |archivedate = 2007-09-11}}</ref>
* Third-generation anti-CD20s have a glycoengineered Fc fragment (Fc)<ref name="titleFc-structure">{{cite web |url=http://www.healthvalue.net/Fc-structure.html |title=Fc-structure |accessdate=2007-12-03 |work=}}</ref> with enhanced binding to Fc gamma receptors, which increase ADCC (]).<ref name="titleMonoclonal antibodies targeting cancer: 'magic bullets' or just the trigger?">{{cite journal |title=Monoclonal antibodies targeting cancer: 'magic bullets' or just the trigger? |format= |work= |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}}</ref> Modifications in the ]<ref name="titlemonoclonal domains">{{cite web |url=http://www.healthvalue.net/monoclonaldomainsengl.html |title=monoclonal domains |accessdate=2007-12-03 |work=}}</ref> can enhance apoptosis.


In June 2017, the US FDA granted regular approval to the combination of rituximab and hyaluronidase human (brand name Rituxan Hycela) for adults with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.<ref name="FDA 20170622">{{cite web | title=FDA approves rituximab plus hyaluronidase combination for Treatment of FL, DLBCL and CLL | website=U.S. ] (FDA) | date=22 June 2017 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rituximab-plus-hyaluronidase-combination-treatment-fl-dlbcl-and-cll | access-date=5 July 2024}} {{PD-notice}}</ref> The combination is not indicated for the treatment of non-malignant conditions.<ref name="Rituxan Hycela label" /><ref name="FDA 20170622" /> The combination was approved based on clinical studies SABRINA/NCT01200758 and MabEase/NCT01649856.<ref name="Rituxan Hycela label" />
The added value of a humanized molecule in oncology, compared to the original design, has not been demonstrated to this date.{{Citation needed|date=October 2010}}


In September 2019, the US FDA approved rituximab injection to treat granulomatosis with polyangiitis and microscopic polyangiitis in children two years of age and older in combination with glucocorticoids (steroid hormones).<ref name="FDA PR 20190927" /> It is the first approved treatment for children with these rare vasculitis diseases, in which a person's small blood vessels become inflamed, reducing the amount of blood that can flow through them.<ref name="FDA PR 20190927" /> This can cause serious problems and damage to organs, most notably the lungs and the kidneys.<ref name="FDA PR 20190927" /> It also can impact the sinuses and skin.<ref name="FDA PR 20190927">{{cite press release | title=FDA approves first treatment for children with rare diseases that cause inflammation of small blood vessels | website=U.S. ] (FDA) | date=27 September 2019 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-children-rare-diseases-cause-inflammation-small-blood-vessels | access-date=5 July 2024}} {{PD-notice}}</ref> Rituximab was approved by the FDA to treat adults with granulomatosis with polyangiitis and microscopic polyangiitis in 2011.<ref name="FDA PR 20190927" />
Another approach to B cell diseases is to block the interaction of B cell survival or growth factors with their receptors on B cells. The monoclonal antibody ] and ] are examples of such an approach.


In December 2021, the US FDA approved rituximab in combination with chemotherapy for children aged 6 months to 18 years with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia.<ref name="FDA 20211203" /><ref name="FDA DISCO 20211217">{{cite web | title=FDA D.I.S.C.O. Burst Edition: FDA approvals of Rituxan (rituximab) plus chemotherapy for pediatric cancer indications, and Keytruda (pembrolizumab) for adjuvant treatment of Stage IIB or IIC melanoma | website=U.S. ] (FDA) | date=2 December 2021 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approvals-rituxan-rituximab-plus-chemotherapy-pediatric-cancer | access-date=5 July 2024}} {{PD-notice}}</ref> Efficacy was evaluated in Inter-B-NHL Ritux 2010, a global multicenter, open-label, randomized 1:1 trial of participants six months in age or older with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or B-cell acute leukemia.<ref name="FDA DISCO 20211217" /> Advanced stage was defined as stage III with elevated lactose dehydrogenase level (lactose dehydrogenase greater than twice the institutional upper limit of normal values) or stage IV B-cell non-Hodgkin's lymphoma or B-cell acute leukemia.<ref name="FDA DISCO 20211217" /> Participants were randomized to Lymphome Malin B chemotherapy that consisted of corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicin, etoposide, and triple drug (methotrexate/cytarabine/corticosteroid) intrathecal therapy alone or in combination with rituximab or non-US licensed rituximab, administered as six infusions of rituximab IV at a dose of 375 mg/m2 as per the Lymphome Malin B scheme.<ref name="FDA DISCO 20211217" />
==References==
{{reflist|2}}


== Society and culture ==
==External links==
* Official website for use against lymphoma
* Official website for use against rheumatoid arthritis (for non-US physicians and scientific media only)
* Official website (for US residents only)
* from the US ]
*


=== Legal status ===
{{Extracellular chemotherapeutic agents}}
Rituximab was approved for medical use in the United States in November 1997.<ref name="Rituxan FDA label" /><ref name="Rituximab Product Approval" />

==== Biosimilars ====
]s are approved in the United States, India, the European Union, Switzerland, Japan, and Australia.{{cn|date=August 2024}} The US FDA approved rituximab-abbs (Truxima) in 2018,<ref name="Truxima FDA label" /><ref name="FDA PR 20181128" /><ref name="FDA Truxima" /> rituximab-pvvr (Ruxience) in 2019,<ref name="Ruxience FDA label" /> and rituximab-arrx (Riabni) in 2020.<ref name="Riabni FDA label" />

In July 2024, the ] of the ] adopted a positive opinion, recommending the granting of marketing authorization to ] for their rituximab biosimilar Ituxredi, intended for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis and pemphigus vulgaris.<ref name="Ituxredi EPAR">{{cite web |date=25 July 2024 |title=Ituxredi EPAR |url=https://www.ema.europa.eu/en/medicines/human/EPAR/ituxredi |access-date=27 July 2024 |website=European Medicines Agency}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Ituxredi was authorized for medical use in the European Union in September 2024.<ref name="Ituxredi EPAR" /><ref name="Ituxredi PI">{{cite web | title=Ituxredi Product information | website=Union Register of medicinal products | date=23 September 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1861.htm | access-date=24 September 2024}}</ref> Dr Reddy's Rituximab biosimilar Reditux was approved in India in 2007.<ref>{{Cite web |date=2018-03-13 |title=Rituximab Biosimilar to Launch in Turkish Market |url=https://www.centerforbiosimilars.com/view/rituximab-biosimilar-to-launch-in-turkish-market |access-date=2024-10-24 |website=Center for Biosimilars |language=en}}</ref>

=== Economics ===
In 2014, Genentech reclassified Rituxan as a ], a class of drugs that are only available through specialty distributors in the US.<ref name="Time_2014">{{cite magazine |date=27 October 2014 |title=Hospitals Furious at Cancer-Drug Price Hikes |url=https://time.com/3541484/cancer-drug-price-hikes/ |url-status=live |archive-url=https://web.archive.org/web/20151020062334/http://time.com/3541484/cancer-drug-price-hikes/ |archive-date=20 October 2015 |access-date=26 October 2015 |magazine=Time |vauthors=Saporito B}}</ref> Because wholesalers discounts and rebates no longer apply, hospitals would pay more.<ref name="Time_2014" />

Patents on rituximab have expired in the European Union<ref>{{cite web |date=24 July 1992 |title=Recombinant antibodies for human therapy |url=https://patents.google.com/patent/EP0605442A4/en |access-date=27 July 2024 |website=Google Patents}}</ref><ref>{{cite web |date=9 November 1999 |title=Chimeric anti-CD20 antibody, rituxan, for use in the treatment of chronic lymphocytic leukemia |url=https://patents.google.com/patent/EP1616572B1/en |access-date=27 July 2024 |website=Google Patents}}</ref><ref>{{cite journal |vauthors=Storz U |date=2014 |title=Rituximab: how approval history is reflected by a corresponding patent filing strategy |journal=mAbs |volume=6 |issue=4 |pages=820–37 |doi=10.4161/mabs.29105 |pmc=4171018 |pmid=24866199}}</ref> and in the United States.<ref>{{cite web |date=9 November 1999 |title=Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-CD20 antibody |url=https://patents.google.com/patent/US7682612B1/en |access-date=27 July 2024 |website=Google Patents}}</ref><ref>{{cite web |date=31 May 2013 |title=Methods related to rituximab |url=https://patents.google.com/patent/US20150141620A1/en |access-date=27 July 2024 |website=Google Patents}}</ref><ref>{{cite web | vauthors = Inserro A |date=25 March 2019 |title=Roche Settles With Pfizer Over Rituximab Patent |url=https://www.centerforbiosimilars.com/view/roche-settles-with-pfizer-over-rituximab-patent |access-date=27 July 2024 |website=Center for Biosimilars}}</ref> ]s were approved in the United States, India, the European Union, Switzerland, Japan, and Australia. The US FDA approved rituximab-abbs (Truxima) in 2018,<ref name="Truxima FDA label" /><ref name="FDA PR 20181128">{{cite press release|url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-treatment-adult-patients-non-hodgkins-lymphoma|title=FDA approves first biosimilar for treatment of adult patients with non-Hodgkin's lymphoma|date=28 November 2018|website=U.S. ] (FDA)|access-date=11 November 2019|archive-date=15 December 2019|archive-url=https://web.archive.org/web/20191215164843/https://www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-treatment-adult-patients-non-hodgkins-lymphoma|url-status=live}}</ref><ref name="FDA Truxima">{{cite web | title=FDA approves Truxima as biosimilar to Rituxan for non-Hodgkin's lympho | website=U.S. ] (FDA) | date=28 November 2018 | url=https://www.fda.gov/drugs/fda-approves-truxima-biosimilar-rituxan-non-hodgkins-lymphoma | access-date=5 July 2024}}</ref> rituximab-pvvr (Ruxience) in 2019,<ref name="Ruxience FDA label" /> and rituximab-arrx (Riabni) in 2020.<ref name="Riabni FDA label" /><ref name="GABI">{{cite web|url=https://gabionline.net/biosimilars/general/Biosimilars-of-rituximab |title=Biosimilars of Rituximab|publisher=Generics and Biosimilars Initiative|archive-url=https://web.archive.org/web/20240224193418/https://gabionline.net/biosimilars/general/Biosimilars-of-rituximab|archive-date=24 February 2024|url-status=live|access-date=29 April 2017|date=14 April 2017}}</ref><ref>{{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|vauthors=Lahiri D, Osterman C|date=2 November 2018|access-date=3 November 2018|publisher=Reuters|archive-date=3 November 2018|archive-url=https://web.archive.org/web/20181103034312/https://www.reuters.com/article/us-novartis-rituximab/novartis-abandons-effort-for-u-s-approval-of-biosimilar-rituximab-idUSKCN1N72NA|url-status=live}}</ref> Truxima and Riabni are approximately $3600 per 500&nbsp;mg, wholesale - 10% less than Rituxan, while Ruxience is 24% less than Rituxan.<ref>{{Cite web |date=4 May 2020 |title=Teva, Celltrion Maintain Slender Discount to Rituxan |url=https://www.centerforbiosimilars.com/view/teva-celltrion-maintain-slender-discount-to-rituxan |url-status=live |archive-url=https://web.archive.org/web/20240330194608/https://www.centerforbiosimilars.com/view/teva-celltrion-maintain-slender-discount-to-rituxan |archive-date=30 March 2024 |access-date=30 March 2024 |website=Center for Biosimilars}}</ref><ref name="Center4Biosimilars">{{cite web |date=17 December 2020 |title=Amgen Rituximab Biosimilar Gains FDA Approval |url=https://www.centerforbiosimilars.com/view/fda-approves-rituximab-biosimilar-from-amgen |url-status=live |archive-url=https://web.archive.org/web/20210423043501/https://www.centerforbiosimilars.com/view/fda-approves-rituximab-biosimilar-from-amgen |archive-date=23 April 2021 |access-date=23 April 2021 |website=The Center For Biosimilars |quote=The pharmaceutical company said Riabni will be marketed at a discount to the reference product of 23.7% below wholesale acquisition cost (WAC), or a WAC of $716.80 per 100 mg and $3584 per 500 mg single-dose vial. These costs are 15.2% less than the WAC for the biosimilar rituximab Truxima, Amgen said. The company added that Riabni's average sales price will be 16.7% below the current average for Rituxan.}}</ref> Dr Reddy's rituximab ''ituxredi'', available in India, retails for about 1/6 the price.<ref>{{cite news |title=Dr Reddy’s launches half-price version of MabThera - PharmaTimes |url=https://pharmatimes.com/news/dr_reddys_launches_half-price_version_of_mabthera_989813/ |access-date=19 November 2024 |work=pharmatimes.com |date=3 May 2007}}</ref>

==== Tailored-dosing ====
Tailored-dose rituximab is more cost-effective than fixed-dose. It is both more effective and less expensive.<ref>{{cite journal | vauthors = Contreras K, Orozco V, Puche E, González CA, García-Padilla P, Rodríguez MP, Rosselli D | title = Cost-Effectiveness of Rituximab (Fixed Schedule vs Tailored Dose) Compared With Azathioprine Maintenance Therapy in Adults With Generalized Antineutrophil Cytoplasm Antibody-Associated Vasculitis in Colombia | journal = Value in Health Regional Issues | volume = 28 | pages = 98–104 | date = March 2022 | pmid = 34922060 | doi = 10.1016/j.vhri.2021.08.002 }}</ref><ref>{{cite journal | vauthors = Romero G, Ticchioni M, Cohen M, Rosenthal-Allieri MA, Mondot L, Lebrun Frenay C | title = Neuromyelitis optica: Contribution of therapeutic responses markers monitoring in patients given rituximab | journal = Revue Neurologique | volume = 172 | issue = 3 | pages = 220–224 | date = March 2016 | pmid = 26915311 | doi = 10.1016/j.neurol.2015.12.004 }}</ref>

==Research==
Rituximab has been reported as a possible cofactor in a chronic ] infection in a person with lymphoma. Hepatitis E infection is normally an ] infection, suggesting the drug in combination with lymphoma may have weakened the body's immune response to the virus.<ref>{{cite journal | vauthors = Kriston L, Härter M, Hölzel L | title = Challenges in reporting meta-analyses of diagnostic accuracy studies | journal = Annals of Internal Medicine | volume = 150 | issue = 6 | pages = 430 | date = March 2009 | pmid = 19293085 | doi = 10.7326/0003-4819-150-6-200903170-00025 | department=Letters }}</ref>

===Myalgic encephalomyelitis/chronic fatigue syndrome===
In 2009, a patient receiving methotrexate-induced B-cell depletion for cancer treatment, experienced a transient remittal of their ] (ME/CFS) symptoms. While initial trials using Rituximab were promising, a phase 3 trial published in 2019 did not find an association between Rituximab treatment and improvements in ME/CFS.<ref name=":0">{{cite journal | vauthors = Fluge Ø, Rekeland IG, Lien K, Thürmer H, Borchgrevink PC, Schäfer C, Sørland K, Aßmus J, Ktoridou-Valen I, Herder I, Gotaas ME, Kvammen Ø, Baranowska KA, Bohnen LM, Martinsen SS, Lonar AE, Solvang AH, Gya AE, Bruland O, Risa K, Alme K, Dahl O, Mella O | title = B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial | journal = Annals of Internal Medicine | volume = 170 | issue = 9 | pages = 585–593 | date = May 2019 | pmid = 30934066 | doi = 10.7326/M18-1451 | s2cid = 91186383 }}</ref><ref>{{cite journal | vauthors = Seton KA, Espejo-Oltra JA, Giménez-Orenga K, Haagmans R, Ramadan DJ, Mehlsen J | title = Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives | journal = Journal of Clinical Medicine | volume = 13 | issue = 2 | page = 325 | date = January 2024 | pmid = 38256459 | pmc = 10816159 | doi = 10.3390/jcm13020325 | collaboration = European ME Research Group for Early Career Researchers (Young EMERG) | doi-access = free }}</ref>

===Intrathecal===

For CNS diseases, rituximab could be administered ]ly and this possibility is under study.<ref>{{cite journal | vauthors = Bonnan M, Ferrari S, Bertandeau E, Demasles S, Krim E, Miquel M, Barroso B | title = Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials | journal = Current Drug Targets | volume = 15 | issue = 13 | pages = 1205–1214 | date = 2014 | pmid = 25355180 | doi = 10.2174/1389450115666141029234644 }}</ref>

=== Other anti-CD20 monoclonals ===

The efficacy and success of rituximab has led to some other anti-CD20 monoclonal antibodies being developed:

* ], humanized (90%-95% human) B cell-depleting agent.
* ] (HuMax-CD20) a fully human B cell-depleting agent.<ref name="titleGenmab.com / HuMax-CD20 (ofatumumab)">{{cite web |url=http://www.genmab.com/ScienceAndResearch/ProductsinDevelopment/HuMax-CD20.aspx |title=Genmab.com / HuMax-CD20 (ofatumumab) |access-date=3 December 2007 |archive-url = https://web.archive.org/web/20070911144653/http://www.genmab.com/ScienceAndResearch/ProductsinDevelopment/HuMax-CD20.aspx <!-- Bot retrieved archive --> |archive-date = 11 September 2007}}</ref>
* Third-generation anti-CD20s such as ] have a glycoengineered ] (Fc)<ref name="titleFc-structure">{{cite web |url=http://www.healthvalue.net/Fc-structure.html |title=Fc-structure |access-date=3 December 2007 |url-status=live |archive-url=https://web.archive.org/web/20071110011928/http://www.healthvalue.net/Fc-structure.html |archive-date=10 November 2007 }}</ref> with enhanced binding to ]s, which increase ADCC (]).<ref name="titleMonoclonal antibodies targeting cancer: 'magic bullets' or just the trigger?">{{cite journal | vauthors = Eccles SA | title = Monoclonal antibodies targeting cancer: 'magic bullets' or just the trigger? | journal = Breast Cancer Research | volume = 3 | issue = 2 | pages = 86–90 | year = 2001 | pmid = 11250751 | pmc = 138676 | doi = 10.1186/bcr276 | doi-access = free | title-link = doi }}</ref> This strategy for enhancing a monoclonal antibody's ability to induce ADCC takes advantage of the fact that the displayed Fc glycan controls the antibody's affinity for Fc receptors.<ref>{{cite journal | vauthors = Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB | title = Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review | journal = Journal of Autoimmunity | volume = 57 | issue = 6 | pages = 1–13 | date = February 2015 | pmid = 25578468 | pmc = 4340844 | doi = 10.1016/j.jaut.2014.12.002 }}</ref>

== References ==
{{reflist}}

== Further reading ==
* {{cite report | title=Non-Hodgkin's lymphoma: rituximab subcutaneous injection | publisher=NICE | date=September 2014 | url=https://www.nice.org.uk/advice/esnm46/chapter/full-evidence-summary }}
* {{cite journal | vauthors = Salles G, Barrett M, Foà R, Maurer J, O'Brien S, Valente N, Wenger M, Maloney DG | title = Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience | journal = Advances in Therapy | volume = 34 | issue = 10 | pages = 2232–2273 | date = October 2017 | pmid = 28983798 | pmc = 5656728 | doi = 10.1007/s12325-017-0612-x }}
* {{cite journal | vauthors = Smith MR | title = Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance | journal = Oncogene | volume = 22 | issue = 47 | pages = 7359–68 | date = October 2003 | pmid = 14576843 | doi = 10.1038/sj.onc.1206939 }}

== External links ==
* {{cite web | title=Discovery – Development of Rituximab | website=National Cancer Institute | date=7 March 2014 | url=https://www.cancer.gov/research/progress/discovery/blood-cancer }}

{{Targeted cancer therapeutic agents}}
{{Monoclonals for tumors}} {{Monoclonals for tumors}}
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Rituximab: Difference between revisions Add topic