Chemistry:Rituximab

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Short description: Biopharmaceutical drug
Rituximab
Rituximab.png
Monoclonal antibody
TypeWhole antibody
SourceChimeric (mouse/human)
TargetCD20
Clinical data
Trade namesRituxan, Mabthera, Mabthera SC, others
AHFS/Drugs.comMonograph
MedlinePlusa607038
License data
Pregnancy
category
Routes of
administration		Intravenous
Drug classMonoclonal antibody
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability100% (IV)
Elimination half-life30 to 400 hours (varies by dose and length of treatment)
ExcretionUncertain: may undergo phagocytosis and catabolism in RES
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6416H9874N1688O1987S44
Molar mass143860.04 g·mol−1
 ☒N☑Y (what is this?)  (verify)

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer.[13] It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric patients), rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers.[13][14][15][16] It is given by slow intravenous infusion (injected slowly through an IV line).[13] Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza (F.K.A. Tuxella), Rixathon, Ruxience, and Truxima.[17][18]

Common side effects which often occur within two hours of the medication being given include rash, itchiness, low blood pressure, and shortness of breath. Infections are also common.[13]

Severe side effects include reactivation of hepatitis B in those previously infected, progressive multifocal leukoencephalopathy, toxic epidermal necrolysis, and death.[13][19] It is unclear if use during pregnancy is safe for the developing fetus or newborn baby,[1][13] but it is not proven harmful.

Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells.[20] When it binds to this protein it triggers cell death.[13]

Rituximab was approved for medical use in 1997.[20] It is on the World Health Organization's List of Essential Medicines.[21] Rituximab is 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.[22]

Medical uses

Rituximab is a chimeric monoclonal antibody targeted against CD20 which is a surface antigen present on B cells. Therefore, it acts by depleting normal as well as pathogenic B cells while sparing plasma cells and hematopoietic stem cells as they do not express the CD20 surface antigen.[23]

In the United States, rituximab is indicated to treat:

  1. non-Hodgkin lymphoma (NHL)[6]
  2. chronic lymphocytic leukemia (CLL)[6]
  3. rheumatoid arthritis having inadequate response to one or more TNF inhibitors[6]
  4. vasculitis such as granulomatosis with polyangiitis and microscopic polyangiitis[6]
  5. moderate to severe pemphigus vulgaris[6]
  6. in combination with chemotherapy for children (≥6 months to <18 years) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL).[24]

Blood cancers

Rituximab is used to treat cancers of the white blood system such as leukemias and lymphomas, including non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and nodular lymphocyte predominant Hodgkin's lymphoma.[25][26] This also includes Waldenström's macroglobulinemia, a type of NHL.[13] Rituximab in combination with hyaluronidase human, sold under the brand names MabThera SC and Rituxan Hycela,[27] is used to treat follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.[27] It is used in combination with fludarabine and cyclophosphamide to treat previously untreated and previously treated CD20-positive chronic lymphocytic leukemia.[6]

Autoimmune diseases

Rituximab 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.[28] 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 the European Union, 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.[29]

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,[30][31] systemic lupus erythematosus, chronic inflammatory demyelinating polyneuropathy and autoimmune anemias.[32] 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.[32][33]

Other autoimmune diseases that have been treated with rituximab include autoimmune hemolytic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura (TTP),[34] idiopathic thrombocytopenic purpura (ITP),[35][36] Evans syndrome,[37] 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),[38] type 1 diabetes mellitus, Sjögren syndrome, anti-NMDA receptor encephalitis and Devic's disease(Anti-AQP4 disease, MOG antibody disease),[39] Graves' ophthalmopathy,[40] autoimmune pancreatitis,[41] Opsoclonus myoclonus syndrome (OMS),[42] and IgG4-related disease.[43] There is some evidence that it is ineffective in treating IgA-mediated autoimmune diseases.[44]

Adverse events

Serious adverse events, which can cause death and disability, include:[6][13]

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.[50]

At least one patient with rheumatoid arthritis developed PML after treatment with rituximab.[51]

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.[52]

A major concern with continuous rituximab treatment is the difficulty to induce a proper vaccine response.[53] This was brought into focus during the COVID-19 pandemic, where persons with multiple sclerosis and rituximab treatment had higher risk of severe COVID-19.[54] In persons with rituximab treatment for multiple sclerosis, 9 of 10 patients with B cell counts of 40/µL or more developed protective levels of antibodies after vaccination with tozinameran.[55]

Mechanisms of action

Rituximab mechanisms of action; the three major independent mechanisms are (1) antibody dependent cellular cytotoxicity (ADCC), (2) complement mediated cytotoxicity (CMC), and (3) apoptosis; subset panel illustrates a schematic view of CD20 structure and rituximab.[56]
Rituximab binding to CD20. The CD20 proteins are sticking out of the cell membrane, and rituximab, the Y-shaped antibody, is binding to the CD20 proteins.

The 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. 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 is relatively ineffective in elimination of cells with low CD20 cell-surface levels.[57] 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.[58]

The following effects have been found:[59]

  • The Fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).[60]
  • Rituximab has a general regulatory effect on the cell cycle.
  • Preferential elimination of malignant B cells with high CD20 levels and high BCR signaling propensity, especially in chronic lymphocytic leukemia (CLL).[57]
  • It increases MHC II and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen).
  • It elicits shedding of CD23.
  • It downregulates the B cell receptor.
  • It induces apoptosis 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.[60]

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.[61]

History

Rituximab was developed by IDEC Pharmaceuticals under the name IDEC-C2B8. The U.S. patent for the drug was issued in 1998 and expired in 2015.[62]

Based on its safety and effectiveness in clinical trials,[63] 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.[64] 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.[65] In 2010, it was approved by the European Commission for maintenance treatment after initial treatment of follicular lymphoma.[66]

It is on the World Health Organization's List of Essential Medicines.[21]

In 2014, Genentech reclassified rituxan as a specialty drug, a class of drugs that are only available through specialty distributors in the US.[67] Because wholesalers discounts and rebates no longer apply, hospitals would pay more.[67]

Originally available for intravenous injection (e.g. over 2.5 hrs), in 2016, it gained EU approval in a formulation for subcutaneous injection for B-cell CLL/lymphoma (CLL).[68]

Society and culture

Economics

Patents on the drug expired in Europe in February 2013, and in the US in September 2016.[failed verification][69] (As of 2018), several biosimilars had been approved in the US, India, the European Union, Switzerland, Japan and Australia. The US FDA approved Truxima (rituximab-abbs) in 2018, Ruxience (rituximab-pvvr) in 2019 and Riabni (rituximab-arrx) in 2020. The latter is about $3600 per 500 mg, wholesale, list.[70][69][71][72]

Research

Chronic fatigue syndrome

Rituximab did not improve symptoms in patients with chronic fatigue syndrome in a trial published in 2019.[73][74] 22% of participants had serious events.[73] This potential use was investigated after improvements in chronic fatigue syndrome was seen in two cancer patients treated with rituximab.[75]

Intrathecal

For CNS diseases, rituximab could be administered intrathecally and this possibility is under study.[76]

Other anti-CD20 monoclonals

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

  • ocrelizumab, humanized (90%-95% human) B cell-depleting agent.
  • ofatumumab (HuMax-CD20) a fully human B cell-depleting agent.[77]
  • Third-generation anti-CD20s such as obinutuzumab have a glycoengineered Fc fragment (Fc)[78] with enhanced binding to Fc gamma receptors, which increase ADCC (antibody-dependent cellular cytotoxicity).[79] 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.[80]

References

  1. ↑ 1.0 1.1 "Rituximab Use During Pregnancy". 16 December 2019. https://www.drugs.com/pregnancy/rituximab.html. 
  2. ↑ Rituximab (rch) (CAS registry number: 174722-31-7)
  3. ↑ Australian Product Information. MabThera SC (rituximab)
  4. ↑ "MabThera 100 mg Concentrate for Solution for Infusion - Summary of Product Characteristics (SmPC)". 13 March 2021. https://www.medicines.org.uk/emc/product/3801/smpc. 
  5. ↑ "MabThera 1400 mg Solution for Subcutaneous Injection - Summary of Product Characteristics (SmPC)". 13 March 2021. https://www.medicines.org.uk/emc/product/5333/smpc. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 "Rituxan- rituximab injection, solution". 6 November 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b172773b-3905-4a1c-ad95-bab4b6126563. 
  7. ↑ 7.0 7.1 7.2 "Truxima- rituximab-abbs injection solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9af3ddc7-4217-417a-ac89-8704edc5bc44. 
  8. ↑ 8.0 8.1 8.2 "Ruxience- rituximab-pvvr injection solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f941fc61-f7a3-4e4a-ab7c-87c1667fa05b. 
  9. ↑ 9.0 9.1 9.2 "Riabni- rituximab-arrx injection solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da1c4de7-0e5b-4f72-97ec-7a8d368f085f. 
  10. ↑ "MabThera EPAR". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/mabthera. 
  11. ↑ "Rixathon EPAR". 15 June 2017. https://www.ema.europa.eu/en/medicines/human/EPAR/rixathon. 
  12. ↑ "Summary Basis of Decision (SBD) for Riximyo". 23 October 2014. https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00494&lang=en. 
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 "Rituximab". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/rituximab.html. 
  14. ↑ "Rituximab treatment of myasthenia gravis: A systematic review". Muscle & Nerve 56 (2): 185–196. August 2017. doi:10.1002/mus.25597. PMID 28164324. 
  15. ↑ "Update on maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis". Current Opinion in Rheumatology 29 (3): 248–253. May 2017. doi:10.1097/BOR.0000000000000382. PMID 28306595. 
  16. ↑ "EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts". Pathogens 7 (1): 28. March 2018. doi:10.3390/pathogens7010028. PMID 29518976. 
  17. ↑ "Rituximab Biosimilars Shown to Be Safe and Effective". https://www.medscape.com/viewarticle/883511. 
  18. ↑ "rituximab | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY". https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6780. 
  19. ↑ "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)". 29 February 2016. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-boxed-warning-and-new-recommendations-decrease-risk-hepatitis-b. 
  20. ↑ 20.0 20.1 Drugs Targeting B-Cells in Autoimmune Diseases. Springer Science & Business Media. 2013. pp. 1–4. ISBN 9783034807067. https://books.google.com/books?id=2l-4BAAAQBAJ&pg=PA4. 
  21. ↑ 21.0 21.1 World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  22. ↑ "FDA Approves Rituxan Plus Chemotherapy for the Most Common Type of Adult Leukemia" (Press release). Biogen.
  23. ↑ "Shifting Focus in the Therapeutics of Immunobullous Disease". Indian Journal of Dermatology 62 (3): 282–290. 2017. doi:10.4103/ijd.IJD_199_17. PMID 28584371. 
  24. ↑ "FDA approves rituximab plus chemotherapy for pediatric cancer indicati". 3 December 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rituximab-plus-chemotherapy-pediatric-cancer-indications.  This article incorporates text from this source, which is in the public domain.
  25. ↑ "Rituximab in Hodgkin lymphoma: is the target always a hit?". Cancer Treatment Reviews 37 (5): 385–390. August 2011. doi:10.1016/j.ctrv.2010.11.005. PMID 21183282. 
  26. ↑ "Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management". Hematology. American Society of Hematology. Education Program 2017 (1): 324–328. December 2017. doi:10.1182/asheducation-2017.1.324. PMID 29222274. 
  27. ↑ 27.0 27.1 "Rituxan Hycela- rituximab and hyaluronidase injection, solution". 3 December 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e5b7e82-f018-4eaf-ae78-d6145a906b20. 
  28. ↑ "Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis". The New England Journal of Medicine 350 (25): 2572–2581. June 2004. doi:10.1056/NEJMoa032534. PMID 15201414. 
  29. ↑ "Advances in rheumatology: new targeted therapeutics". Arthritis Research & Therapy 13 (Suppl 1): S5. May 2011. doi:10.1186/1478-6354-13-S1-S5. PMID 21624184. 
  30. ↑ "Safety of monoclonal antibodies for the treatment of multiple sclerosis". Expert Opinion on Drug Safety 16 (1): 89–100. January 2017. doi:10.1080/14740338.2017.1250881. PMID 27756172. 
  31. ↑ "Rituximab for relapsing-remitting multiple sclerosis". The Cochrane Database of Systematic Reviews (12): CD009130. December 2013. doi:10.1002/14651858.CD009130.pub3. PMID 24310855. 
  32. ↑ 32.0 32.1 "Popular Cancer Drug Linked to Often Fatal 'Brain Eating' Virus". Northwestern University News and Information. 20 May 2009. http://www.northwestern.edu/newscenter/stories/2009/05/bennett.html. 
  33. ↑ "FDA Warns of Safety Concern Regarding Rituxan in New Patient Population". U.S. Food and Drug Administration (FDA) (Press release). 18 December 2006. Archived from the original on 13 May 2009. Retrieved 29 April 2013.
  34. ↑ "Rituximab in autoimmune thrombotic thrombocytopenic purpura: A success story". European Journal of Internal Medicine 26 (9): 659–665. November 2015. doi:10.1016/j.ejim.2015.07.021. PMID 26293834. 
  35. ↑ "Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura". American Journal of Hematology 78 (4): 275–280. April 2005. doi:10.1002/ajh.20276. PMID 15795920. 
  36. ↑ "Long-term responses seen with rituximab in patients with ITP". Community Oncology 4 (2): 107. 2007. doi:10.1016/s1548-5315(11)70061-4. http://www.communityoncology.net/journal/articles/0402107.pdf. Retrieved 18 April 2007. 
  37. ↑ "Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome". Mayo Clinic Proceedings 78 (11): 1340–1346. November 2003. doi:10.4065/78.11.1340. PMID 14601692. 
  38. ↑ "Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin". The New England Journal of Medicine 355 (17): 1772–1779. October 2006. doi:10.1056/nejmoa062930. PMID 17065638. 
  39. ↑ "Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients". Archives of Neurology 65 (11): 1443–1448. November 2008. doi:10.1001/archneur.65.11.noc80069. PMID 18779415. 
  40. ↑ "Rituximab Treatment of Patients with Severe, Corticosteroid-Resistant Thyroid-Associated Ophthalmopathy". http://www.ophthalmologyjournaloftheaao.com/article/S0161-6420%2809%2900548-X/abstract. 
  41. ↑ "Immunomodulators and Rituximab in the Management of Autoimmune Pancreatitis". Pancreapedia. 11 June 2013. doi:10.3998/panc.2013.20. 
  42. ↑ "Immunologic and clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome". Pediatrics 115 (1): e115–e119. January 2005. doi:10.1542/peds.2004-0845. PMID 15601813. 
  43. ↑ "International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease". Arthritis & Rheumatology 67 (7): 1688–1699. July 2015. doi:10.1002/art.39132. PMID 25809420. 
  44. ↑ "Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab". JAMA Dermatology 151 (6): 646–650. June 2015. doi:10.1001/jamadermatol.2015.59. PMID 25901938. 
  45. ↑ "Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas". Cancers 14 (20): 5022. October 2022. doi:10.3390/cancers14205022. PMID 36291806. 
  46. ↑ "Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies". Arthritis and Rheumatism 64 (9): 3043–3051. September 2012. doi:10.1002/art.34468. PMID 22422012. 
  47. ↑ "Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies". Frontiers in Immunology 12: 731643. 30 August 2021. doi:10.3389/fimmu.2021.731643. PMID 34527001. 
  48. ↑ "Interstitial pneumonitis related to rituximab therapy". The New England Journal of Medicine 348 (26): 2690–1; discussion 2690–1. June 2003. doi:10.1056/NEJM200306263482619. PMID 12826649. 
  49. ↑ "Reports of Bowel Obstruction and Perforation with RITUXAN (rituximab)". Roche Canada. 10 November 2006. http://rochecanada.com/portal/servlet/staticfilesServlet?type=data&communityId=re753001&id=static/attachedfile/re7300002/re77300002/AttachedFile_04801.pdf. 
  50. ↑ "Rituximab (marketed as Rituxan) Information". 23 July 2015. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/rituximab-marketed-rituxan-information. 
  51. ↑ "Rituximab, RA and PML". https://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%209411700.pdf. 
  52. ↑ "Challenges in reporting meta-analyses of diagnostic accuracy studies". Annals of Internal Medicine 150 (6): 430. March 2009. doi:10.7326/0003-4819-150-6-200903170-00025. PMID 19293085. 
  53. ↑ "Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response". Annals of the Rheumatic Diseases 67 (7): 937–941. July 2008. doi:10.1136/ard.2007.077461. PMID 17981914. 
  54. ↑ "Increased rate of hospitalisation for COVID-19 among rituximab-treated multiple sclerosis patients: A study of the Swedish multiple sclerosis registry". Multiple Sclerosis 28 (7): 1051–1059. June 2022. doi:10.1177/13524585211026272. PMID 34212816. 
  55. ↑ "Factors Associated With Serological Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Rituximab". JAMA Network Open 5 (5): e2211497. May 2022. doi:10.1001/jamanetworkopen.2022.11497. PMID 35544139. 
  56. ↑ "A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections". Critical Reviews in Oncology/Hematology 97: 275–290. January 2016. doi:10.1016/j.critrevonc.2015.09.001. PMID 26443686. 
  57. ↑ 57.0 57.1 "Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels". Leukemia 32 (9): 2028–2031. September 2018. doi:10.1038/s41375-018-0211-0. PMID 30030508. 
  58. ↑ "Rituximab causes a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity". Blood 121 (23): 4694–4702. June 2013. doi:10.1182/blood-2013-02-482570. PMID 23613524. 
  59. ↑ "B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience". Annals of the Rheumatic Diseases 62 (Suppl 2): ii55–ii59. November 2003. doi:10.1136/ard.62.suppl_2.ii55. PMID 14532151. 
  60. ↑ 60.0 60.1 "Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion". Leukemia Research 111: 106684. December 2021. doi:10.1016/j.leukres.2021.106684. PMID 34438120. 
  61. ↑ "The epitope recognized by rituximab". Blood 108 (6): 1975–1978. September 2006. doi:10.1182/blood-2006-04-014639. PMID 16705086. 
  62. ↑ "Rituximab". Archived from the original. Error: If you specify |archiveurl=, you must also specify |archivedate=. https://web.archive.org/web/20140105002750/http://www.drugbank.ca/drugs/DB00073. 
  63. ↑ "IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma". Blood 90 (6): 2188–2195. September 1997. doi:10.1182/blood.V90.6.2188. PMID 9310469. 
  64. ↑ "Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma". Cancer Practice 6 (3): 195–197. 1998. doi:10.1046/j.1523-5394.1998.006003195.x. PMID 9652253. 
  65. ↑ Harrison's Principles of Internal Medicine, Longo et al. McGraw Hill Medical 2011 page 931
  66. ↑ "Roche Gets EC Nod for Follicular Lymphoma Maintenance Therapy". 29 October 2010. http://www.genengnews.com/gen-news-highlights/roche-gets-ec-nod-for-follicular-lymphoma-maintenance-therapy/81244149/. 
  67. ↑ 67.0 67.1 "Hospitals Furious at Cancer-Drug Price Hikes". Time. 27 October 2014. http://time.com/3541484/cancer-drug-price-hikes/. Retrieved 26 October 2015. 
  68. ↑ "EU approves second indication for subcutaneous form of Roche's rituximab". http://www.biopharma-reporter.com/Bio-Developments/EU-approves-indication-for-subcutaneous-form-of-Roche-s-MabThera/. 
  69. ↑ 69.0 69.1 "Biosimilars of Rituximab". Generics and Biosimilars Initiative. 14 April 2017. http://www.gabionline.net/Biosimilars/General/Biosimilars-of-rituximab. 
  70. ↑ "FDA approves first biosimilar for treatment of adult patients with non-Hodgkin's lymphoma". U.S. Food and Drug Administration (FDA) (Press release). 28 November 2018. Retrieved 11 November 2019.
  71. ↑ "Novartis abandons effort for U.S. approval of biosimilar rituximab". Reuters. 2 November 2018. https://www.reuters.com/article/us-novartis-rituximab/novartis-abandons-effort-for-u-s-approval-of-biosimilar-rituximab-idUSKCN1N72NA. 
  72. ↑ "Amgen Rituximab Biosimilar Gains FDA Approval". 17 December 2020. https://www.centerforbiosimilars.com/view/fda-approves-rituximab-biosimilar-from-amgen. 
  73. ↑ 73.0 73.1 "B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial". Annals of Internal Medicine 170 (9): 585–593. May 2019. doi:10.7326/M18-1451. PMID 30934066. 
  74. ↑ "Rituximab Fails to Improve Symptoms in ME/CFS". 2 April 2019. https://www.medscape.com/viewarticle/911197. 
  75. ↑ "Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome". British Journal of Pharmacology 174 (5): 345–369. March 2017. doi:10.1111/bph.13702. PMID 28052319. 
  76. ↑ "Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials". Current Drug Targets 15 (13): 1205–1214. 2014. doi:10.2174/1389450115666141029234644. PMID 25355180. 
  77. ↑ "Genmab.com / HuMax-CD20 (ofatumumab)". http://www.genmab.com/ScienceAndResearch/ProductsinDevelopment/HuMax-CD20.aspx. 
  78. ↑ "Fc-structure". http://www.healthvalue.net/Fc-structure.html. 
  79. ↑ "Monoclonal antibodies targeting cancer: 'magic bullets' or just the trigger?". Breast Cancer Research 3 (2): 86–90. 2001. doi:10.1186/bcr276. PMID 11250751. 
  80. ↑ "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review". Journal of Autoimmunity 57 (6): 1–13. February 2015. doi:10.1016/j.jaut.2014.12.002. PMID 25578468. 

External links



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