Movatterモバイル変換


[0]ホーム

URL:


Jump to content
WikipediaThe Free Encyclopedia
Search

Alemtuzumab

From Wikipedia, the free encyclopedia
(Redirected fromLemtrada)
Medication

Pharmaceutical compound
Alemtuzumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (fromrat)
TargetCD52
Clinical data
Trade namesCampath, Mabcampath, Lemtrada, others
AHFS/Drugs.comMonograph
MedlinePlusa608053
License data
Pregnancy
category
Routes of
administration
Intravenous infusion
ATC code
Legal status
Legal status
Pharmacokinetic data
Eliminationhalf-life~288 hrs
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6468H10066N1732O2005S40
Molar mass145454.20 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Alemtuzumab, sold under the brand namesCampath andLemtrada among others, is amedication used to treatchronic lymphocytic leukemia andmultiple sclerosis.[8] In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment.[8] It is given byinjection into a vein.[8]

It is amonoclonal antibody that binds toCD52, a protein present on the surface of maturelymphocytes, but not on thestem cells from which these lymphocytes are derived. After treatment with alemtuzumab, these CD52-bearing lymphocytes are targeted for destruction.

Alemtuzumab was approved for medical use in the United States in 2001.[8] (Mab)Campath was withdrawn from the markets in the US and the EU in 2012, to prepare for a higher-priced relaunch of Lemtrada aimed at multiple sclerosis.[9]

Medical uses

[edit]

Chronic lymphocytic leukemia

[edit]

Alemtuzumab is used for the treatment of B-cell chronic lymphocytic leukemia in people who have been treated with alkylating agents and who have failedfludarabine therapy. It is an unconjugated antibody, thought to work via the activation ofantibody-dependent cell-mediated cytotoxicity.[10][unreliable medical source?]

Multiple sclerosis

[edit]

It is used for the relapsing remitting form of multiple sclerosis.[8] A 2017 Cochrane meta-analysis of studies comparing alemtuzumab to interferon beta 1a concluded that annual cycles of alemtuzumab probably reduces the proportion of people that experience relapse and may reduce the proportion of people who experience disability worsening and new T2 lesions on MRI, with adverse events found to be similarly high for both treatments.[11] However the low-to-moderate levels of evidence in the included, existing studies were noted and the need for larger high-quality randomised, double-blind, controlled trials comparing mono or combination therapy with alemtuzumab was highlighted.[11]

Contraindications

[edit]

Alemtuzumab is contraindicated in patients who have active infections, underlying immunodeficiency (e.g., seropositive for HIV), or known type I hypersensitivity or anaphylactic reactions to the substance.[6]

Adverse effects

[edit]

In November 2018, the USFood and Drug Administration (FDA) issued a safety announcement[12] warning about rare but serious instances of stroke and blood vessel wall tears in multiple sclerosis patients who have received Lemtrada (alemtuzumab), mostly occurring within one day of initiating treatment and leading in some cases to permanent disability and even death.

In addition to the 13 cases to which the FDA safety announcement refers, a further five cases of spontaneous intracranial hemorrhage have been retrospectively identified from four US multiple sclerosis centers in correspondence published online in February 2019.[13]

In April 2019, thePharmacovigilance Risk Assessment Committee (PRAC) of theEuropean Medicines Agency (EMA) reported that it has started a review of the multiple sclerosis medicine Lemtrada (alemtuzumab) following new reports of immune-mediated conditions and of problems with the heart and blood vessels with this medicine, including fatal cases. The PRAC advised that while the review is ongoing, Lemtrada should only be started in adults with relapsing-remitting multiple sclerosis that is highly active despite treatment with at least two disease-modifying therapies (a type of multiple sclerosis medicine) or where other disease-modifying therapies cannot be used. The PRAC further advised that patients being treated with Lemtrada who are benefitting from it may continue treatment in consultation with their doctor.[14]

Very common adverse reactions associated with alemtuzumab infusion in people with multiple sclerosis include upper respiratory tract and urinary tract infections, herpes virus infections, lymphopenia, leucopenia, changes in thyroid function, tachycardia, skin rashes, pruritus, pyrexia, and fatigue.[15] The Summary of Product Characteristics provided in the electronic Medicines Compendium [eMC[16]] further lists common and uncommon adverse reactions that have been reported for Lemtrada, which include serious opportunistic nocardial infections and cytomegalovirus syndrome.[17][18][19]

Alemtuzumab can also precipitateautoimmune disease through the suppression ofregulatory T cell populations and/or the emergence of autoreactive B-cells.[20][21]

Cases of multiple sclerosis reactivation/relapse have also been reported[22]

Biochemical properties

[edit]

Alemtuzumab is a recombinant DNA-derived humanizedIgG1 kappa monoclonal antibody that is directed against the cell surface glycoproteinCD52.[23]

History

[edit]

The origins of alemtuzumab date back to Campath-1 which was derived from the rat antibodies raised against human lymphocyte proteins byHerman Waldmann and colleagues in 1983.[24] The name Campath derives from thepathology department ofCambridge University.

Initially, Campath-1 was not ideal for therapy because patients could, in theory, react against the foreign rat protein determinants of the antibody. To circumvent this problem,Greg Winter and his colleagues humanised Campath-1, by extracting thehypervariable loops that had specificity for CD52 and grafting them onto a human antibody framework. This became known as Campath-1H and serves as the basis for alemtuzumab.[25]

While alemtuzumab started life as a laboratory tool for understanding the immune system, within a short time it was clinically investigated for use to improve the success of bone marrow transplants and as a treatment for leukaemia, lymphoma, vasculitis, organ transplants, rheumatoid arthritis and multiple sclerosis.[26]

Society and culture

[edit]

Economics

[edit]

Campath as a medication was first approved for B-cell chronic lymphocytic leukemia in 2001. It is marketed byGenzyme, which acquired the worldwide rights fromBayer AG in 2009. Genzyme was bought bySanofi in 2011. In August/September 2012 Campath was withdrawn from the markets in the US and EU. This was done to preventoff-label use of the drug to treat multiple sclerosis and to prepare for a relaunch under the brand name Lemtrada, with a different dosage aimed at multiple sclerosis treatment, this is expected to be much higher-priced.[9]

In February 2011, Sanofi-Aventis, since renamedSanofi, acquired Genzyme, the manufacturer of alemtuzumab.[27] The acquisition was delayed by a dispute between the two companies regarding the value of alemtuzumab.

In August 2012, Genzyme surrendered the license for all presentations of alemtuzumab,[28] pending regulatory approval to reintroduce it as a treatment formultiple sclerosis. Concerns[29] that Genzyme would later bring to market the same product at a much higher price proved correct.

Names

[edit]

Alemtuzumab is theinternational nonproprietary name.[30]

Research

[edit]

Antiviral properties

[edit]

In an in-vitro experiment, it has been shown that alemtuzumab has antiviral properties againstHIV-1.[31]

Graft-versus-host disease

[edit]

A 2009 retrospective study of alemtuzumab (10 mg IV weekly) in 20 patients (no controls) with severe steroid-resistant acute intestinalgraft-versus-host disease after allogeneichematopoietic stem cell transplantation (HSCT) demonstrated improvement. Overall response rate was 70%, with complete response in 35%.[32] In this study, the median survival was 280 days. Important complications following this treatment includedcytomegalovirus reactivation, bacterial infection, and invasiveaspergillosis infection.[32]

References

[edit]
  1. ^"Alemtuzumab Use During Pregnancy".Drugs.com. 22 August 2022. Retrieved6 January 2024.
  2. ^"TGA eBS - Product and Consumer Medicine Information Licence".
  3. ^"TGA eBS - Product and Consumer Medicine Information Licence".
  4. ^"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)".nctr-crs.fda.gov.FDA. Retrieved22 October 2023.
  5. ^"Campath- alemtuzumab injection".DailyMed. 3 May 2023. Retrieved6 January 2024.
  6. ^ab"Lemtrada- alemtuzumab injection, solution, concentrate".DailyMed. 23 May 2023. Retrieved6 January 2024.
  7. ^"Lemtrada EPAR".European Medicines Agency. 12 September 2013. Retrieved6 January 2024.
  8. ^abcde"Alemtuzumab Monograph for Professionals".Drugs.com. American Society of Health-System Pharmacists. Retrieved15 July 2019.
  9. ^abMcKee S (21 August 2012)."Sanofi withdraws Campath in US and EU".Pharma Times Online. Pharma Times. Archived fromthe original on 4 March 2016. Retrieved6 November 2012.
  10. ^"About Campath". Genzyme. Archived fromthe original on 14 July 2011.
  11. ^abZhang J, Shi S, Zhang Y, Luo J, Xiao Y, Meng L, et al. (November 2017)."Alemtuzumab versus interferon beta 1a for relapsing-remitting multiple sclerosis".The Cochrane Database of Systematic Reviews.11 (11): CD010968.doi:10.1002/14651858.CD010968.pub2.PMC 6486233.PMID 29178444.
  12. ^"FDA warns about rare but serious risks of stroke and blood vessel wall tears with multiple sclerosis drug Lemtrada (alemtuzumab)".FDA Drug Safety Communication. U.S.Food and Drug Administration (FDA). 29 November 2018.
  13. ^Azevedo CJ, Kutz C, Dix A, Boster A, Sanossian N, Kaplan J (April 2019). "Intracerebral haemorrhage during alemtuzumab administration".The Lancet. Neurology.18 (4):329–331.doi:10.1016/S1474-4422(19)30076-6.PMID 30777657.S2CID 72334305.
  14. ^"Use of multiple sclerosis medicine Lemtrada restricted while PRAC review is ongoing".Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC). European Medicines Agency. 12 April 2019.
  15. ^"LEMTRADA 12 mg concentrate for solution for infusion - Summary of Product Characteristics (SMPC) - (Emc)". Archived fromthe original on 6 May 2021. Retrieved7 April 2019.
  16. ^"Home - electronic medicines compendium (emc)".www.medicines.org.uk. Retrieved16 February 2024.
  17. ^Sheikh-Taha M, Corman LC (May 2017). "Pulmonary Nocardia beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis".Multiple Sclerosis.23 (6):872–874.doi:10.1177/1352458517694431.PMID 28290754.S2CID 206702778.
  18. ^Clerico M, De Mercanti S, Artusi CA, Durelli L, Naismith RT (May 2017). "Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab".Multiple Sclerosis.23 (6):874–876.doi:10.1177/1352458516688350.PMID 28290755.S2CID 206702649.
  19. ^Brownlee WJ, Chataway J (May 2017)."Opportunistic infections after alemtuzumab: New cases of norcardial infection and cytomegalovirus syndrome".Multiple Sclerosis.23 (6):876–877.doi:10.1177/1352458517693440.PMID 28290753.S2CID 30519152.
  20. ^Costelloe L, Jones J, Coles A (March 2012). "Secondary autoimmune diseases following alemtuzumab therapy for multiple sclerosis".Expert Review of Neurotherapeutics.12 (3):335–341.doi:10.1586/ern.12.5.PMID 22364332.S2CID 34738692.
  21. ^Aranha AA, Amer S, Reda ES, Broadley SA, Davoren PM (2013). "Autoimmune thyroid disease in the use of alemtuzumab for multiple sclerosis: a review".Endocrine Practice.19 (5):821–828.doi:10.4158/EP13020.RA.PMID 23757618.
  22. ^Wehrum T, Beume LA, Stich O, Mader I, Mäurer M, Czaplinski A, et al. (February 2018). "Activation of disease during therapy with alemtuzumab in 3 patients with multiple sclerosis".Neurology.90 (7):e601 –e605.doi:10.1212/WNL.0000000000004950.PMID 29352101.S2CID 3319939.
  23. ^Klement A (7 January 2014). "Multiple-Sklerose-Behandlung".Österreichische Apothekerzeitung (in German) (1/2014): 24f.
  24. ^Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, et al. (October 1983)."Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement".Blood.62 (4):873–882.doi:10.1182/blood.V62.4.873.873.PMID 6349718.
  25. ^Riechmann L, Clark M, Waldmann H, Winter G (March 1988)."Reshaping human antibodies for therapy".Nature.332 (6162):323–327.Bibcode:1988Natur.332..323R.doi:10.1038/332323a0.PMID 3127726.S2CID 4335569.
  26. ^"The life story of a biotechnology drug: Alemtuzumab". What is Biotechnology?.
  27. ^Whalen J, Spencer M (17 February 2011)."Sanofi Buys Genzyme for over $20 billion".The Wall Street Journal.
  28. ^Hussein J (9 August 2012)."Discontinuation of licensed supplies of alemtuzumab (Mabcampath)"(PDF). United Kingdom: National Institute for Health and Care Excellence.
  29. ^"Multiple sclerosis: New drug 'most effective'".BBC News. 1 November 2012. Retrieved1 November 2012.
  30. ^World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90".WHO Drug Information.37 (3).hdl:10665/373341.
  31. ^Ruxrungtham K, Sirivichayakul S, Buranapraditkun S, Krause W (January 2016)."Alemtuzumab-induced elimination of HIV-1-infected immune cells".Journal of Virus Eradication.2 (1):12–18.doi:10.1016/S2055-6640(20)30694-4.PMC 4946689.PMID 27482429.
  32. ^abSchnitzler M, Hasskarl J, Egger M, Bertz H, Finke J (August 2009)."Successful treatment of severe acute intestinal graft-versus-host resistant to systemic and topical steroids with alemtuzumab".Biology of Blood and Marrow Transplantation.15 (8):910–918.doi:10.1016/j.bbmt.2009.04.002.PMID 19589480.

External links

[edit]
Demyelinating diseases of thecentral nervous system
Signs and symptoms
Investigations and diagnosis
Approved treatment
Other treatments
Demyelinating diseases
Autoimmune
Inflammatory
Hereditary
Other
Other
CImonoclonal antibodies ("-mab")
Receptor tyrosine kinase
Others for solid tumors
Leukemia/lymphoma
Other
Tyrosine kinase inhibitors ("-nib")
Receptor tyrosine kinase
Non-receptor
Other
Intracellular
(initiation)
Antimetabolites
Macrolides/
otherIL-2 inhibitors
IMiDs
Intracellular
(reception)
IL-1 receptor antagonists
mTOR
Extracellular
Antibodies
Monoclonal
Serum target
(noncellular)
Cellular
target
Unsorted
Polyclonal
-cept (Fusion)
Unsorted
Tumor
Human
Mouse
Chimeric
Humanized
Rat/mouse hybrid
Chimeric + humanized
Portal:
Authority control databases: NationalEdit this at Wikidata
Retrieved from "https://en.wikipedia.org/w/index.php?title=Alemtuzumab&oldid=1241948726"
Categories:
Hidden categories:

[8]ページ先頭

©2009-2025 Movatter.jp