Adalimumab

drugbox-mab


source = Human
target = TNF
CAS_number = 331731-18-1
ATC_prefix = L04
ATC_suffix = AA17
PubChem =
DrugBank = BTD00049
C = 6428 | H = 9912 | N = 1694 | O = 1987 | S = 46
molecular_weight = 144190.3 g/mol
bioavailability = 64%
protein_bound =
metabolism =
elimination_half-life = 10-20 days.
pregnancy_US = B
pregnancy_AU = C
legal_UK = POM
legal_US = Rx-only
routes_of_administration = Subcutaneous

Adalimumab (brand name HUMIRA) is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab is a mouse-human chimeric antibody and etanercept is a TNF receptor-IgG fusion protein. TNFα inactivation has proven to be important in downregulating the inflammatory reactions associated with autoimmune diseases. As of 2008 adalimumab has been approved by the FDA for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, moderate to severe chronic psoriasis and juvenile idiopathic arthritis.

Humira (brand name is an abbreviation of "Human Monoclonal Antibody in Rheumatoid Arthritis") is marketed in both preloaded 0.8 ml syringes and also in preloaded pen devices, both injected subcutaneously, typically by the patient at home. It cannot be administered orally, because the digestive system would destroy the drug.

Humira's manufacturer is Abbott Laboratories.

Indications

Adalimumab, like its TNF inhibitor competitors, infliximab and etanercept, has proven versatile in proving effectiveness in treating several conditions.

Rheumatoid arthritis

Adalimumab has been shown to reduce the signs and symptoms of moderate-to-severe rheumatoid arthritis (RA) in adults. It has also been shown have efficacy in, and be approved for, moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 4 years of age and older. In RA it can be used alone or with methotrexate or similar medicines.

Psoriatic arthritis

Adalimumab has been shown to reduce the signs and symptoms of psoriatic arthritis (PsA) in adults, alone or with certain other medicines.

Ankylosing spondylitis

Adalimumab has been shown to reduce the signs and symptoms of, and is approved for treatment of, ankylosing spondylitis (AS) in adults.

Crohn’s disease

Adalimumab has been shown to reduce the signs and symptomsCite journal|last=Podolsky|first= Daniel K.|title=Inflammatory bowel disease|journal=New England Journal of Medicine|month=August|year=2002|volume=346|issue=6|pages=417–29
url=http://content.nejm.org/cgi/content/extract/347/6/417|accessdate=2006-07-02|pmid=12167685|doi=10.1056/NEJMra020831] of, and is approved for treatment of, moderate to severe Crohn’s disease (CD) in adults who have not responded well to conventional treatments and who have lost response to, or are unable to tolerate infliximab.

Plaque psoriasis

Adalimumab has been shown to treat moderate to severe chronic (lasting a long time) plaque psoriasis (Ps) in adults who have the condition in many areas of their body and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills).

Safety

Adalimumab is an immunosuppressant, and as such has a number of serious safety concerns, potentially fatal, typical of the TNF class. According to the product labeling, after a number of studies and reports of adverse events in patients receiving adalimumab, including serious and sometimes fatal blood disorders; serious infections including include TB (tuberculosis) and infections caused by viruses, fungi, or bacteria; rare reports of lymphoma and solid tissue cancers; rare reports of serious liver injury; and rare reports of demyelinating central nervous system disorders); rare reports of cardiac failure; the U.S. Food and Drug Administration issued a black box warning to doctors appearing in the product labeling of adalimumab and the other TNF drugs instructing them to screen and monitor potential patients more carefully [ FDA label - http://www.rxabbott.com/pdf/humira_medguide.pdf ] .

History

* April 1, 1995: Cambridge Antibody Technology Limited signs agreement with Knoll Aktiengesellschaft [ [http://www.cambridgeantibody.com/home/news_and_resources/news_archive/2003/cambridge_antibody_technology__humira] Cambridge Antibody Technology website]
* March 2, 2001: Abbott Laboratories acquires Knoll Pharmaceuticals from BASF
* June, 2001: Results from ARMADA, a double-blind, placebo-controlled clinical trial involving 271 patients with active rheumatoid arthritis despite treatment with methotrexate are announced. Among the results are that 50% of patients show a 50% improvement in ACR score.
* December 31, 2002: Humira approved by FDA

Lawsuit

In March 2003, British company Cambridge Antibody Technology (CAT), stated its wish to "initiate discussions regarding the applicability of the royalty offset provisions for Humira" Abbott Laboratories in the High Court of London. In November 2004, the trial began. In December 2004, the Judge, The Hon. Mr Justice Laddie, ruled for CAT stating "Abbott was in error when it made its first royalty payment to CAT calculated on the basis that only 2% of the Net Sales was due. It should have calculated on the basis of the full royalty of just over 5% and should have paid and continued to pay CAT accordingly." Abbott later paid CAT $23.7 million.

imilar agents

* Infliximab
* Etanercept

References

External links

* [http://www.humira.com HUMIRA Official site]
* [http://www.myhumira.com myHUMIRA Official site]
* [http://www.google.com/views?hl=en&safe=off&q=humira++view%3Atimeline&btnG=Search Google Timeline Search]