Infliximab
- CAS Number: 170277-31-3
Infliximab ( Remicade ® trade name, manufacturer Janssen Biotech Inc. ) is a chimeric monoclonal antibody. Infliximab is directed against the tumor necrosis factor α ( TNF ) and is therefore also known as TNF blockers.
TNF is in diseases of the rheumatoid type of central importance, it influences a variety of signaling systems of the immune system.
Areas of application
Treatment with infliximab is approved for the following diseases in the European Union:
- Rheumatoid arthritis
- Crohn's disease ( Infliximab is licensed for the treatment of Crohn's disease in children)
- Fistulas in Crohn's disease
- Ulcerative colitis
- Ankylosing spondylitis (Bechterew's disease )
- Psoriatic arthritis
- Psoriasis
Infliximab is used in severe cases and / or when conventional therapies (eg, NSAIDs, glucocorticoids, methotrexate ) were not sufficiently effective in patients. Infliximab is an immunosuppressive agent and is usually administered (except in ankylosing spondylitis ) together with methotrexate. It is usually administered per kg body weight dosed with 5 mg and dissolved in saline.
Development and marketing
1989 Junming Le and Jan Vilcek from the New York University School of Medicine generated the monoclonal antibody against TNF. 1998 has granted approval for Remicade in Crohn's disease the FDA. A year later, the approval was granted in Germany. 2001/2002 Infliximab has caused a stir in the art world after 202 deaths directly related to infliximab were known. Since then, increased security requirements, such as applicable Exclusion of tuberculosis before starting treatment. The treatment is very expensive. Janssen Biotech sells Remicade in America, Mitsubishi Tanabe in Japan, Xian Janssen in China, as well as MSD (formerly Schering -Plough, respectively. Essex Pharma) in Europe and in the rest of the world. In addition there are generic versions of other manufacturers. In September 2013, the first ( infliximab ) biosimilar ( generic ) for Europe was admitted.
History
Treatment with TNF blockers has significantly improved the possibilities of treatment of rheumatoid arthritis at the beginning of the 21st century. With progressive experience in the use of anti- TNF preparations rheumatologists, gastroenterologists, and dermatologists start more frequently the right to remission to meet. In rheumatoid arthritis the BeSt study showed the advantage of an early, aggressive combination therapy under close medical supervision. The 4-year data from this study showed that the entitlement to remission in some cases even on therapy-free remission, is now justified.
Structure
The variable antigen binding region occupies about 30% and the murine (mouse) portion, while the constant region having effector function accounts for about 70%, and of human origin. The constant region of the heavy chain is taken from an IgG1 antibody and the light chain is represented by a κ chain.
Pharmacology
The antibody is administered by intravenous infusion over two hours or longer. After first infusion the result infusions have it after 2 weeks and 6 weeks later following a rule - be repeated regularly after 8 weeks - depending on the effect.
Infliximab is distributed immediately in the vascular system ( Systemic Immediate Release = SIR), where it is still detectable up to 8 weeks later. He blocked the TNF - controlled the release of inflammatory mediators (cytokines ), leading in many cases after two weeks to a significant reduction of inflammation. Since the antibody is a chimeric product of human and animal protein ( human / mouse ), hypersensitivity reactions may occur. Also, infusion-related reactions such as fever, rash with itching, chills, shortness of breath and chest pain are possible. This seems less the murine origin of the variable portion to play a role, but rather the pattern of post-translational glycosylation and other production- related influences: The production process takes place in a murine myeloma cell line. In all manufacturing processes of biologics in cell cultures, the resulting modified proteins are different than in untreated human cells. As a consequence, are in cell cultures, such as in the Chinese hamster ovary often used in genetic engineering production processes ( CHO) cells, the proteins produced by other patterns come with sugar residues than in untreated human cells. However, the glycosylation pattern between two human individuals can vary greatly, which may for example lead to graft rejection in organ donation. In this respect have also full preparations from genetically engineered human proteins in a similar immunogenicity as chimeric proteins. A possible adverse infusion reaction can be effectively attenuated by prior administration of corticosteroids, antihistamines, and / or anti-inflammatory drugs or even prevented.
Since infliximab immune responses influenced and under treatment, among other latent tuberculosis can reappearance, the treatment must be preceded by a test for TB, which must be negative. Also, the blood needs to be monitored throughout the treatment period. For more information, especially about side effects, can be found at the links below.
Side effects
Infliximab has all TNF- alpha blockers the highest rate of anaphylactic reactions. This is due to the method of production, since it is not a human protein, but one of mice.