|Mass / length primary structure||144.2 kDa|
|ATC code||L04 AB02|
|Drug class||Immunosuppressant , monoclonal antibody|
TNFα is of central importance in diseases of the rheumatoid disease, it influences a large number of signal systems of the immune system.
Therapy with infliximab is approved in the European Union for the following diseases:
- Rheumatoid arthritis
- Crohn's disease (infliximab is also approved for the treatment of Crohn's disease in children)
- Fistula formation in Crohn's disease
- Ulcerative colitis
- Ankylosing spondylitis (Bechterew's disease)
- Psoriatic arthritis
Infliximab is used in severe cases and / or when conventional therapies (e.g. NSAIDs , glucocorticoids , methotrexate ) have not been sufficiently effective in patients. Infliximab is an immunosuppressant and in individual cases is also administered together with methotrexate. It is normally dosed at 5 mg per kg of body weight and administered intravenously as a solution in saline. Depending on the severity and course of the disease, the dosage can be increased up to 10 mg per body weight.
Development and marketing
In 1989 Junming Le and Jan Vilcek from New York University School of Medicine developed the monoclonal antibody against TNFα. In 1998, the FDA approved Remicade for the indication of Crohn's disease. Approval in the European Union followed a year later.
In 2001/2002 Remicade caused a sensation in the professional world after 202 deaths directly related to infliximab became known. Since then, increased precautionary measures, such as B. Exclusion of tuberculosis before starting treatment.
Treatment is very expensive. Janssen Biotech sells Remicade in America, Mitsubishi Tanabe in Japan, Xian Janssen in China and MSD (formerly from Schering-Plow and Essex Pharma) in Europe and the rest of the world. In September 2013, the first infliximab biosimilar ("biogeneric") was approved for Europe, in February 2015 it came onto the market in Germany: Remsima and Inflectra are bioidenticals, i.e. from the same manufacturing process by Celltrion and are sold in Germany by Mundipharma ( Remsima) and Pfizer (Inflectra).
Therapy with TNFα blockers has significantly improved the treatment options for rheumatoid arthritis at the beginning of the 21st century. With increasing experience in the use of anti-TNFα preparations, rheumatologists, gastroenterologists and dermatologists are increasingly beginning to meet the demand for remission . In rheumatoid arthritis, the BeSt study demonstrated the advantage of early, aggressive combination therapy under close medical supervision. The 4-year data from this study showed that the right to remission, in some cases even therapy-free remission, is now justified.
The variable, antigen-binding region makes up about 30% and is the murine (mouse) part, while the constant region with the effector function makes up about 70% and is 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.
The antibody is given as an intravenous infusion over two hours or more. After the first infusion, the subsequent infusions must then be repeated after 2 weeks and 6 weeks, later usually - depending on the effect - regularly after 8 weeks. In carefully selected patients who have tolerated at least 3 initial 2-hour Remicade infusions (induction phase) and who are receiving maintenance therapy, consideration may be given to administering subsequent infusions over a period of no less than 1 hour.
Infliximab is distributed immediately in the vascular system (Systemic Immediate Release = SIR), where it can still be detected up to 8 weeks later. There it blocks the TNFα-controlled release of inflammatory messenger substances ( cytokines ) and thus in many cases leads to a significant reduction in inflammation after two weeks. Since the antibody is a chimeric product made from human and animal protein (human / mouse), hypersensitivity reactions can occur. Infusion-related reactions such as fever , skin rash with itching , chills , shortness of breath and chest pain are also possible. The murine origin of the variable portion seems to play less of a role here than the pattern of post-translational glycosylation and other production-related influences: The manufacturing process takes place in a murine myeloma cell line. In all manufacturing processes for biological preparations in cell cultures, the proteins that are formed are modified differently than in untreated human cells. As a consequence, in cell cultures, such as in the Chinese hamster ovarian cells ( CHO cells ) that are often used in genetic engineering , the proteins formed are provided with sugar residues according to different patterns than in untreated human cells. However, the glycosylation patterns between two human individuals can also differ greatly, which can lead to transplant rejection in organ donation, for example. In this respect, preparations made from genetically engineered whole human proteins also show immunogenicity similar to that of chimeric proteins. A possible undesirable infusion reaction can be effectively weakened or even prevented by prior administration of glucocorticoids , antihistamines and / or anti-inflammatory drugs .
Since infliximab affects immune responses and, among other things, latent tuberculosis can flare up again during treatment, treatment must be preceded by a test for TB, which must be negative. The blood count must also be monitored during the entire treatment period. Further information, particularly on side effects, can be found at the links below.
Infliximab has the highest rate of anaphylactic reactions of any TNF-alpha blocker . This is due to the method of manufacture, since infliximab is not a human protein, but a chimeric antibody (ending -ximab), i. H. the variable part of the antibody is mouse protein.
Remicade ( MSD )
Flixabi from Samsung Bioepis has been approved in the EU since 2016.
- Singh JA, Christensen R, Wells GA, among others: Biologics for rheumatoid arthritis: an overview of Cochrane reviews . In: Cochrane Database Syst Rev . No. 4, 2009, p. CD007848. doi : 10.1002 / 14651858.CD007848.pub2 . PMID 19821440 .
- Remicade: Summary of the product characteristics, status: November 2009 (PDF; 360 kB) on the website of the European Medicines Agency EMEA .
- Remicade Co-Inventor And NYU Professor Of Microbiology Jan Vilcek, Pledge To NYU School Of Medicine , August 12, 2005.
- Infliximab: change in approval , Dtsch Arztebl 2002; 99 (6): A-320 / B-256 / C-244.
- Hospira's Inflectra (infliximab) the first biosimilar monoclonal antibody to be approved in Europe ( Memento from January 11, 2016 in the Internet Archive )
- Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, ao: Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial . (pdf) In: Arthritis Rheum . 52, No. 11, November 2005, pp. 3381-3390. doi : 10.1002 / art.21405 . PMID 16258899 .
- van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman YP, among others: Patient-reported outcomes in a randomized trial comparing four different treatment strategies in recent-onset rheumatoid arthritis . In: Arthritis Rheum. . 61, No. 1, January 2009, pp. 4-12. doi : 10.1002 / art.24367 . PMID 19116965 .
- Theo Dingermann, Angelika Vollmar: Immunology - Basics and Active Ingredients. WVG, Stuttgart 2005, ISBN 3-8047-2189-3 .
- Fleischmann R, Shealy D: Developing a new generation of TNFalpha antagonists for the treatment of rheumatoid arthritis . In: Mol. Interv. . 3, No. 6, September 2003, pp. 310-318. doi : 10.1124 / mi.3.6.310 . PMID 14993463 .
- Augustsson J, Eksborg S, Ernestam S, Gullström E, van Vollenhoven R: Low-dose glucocorticoid therapy decreases risk for treatment-limiting infusion reaction to infliximab in patients with rheumatoid arthritis . In: Ann Rheum Dis . 66, No. 11, November 2007, pp. 1462-1466. doi : 10.1136 / ard.2007.070771 . PMID 17502359 .
- Gardam MA, Keystone EC, Menzies R, among others: Anti-tumor necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management . In: Lancet Infect Dis . 3, No. 3, March 2003, pp. 148-155. PMID 12614731 .
- Keane J, Gershon S, Wise RP, inter alia: Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent . In: N. Engl. J. Med. . 345, No. 15, October 2001, pp. 1098-1104. PMID 11596589 .
- Mohan AK, Coté TR, Block JA, Manadan AM, Siegel JN, Braun MM: Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor . In: Clin. Infect. Dis. . 39, No. 3, August 2004, pp. 295-299. doi : 10.1086 / 421494 . PMID 15306993 .
- Pharmacology and Toxicology, Thieme Verlag
- Ankylosing spondylitis: Bechterew's disease, Wolfgang Miehle, RHEUMAMED.
- Se Young Lee: Samsung Bioepis receives final European approval for its Remicade copy. Reuters, May 30, 2016, accessed September 29, 2016 .