Omalizumab
| Omalizumab | ||
|---|---|---|
| Mass / length primary structure | 145.1 kDa | |
| Identifier | ||
| External IDs |
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| Drug information | ||
| ATC code | R03 DX05 | |
| DrugBank | BTD00081 | |
| Drug class | Monoclonal antibody | |
Omalizumab (trade name: Xolair ® , manufacturer: Novartis ) is a recombinant humanized monoclonal antibody against immunoglobulin E (anti-IgE) for the treatment of severe allergic bronchial asthma and for the treatment of chronic spontaneous urticaria . As anti-antibodies, it binds and neutralizes the IgE-type antibodies responsible for triggering the allergic reaction . The preparation takes place in a cell line from the ovary of Chinese hamster ( CHO cells ).
indication
In the USA it has been available for prescription for the treatment of moderate to severe persistent allergic bronchial asthma since July 2003, in Germany the active ingredient was only approved for the treatment of severe allergic asthma in October 2005. It should only be used if, despite therapy with a long-acting β 2 -sympathomimetic combined with high-dose inhaled glucocorticoids , patients have several severe asthma attacks per year. Approximately 50,000 patients are currently being treated with this drug in the USA, 3,500 in France and 1,500 in Germany. Since September 2009, omalizumab has also been approved in the EU for the treatment of children aged 6 and over.
Several studies have shown that omalizumab is also effective in treating urticaria , which the previous therapy has often not been able to treat with sufficient satisfaction. Since 2014, omalizumab has been approved in the EU as an add-on therapy for the treatment of chronic spontaneous urticaria in adults and adolescents (12 years and older) with an inadequate response to H1 antihistamines .
Mechanism of action
Omalizumab binds as an "anti- antibody " to free IgE and thus forms complexes that are ineffective in the cascade of allergy triggering. The binding of IgE to mast cells is reduced and the release of allergy-promoting mediators ( histamine and leukotrienes ) is reduced . During use, the concentration of free IgE drops by over 90%.
Side effects
Local reactions
Side effects are minimally increased pain compared to placebo, but more serious reactions at the injection site such as swelling, skin rashes, itching and also headaches are described.
Allergies, anaphylaxis
Particularly noteworthy are life-threatening anaphylactic reactions , some of which were observed more than 24 hours after the injection, both after the first and after subsequent applications (even after more than a year). Based on ADR reports, the overall incidence in the USA is estimated at 0.2%. These symptoms can set in within minutes, hours or days after the injection of omalizumab: 35% of the reactions occurred up to 30 minutes after the injection, in 14% between 6 and 12 hours, and in 5% of the cases in the range from 1 to 4 Days. In 39% the reaction appeared at the first dose, in 19% at the second and 10% at the third dose, the remaining 32% at later time points. Repeating the application of the active ingredient after anaphylaxis is particularly dangerous. In 18 of 23 re-exposed people, some more severe anaphylactic symptoms recur.
Possible symptoms of such anaphylaxis are bronchospasm , drop in blood pressure, syncope (sudden, short-lasting loss of consciousness), hives , angioedema , shortness of breath, generalized itching and the like. a. After a recommendation from the Food and Drug Administration ( Food and Drug Administration of the USA) should be monitored for a certain time after injection medical patients. A German panel of experts points out that no anaphylaxis after administration of omalizumab has so far occurred in patients with urticaria, but nevertheless recommends follow-up observation of the patient in the practice analogous to desensitization , i.e. at least 30 minutes. The causes of the anaphylactic and anaphylactoid (late) reactions are still unclear, specific long-term studies are still lacking.
Malignant tumors
A warning originally issued in a summary report by the FDA in November 2009 regarding increased tumor formation under therapy with omalizumab compared to placebo has since been withdrawn because a large study with over 7000 patients could not determine an increased risk of tumors.
Other side effects
Other side effects included sometimes pronounced changes in the blood count ( thrombopenia ) and hair loss. The infection rate with worms (helminths) is also increased, since IgE is involved in the defense against worm infections .
Other Information
A 150 mg vial costs around € 530 in Germany.
literature
- RC Strunk, GR Bloomberg: Omalizumab for asthma. N Engl J Med. (2006) 354 (25): pp. 2689-2695, PMID 16790701
- RY Lin et al .: Omalizumab-associated anaphylactic reactions reported between January 2007 and June 2008 . Ann Allergy Asthma Immunol . (2009) 103 (5): pp. 442-445, PMID 19927545
Web links
- Publication for the registration study
- European Public Assessment Report (EPAR) for Xolair ® ( Memento of September 18, 2006 in the Internet Archive )
Individual evidence
- ↑ Novartis press release
- ↑ Maurer M et al .: Omalizumab for the Treatment of Chronic Idiopathic or Spontaneous Urticaria . doi : 10.1056 / NEJMoa1215372
- ↑ Avoxa ?? Mediengruppe Deutscher Apotheker GmbH: Pharmaceutical newspaper online: Urticaria: one, four, grandma. Retrieved June 15, 2017 .
- ↑ Specialist information on Xolair at open drug database .
- ↑ Information for Healthcare Professionals: Omalizumab (FDA) .
- ↑ FDA warning notice anaphylaxis (PDF; 36 kB)
- ^ Christian Termeer, Petra Staubach, Hjalmar Kurzen, Klaus Strömer, Rolf Ostendorf: Chronic spontaneous urticaria - a management pathway for patients with chronic spontaneous urticaria . In: JDDG: Journal of the German Dermatological Society . tape 13 , no. 5 , May 1, 2015, p. 419-428 , doi : 10.1111 / ddg.12633 .
- ↑ Slides for the November 18, 2009 Meeting of the Pulmonary-Allergy Drugs Advisory Committee - Slide No. 8 f (PDF; 1.5 MB).
- ↑ Aidan Long, Abdelkader Rahmaoui, Kenneth J. Rothman, Eva Guinan, Mark Eisner: Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab . In: Journal of Allergy and Clinical Immunology . tape 134 , no. 3 , September 1, 2014, p. 560-567.e4 , doi : 10.1016 / j.jaci.2014.02.007 .
