Table of Contents
3. Clinical Uses
4. Warnings and Limitations
M. D. Schafranski
Medicina Interna e Reumatologia, Fragilidades de um modelo ainda imperfeito, Brazil
A. B. Merlini
A. L. O. Prestes
Series: Pharmacology – Research, Safety Testing and Regulation, Immunology and Immune System Disorders
Infliximab, a chimeric immunoglobulin G1 monoclonal antibody which contains a human constant region and a mouse-derived murine variable region, binds specifically to the soluble and transmembrane tumor necrosis factor-alpha (TNF-), avoiding the coupling of this cytokine and its receptors and, consequently, neutralizing its biology activity, such as the induction of pro-inflammatory cytokines (such as interleukin-1 and interleukin-6), leucocytes migration, endothelial permeability, adhesion molecules expression, neutrophils and eosinophils activation, prostaglandin synthesis and fibroblast proliferation. The antibody exerts its effects by fixing complement, inducting complement-depended and cell-mediated lyses. For these actions, it uses T- and B-cells, neutrophil and endothelial cells.
It is administered intravenously and it allocates mainly in the intravascular compartment. Doses of 1, 5, 10 or 20 mg/kg associate linearly with major concentrations. When 5 mg/kg is infused, it results in a major concentration of 118 µg/ml. Its mean half-life is approximately 9,5 days. Therapeutic managements interlards in accordance to the underlying condition.
TNF- inhibitors cause a inflammatory suppression in the joint spaces, and also, in a global way, act in the immune system favorably controlling the symptoms associated with chronic inflammation. Most of infliximab indications for autoimmune inflammatory diseases, such as psoriatic arthritis, rheumatoid arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, and others are strongly supported by evidence-based data. Beyond the use in psoriasis, some dermatological conditions are being included in the spectrum of anti TNF- therapy targets. One of these conditions is the Sneddon-Wilkinson disease, characterized by the development of subcorneal pustules, in which this therapy was described as satisfactory by some authors. Otherwise, the role of anti-TNF- therapy in conditions as sarcoidosis and in some demyelinating diseases, like Hermansky-Pudlak syndrome, has not been definitely established. Finally, guidelines involving its usage in refractory Behçet disease are still being developed.
As side effects, infliximab has been implicated in the development of malignancies, hepatitis B virus and tuberculosis reactivation, hepatotoxicity and worsening of heart failure. It can also cause a lupus-like syndrome, exacerbation or new onset occurs of demyelinating disease and the formation of autoantibodies. Recently, Food and Drug Administration (FDA) issued a warning on its use, taking into account some reports of lymphoma related to previous use of the drug. Its pregnancy indications as well as the predisposition of lung cancer when used in Crohn’s disease are still uncertain. Also, patients taking corticosteroids with TNF- blocking agents can predispose to serious and fatal infections due to bacterial, invasive fungal, viral or other opportunistic pathogens, as long as TNF- is required for intracellular killing of pathogens, since it is released from neutrophils and macrophages upon first encounter with them.
Although infliximab has already proved to be an effective and promising alternative to a plethora of autoimmune and inflammatory conditions, it also presents a wide array of side effects and cautions regarding its usage. So, it is mandatory to the health-care provider to monitor infliximab patients for possible side effects and complications. (Imprint: Nova Biomedical )