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3.2.8 Tumor Necrosis Factor
ОглавлениеTwo of the top five best‐selling drugs of all time are tumor necrosis factor (TNF) inhibitors, which is an impressive marketing feat despite their relatively specific use for various rare autoimmune diseases.6 TNF is a major proinflammatory cytokine affecting various aspects of the immune system with a wide range of biologic effects including anti‐tumor and antiviral activity. In the body, TNF is a transmembrane protein (tmTNF) that gets cleaved to soluble TNF (solTNF); both forms are biologically active, but with distinct roles that translate to the safety and efficacy profile of TNF inhibitors. For example, inhibiting solTNF results in anti‐inflammatory effects, whereas inhibiting tmTNF results in increased susceptibility to infection.21
The TNF molecule itself has limited therapeutic activity due to extreme toxicity. The more commonly clinically used agents are the TNF antagonists. Remicade® (infliximab) and Humira® (adalimumab) are both IgG mAbs and work by competitively inhibiting the binding of TNF to its receptors. While their mechanism of action is similar, the pharmacokinetic and pharmacodynamic properties of the various drugs in the TNF inhibitor class are different. These unique properties can lead to variations in safety and clinical efficacy for the treatment of autoimmune conditions. It has been noted that up to one‐third of RA patients do not respond to anti‐TNF therapy due to genetic factors.21
Table 3.5 Examples of cytokine drugs and diseases treated.
Source: Food and Drug Administration (FDA) DailyMed.17
| Type of cytokine | Drug name | Manufacturer | Disease(s) treated (per FDA labeling) |
|---|---|---|---|
| Interferon | Actimmune® (interferon gamma‐1b) | Horizon Pharma Inc. | Chronic granulomatous disease; Severe, malignant osteopetrosis |
| Avonex® (interferon beta‐1a) | Biogen Inc. | Multiple sclerosis | |
| Betaseron® (interferon beta‐1b) | Bayer HealthCare | Multiple sclerosis | |
| Extavia® (interferon beta‐1b) | Novartis | Multiple sclerosis | |
| Intron A® (interferon alfa‐2b) | Merck Sharp & Dohme Corp | Hairy cell leukemia; Malignant melanoma; Follicular lymphoma; Condylomata acuminate; AIDS‐related Kaposi's sarcoma; Chronic hepatitis C; Chronic hepatitis B | |
| Interleukin | Actemra® (tocilizumab) | Genentech | Rheumatoid arthritis; Giant cell arteritis; Polyarticular juvenile idiopathic arthritis; Systemic juvenile idiopathic arthritis; Cytokine release syndrome |
| Cosentyx® (secukinumab) | Novartis | Plaque psoriasis; Psoriatic arthritis; Ankylosing spondylitis | |
| Dupixent® (dupilumab) | Sanofi‐Aventis | Atopic dermatitis; Asthma | |
| Kineret® (anakinra) | Swedish Orphan Biovitrum AB | Rheumatoid arthritis; Cryopyrin‐associated periodic syndromes | |
| Nucala® (mepolizumab) | GlaxoSmithKline | Severe asthma | |
| Zinbryta® (daclizumab) | Abbvie | Multiple sclerosis | |
| Tumor necrosis factor | Enbrel® (etanercept) | Amgen | Rheumatoid arthritis; Polyarticular juvenile idiopathic arthritis; Psoriatic arthritis; Ankylosing spondylitis; Plaque psoriasis |
| Humira® (adalimumab) | Abbvie | Rheumatoid arthritis; Juvenile idiopathic arthritis; Psoriatic arthritis; Ankylosing spondylitis; Plaque psoriasis; Crohn's disease; Pediatric Crohn's disease; Ulcerative colitis; Hidradenitis suppurativa; Uveitis | |
| Remicade® (infliximab) | Janssen Biotech | Crohn's disease; Pediatric Crohn's disease; Ulcerative colitis; Pediatric ulcerative colitis; Rheumatoid arthritis; Ankylosing spondylitis; Psoriatic arthritis; Plaque psoriasis | |
| Erythropoietin | Aranesp® (darbepoetin alfa) | Amgen | Anemia due to chronic kidney disease; Anemia due to chemotherapy in patients with cancer |
| Procrit® (erythropoietin) | Janssen | Anemia due to chronic kidney disease; Anemia due to zidovudine in patients with HIV‐infection; Anemia due to chemotherapy in patients with cancer; Reduction of allogenic red blood cell transfusions in patients undergoing elective, noncardiac surgery; Nonvascular surgery | |
| Colony stimulating growth factor | Neulasta® (pegfilgrastim) | Amgen | Patients with cancer receiving myelosuppressive chemotherapy; Patients with hematopoietic subsyndrome of acute radiation syndrome |
| Vascular endothelial growth factor | Avastin® (bevacizumab) | Genentech | Metastatic colorectal cancer |
