• Trade name: Micera 
• Type: ESA
• Function: stimulates erythropoiesis, longer half life (134 hours) (PEGylated- PEG enhances the stability of the protein). Continuous erythropoietin receptor activator. 
•  Major Use:Anemia, chronic kidney disease or chronic renal failure, adjunct to chemotherapy, preoperative preparation. Usually given for anemia in chronic kidney disease though. 
• Not approved in the US 

• Trade name: Affymax
• Type: ESA
• Function: Same, non-rhEPO PEGylated synthetic dimeric peptide
•  Major Use: In phase III clinical trials to treat anemia in patients with chronic renal failure. 
• Hematide™ (Affymax) is a synthetic dimeric peptide-based ESA which is being evaluated for the treatment of anemia in patients with chronic renal failure. It may enter market in 2011

• Trade name: Neupogen
• Type: G-CSF (recombinant - human derived)
• Function: stimulates neutrophil proliferation, differentiation, and migration. 
•  Major Use: Neutropenia in AIDS or post-chemotherapy or bone-marrow transplantation; severe neutropenia

• Trade name:Neulasta
• Type: G-CSF [A covalently linked analog of recombinant G-CSF (filgrastim) and monomethoxypolyethylene glycol (PEG)]
• Function:Stimulates neutrophil proliferation, differentiation, and migration, but has a longer half life than neupogen 
•  Major Use: Neutropenia in AIDS or post-chemotherapy or bone-marrow transplantation; severe neutropenia

• Trade name:Leukine 
• Type: GM-CSF (recombinant) 
• Function:Stimulates proliferation and differentiation of neutrophils, eosinophils, and monocytes

•  Major Use: Following induction chemotherapy in older adults with acute myelogenous leukemia (AML). Before and/or after peripheral blood stem cell transplantation. Mobilizes progenitor cells and helps with myeloid reconstitution after transplant. Protects against infections because it accelerates myeloid recovery, including increases in the number and activity of neutrophils (bacteria protection), monocytes/macrophages (fungi/virus protection) and myeloid-derived dendritic cells (virus protection).  These three key cells provide protection from multiple pathogens
• This drug shortens the time it takes neutrophils to recover while significantly reducing the number of deaths that would result from infections. 

Trade Name: Kineret

Type: recombinant IL-1 protein

Mechanism of Action: IL-1 receptor antagonist

Indications: Rheumatoid arthritis 

Approval: 2001

Trade Name: Humira

Type: Human Mab

Mechanism of Action: TNF-alpha blocker

Indications: Rheumatoid Arthritis; Plaque Psoriasis; Crohn’s Disease; Psoriatic Arthritis; Ankylosing Spondlyitis; Juvenile Idopathic Arthritis.

Approval: 2002

Other Info: 

• 1st fully Human Mab
• Taken by injection
• Half life about 10 -20 days
• Pre-filled and pre-measured syringe containing 40 mg (0.8 mL) or… Humira pen
• No mixing, no measuring, no filling
• Usually injected once every two weeks

Trade Name: Raptiva

Type: ---

Mechanism of Action: ----

Indications: WITHDRAWN FROM MARKET

Approval: 2003

Trade Name: Enbrel

Type: Infusion Protein

Mechanism of Action: TNF-alpha blocker

Indications: Rheumatoid Arthritis; Plaque Psoriasis; Psoriatic Arthritis; Ankylosing Spondlyitis; Juvenile IdopathicArthritis

Approval: 2003

Other Info: 

• Half life is 3- 5 days
• This fusion protein is made up of the Fc portion of IgG, and a TNF-a receptor portion (mimics the action of TNF-a receptors on cell surface) , and blocks action of soluble TNF-a.
• Administered using 25-50mg in a sureclick prefilled autoinjector. 

Trade Name: Amevive

Type: Fusion Protein 

Mechanism of Action: Blocks CD-2 on memory T cells

Indications: plaque psoriasis 

Approval: 2003

Other Info: 

Trade Name: Orencia 

Type: Fusion Protein

Mechanism of Action: Blocks CD 80/86 on APC

Indications: Juvenile Idiopathic Arthritis and Rheumatoid Arthritis

Approval: 2005

Other Info: 

Trade Name: Cimzia 

Type: Humanized Mab + PEG - NO-Fc

Mechanism of Action: TNF alpha blocker

Indications: Chronn's Disease, Rheumatoid Arthritis 

Approval: 2008

Other Info: 

• Cimzia is a humanized Mab that does not contain the Fc portion (only the Fab portion and a segment (CH1) linked to PEG!)
• Administered SC (monthly dosing after initial therapy)

Trade Name: Simponi 

Type: Human Mab

Mechanism of Action: TNF-alpha Blocker

Indications: Ankylosing Spodylitis, Psoriatic Arthritis, Rheumatoid Arthritis 

Approval: 2009

Other Info: 

Trade Name: Stelara 

Type: Human Mab

Mechanism of Action: IL-12 and IL-23 blocker

Indications: Plaque Psoriasis 

Approval: 2009

Other Info: 

• Dual mechanism of action
• SC every 12 weeks
• Blocks IL-12 and IL-23 cytokines from binding to respective IL receptors on surface of T-cells.
• Prevents T-cell signalling (Th1 and Th17 pathways)

Trade Name: Actemra 

Type: Humanized Mab

Mechanism of Action: IL-6 receptor antagonist

Indications: Rheumatoid Arthritis

Approval: 2010

other Info: 

Trade Name: Zenapax

Type: Humanized Mab (anti-IL 2 rMab) 

Target: IL-2 receptor

Indications: Transplant Rejection

Approved: 1997

Additional Info: 

Trade Name: Simulect

Type: Chimeric (anti IL-2 rMab)

Target: IL-2 receptor 

Indications: Transplant Rejection

Approved: 1998

Additional Info: 

•Bind specifically to IL-2 receptor alpha-subunit on surface of activated T-cells.

Trade Name: Synagis

Type: Humanized Mab

Target: epitome of the F protein of RSV (epitome means short arm) 

Indications: Respiratory Syncytial Virus (RSV)

Approved: 1998

Additional Info:

• Palivizumab is a IgG1k MAb (humanized) composed of human (95%) and murine (5%) antibody sequences, with a MWT of 148 kDa.
• Directed to an epitope of the F protein of respiratory syncytial virus (RSV).
• Exhibits neutralizing and fusion-inhibitory activity against RSV.
• Indicated for the prevention of serious lower respiratory tract disease caused by RSV in pediatric patients at high risk of RSV disease.
• Administered Intramuscularly (IM)
• Protects infants for 30 days/dose

Trade Name: Lucentis

Type: Humanized Mab

Target: VEGF (Vascular endothelial growth factor -stimulates growth of new blood vessels)

 Indications: Age related Macular Degeneration

Approved: 2006

Additional Info: 

Trade Name: Tysabri

Type: Humanized Mab

Target: T-cell VLA4 receptor

Indications: Multiple Sclerosis

Approved: 2006

Additional Info: 

• is the first alpha-4 antagonist in the new selective adhesion molecule (SAM) inhibitor class. (It blocks T-cells from entering and gaining access to CNS) The drug is designed to inhibit the migration of T-cells into chronically inflamed tissue of the CNS where they may cause or maintain inflammation. 
• Natalizumab works by blocking the T-cell surface integrin and preventing immune cells from migrating through blood vessels in the brain to areas of inflammation.
• Indicated for treatment of RRMS (relapsing remitting multiple sclerosis), slow progression of disease and reduce flare-ups associated with MS.
• Also indicated for Crohn’s Disease!! Patients with moderately to severely active CD with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α.
• Interaction between the integrin a4b1 and vascular cell adhesion molecule 1 (VCAM1), which is blocked by natalizumab, is important in the entry of leukocytes, including T cells, into the central nervous system. These cells are thought to contribute to the damage of the myelin sheath and possibly the axon through several complex mechanisms.  The damage is specific to a protective barrier around the neurons, it won’t be wide spread 
• Natalizumab therapy increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. This is a fatal condition in the brain. 
• Was removed from the market because of PML but returned in 2006 with new standards from FDA. 
• Because of the risk of PML, TYSABRI® is available only through a special restricted distribution program called the TOUCH™ Prescribing Program.  (part of restriction imposed on the drug when it re-entered the market by the FDA)
• Under the TOUCH™ Prescribing Program, only prescribers, infusion centers, and pharmacies associated with infusion centers registered with the program are able to prescribe, distribute, or infuse the product.
• In addition, TYSABRI® must be administered only to patients who are enrolled in and meet all the conditions of the TOUCH™ Prescribing Program
• Cost (12 infusions/year)  30k per year

Trade Name: Thymoglobulin 

Type: Pab (polyclonal antibody) 

Target: Ig mediated T-cell Depletion by an unknown mechanism  

Indications: Induction Therapy of Transplant Patients (immediate, profound immunosuppression for approximately 2 weeks post transplant) 

Approved: -- 

Additional Info:

• It is a purified IgG –based polyclonals obtained by immunization of rabbits with human thymocytes.
• This immunosuppressive product contains cytotoxic antibodies directed against antigens expressed on human T-lymphocytes.
• In patients, T-cell depletion is usually observed within a day from initiating Thymoglobulin therapy.

Trade Name: Prednisone 

Type: small molecule (corticosteroid) 

Target: Suppress release of IL-1 and IL-6  from APC’s

(this prevents Tc-cell activation and APC communication)

[they inhibit NK-beta activation and inflammatory cytokine production] 

Indications: Maintenance therapy for transplant patients (reduce the immune system's ability to recognize and reject the foreign organ or tissue, while limiting toxicity. This is a lifelong therapy tailored for each patient) 

 Approved

Additional Info: 

Trade Name: Prograf

Type: Small Molecule (calcineurin inhibitor...cyclosporine is another but it isn't used much at all) 

Target: Inhibits calcineurin, Blocks production of IL-2 from T-cells.

 Indications: Maintenance Therapy for Transplant patients 

Approved

Additional Info: 

Trade Name: Rapamune 

Type: Small Molecule (mTOR inhibitor) 

Target: Inhibits mTOR; Blocks  IL-2-driven T-cell proliferation 

 Indications: Induction Therapy for Transplant Patients

Approved -- 

Additional Info: 

Trade Name: Cellcept

Type: Small Molecule

Target: Blocks purine synthesis and T-cell proliferation

Indications: Maintenance therapy for transplant patients 

Approved: -- 

Additional Info: 

Trade Name: Copaxone 

Type: It composed of acetate salts (L-glutamic acid, L-glysine, L-tyrosine, L- lysine) 

Target: 

•Hence, the ability of GA-specific infiltrating T-cells to express and induce the formation and release of these potent modulating cytokines may contribute to its therapeutic activity

Indications: Treatment of Multiple Sclerosis

Approved

Additional Info: 

Trade Name: Proventil, Ventolin, Proair 

Type: 

• b2-agonists (Short acting)

Target:

• Causes relaxation of the bronchial smooth muscles through stimulation of beta-2-adrenergic receptors. 

Indications: 

• Bronchodilators (b2-agonists) are the best choice for relieving sudden attacks of asthma and for preventing attacks from being triggered by exercise. THey workTo prevent asthma symptoms while exercising
• As the main treatment for mild intermittent asthma. These medications also are used to relieve sudden asthma symptoms. They do not control the inflammation 

Approved: -- 

Additional Info:

• Acts mainly in lung cells and have little effect on other organs, such as the heart. 
• Start acting within minutes, increasing airflow and making it easier to breathe.  Good for four to six hours.
• They may be taken orally, inhaled, or injected.

Trade Name: Flovent 

Type: long term anti-asthmatic medication

Target: 

• Corticosteroids resemble natural body hormones which reduce inflammation in the bronchial tubes. They also decrease the mucus made by the bronchial tubes and make breathing easier. (They are meant to block inflammation. Certain steroids can block events very early in T cell activation on a transcription level.)

 Indications: 

• When steroids are taken by inhalation for a long period, asthma attacks become less frequent as the airways become less sensitive to allergens

Approved

Additional Info:

• Usually administered by Metered Dose Inhalers (MDI) or Dry Powder Inhalers (DPI).  Used in combination with other medications.

Trade Name: Montelukast - Singulair 

Type: Leukotriene Modifiers

Target:

•  inhibit leukotriene receptors, resulting in the reduction of leukotriene-induced bronchoconstriction.
• They work by counteracting leukotrienes, substances released in the lung that cause the air passages to constrict and promote mucus secretion. Leukotriene pathway modifiers improve lung function and decrease asthma symptoms 

Indications: Asthma (work on inflammation side of the disease) 

Approved: -- 

Additional Info: Can be used in combination with steroids 

Trade Name: -- 

Type: Both are Long-acting b2-agonists (bronchodilators)

Target: :  relax smooth muscle in the bronchial tubes, allowing the tubes to remain open longer and making breathing easier.  Prevent the late phase of bronchoconstriction induced by allergen exposure.

 Indications: long term treatment of bronchospasm during asthma

Approved: -- 

Additional Info:

• Long-acting inhaled b2-agonists are indicated for use only by people who are also taking inhaled corticosteroids. They may be used in the following situations:
  • To treat moderate persistent and severe persistent asthma
  • In combination with an inhaled corticosteroid, because they enhance steroids anti-inflammatory action for controlling asthma and preventing asthma attacks
  • These work well to control asthma during exercise and while sleeping

Trade Name: --

Type: Mast Cell Stabilizer 

Target:  

• Target Mast Cells
• These medications can prevent attacks when given before exercise or when exposure to an allergen cannot be avoided. Regular use of cromolyn improves lung function and the ability to exercise. Peak expiratory flow rates are improved, and the need for short-acting b2-agonists is decreased.

Indications: Long term care of asthma 

Approved

Additional Info: 

• Initially used in children as a long term treatment to prevent asthma attacks. 
• These are safe drugs but are expensive, and must be taken regularly even if there are no symptoms!
• These medications have few side effects but many patients complain of the taste. Nausea, vomiting, and diarrhea occur, as seen in other medications, but these symptoms are rare

• Not used for acute attacks.
• 150 to 375 mg SC/ every 2 to 4 weeks (Not self-injectable)
• Expensive:  $10k to 12k per year