Immunomodulators

 Drug Mechanism of Action Side Effects
 
Interferon
Antiviral and antiproliferative properties
SE: flu-like symptoms, leukopenia,
hepatotoxicity
 
Imiquimod,
Resiquimod
Binds TLR7 and induces TNFα, IL-6, and IFNα; antiviral and antitumor properties
Topical formulation; stimulates both innate
and adaptive immune system
   
 
Table 7-5 Biologically Engineered Immunomodulators
 NameRoute/CategoryMechanism of ActionOthers
 
Etanercept
(Enbrel)
Subcutaneous

Category B
TNFα inhibitor: fusion protein consisting of TNFα receptor linked to Fc portion of human IgG1; binds free (soluble) TNFα
Avoid live vaccines

SE: multiple sclerosis, + ANA and LE symptoms, worsening of CHF, serious infections, TB reactivation, malignancy
 
Infliximab
(Remicade)
Intravenous

Category B
TNFα inhibitor: chimeric monoclonal Ab against TNFα (mouse Fv/human IgG1); binds soluble and membrane-bound TNFα
Avoid live vaccines

Category B SE: infusion reaction, other side effects similar to etanercept
 
Adalimumab
(Humira)
Subcutaneous

Category B
TNFα inhibitor: fully human monoclonal Ab against TNFα; binds soluble and membrane-bound TNFα
Same as other TNFα inhibitors
 
Golimumab
(Simponi)
(CNTO 148)
Subcutaneous

Category B
Same as other TNFα inhibitors
 
Certolizumab pegol (Cimzia)
Subcutaneous

Category B
TNFα inhibitor: human monoclonal Ab against TNFα; PEGylated Fab’ fragment of human TNFα monoclonal Ab
Same as other TNFα inhibitors
 
Efalizumab
(Raptiva)
Subcutaneous

Category C
Humanized form of murine Ab against CD11a, which blocks LFA1 interaction with CAM1; blocks lymphocyte extravasation
Removed from market in 2009 due to risk of progressive multifocal leukoencephalopathy (PML)
 
Alefacept
(Amevive)
Intramuscular

Category B
Fully human dimeric fusion protein: extracellular domain of LFA3 fused with human Fc portion of IgG1; inhibits CD2/LFA3 interaction thus blocking T-cell activation
Monitor CD4 T-cell count weekly or every other week
 
Ustekinumab
(Stelara)
(CNTO 1275)
Subcutaneous

Category B
IL-12/IL-23 inhibitor: human IgG1 monoclonal antibody against p40 subunit of IL-12 and IL-23 cytokines (both cytokines share same p40 subunit)
SE comparable to TNFα inhibitors
 
Briakinumab
(ABT-874)
Subcutaneous
IL-12/IL-23 inhibitor
Currently under investigation
 
AIN-547
Monoclonal antibody against IL-17
Currently under investigation
        
 
   


Figure 7.3 A: TNFα inhibitors B: IL-12/IL-23 inhibitor
Figure 7.3 A: TNFα inhibitors B: IL-12/IL-23 inhibitor