bDMARDS Flashcards
What does bDMARDS stand for
biologic disease modifying anti rheumatic drugs
what are bDMARDs approved for
approved for use against RA
- can be TNFa antagonists or work on other targets
give examples of bDMARDs that are TNFa antagonists
etanercept, infliximab, adalimumab
give examples of bDMARDs that act on other targets
rituximab- CD20
what do the TNFa inhibitors target
target soluble TNFa or cellular TNFa receptors
describe the structures of adalimumab, infliximab and golimumab
- these 3 TNFa inhibitors are structurally all produced as recombinant, glycolated, full length IgG monoclonal antibodies
- in contrast to etanercept and certolizumab pegol, these drugs are all full length Mabs
how do adalimumab, infliximab and golimumab work
- like etanercept and certolizumab pegol, they bind to TNFa and prevent it signalling through its cellular TNF receptors, TNFR1 and TNFR2
what is the structure of infliximab
- a purified recombinant chimeric human mouse IgG Mab
- mouse heavy and light chain variable regions and human heavy and light chain constant regions
what does infliximab have a greater risk of
greater risk of inducing anti drug antibodies than adalimumab and golimumab
what is the structure of adalimumab
- first fully human mab approved for use by FDA
what is the structure of golimumab
fully human mab
what is humira
human monoclonal antibody in RA
What is the mechanism of action of monoclonal antibodies in RA
- neutralise TNFa by binding with high affinity to both soluble and transmembrane TNFa, plus TNF bound to the soluble form of TNF receptors
what is the primary mechanism of action of monoclonal antibodies
blocking cytokine signalling
what is the secondary mechanism of action of monoclonal antibodies
1.Fc domain binds to FcY receptors on immune cells, signalling them for destruction by killer cells through antibody dependent cellular cytotoxicity (ADCC)
2. or, Fc domain binds to fix complement, activating complement mediated lysis
what is certolizumab pegol (cimzia)
a modified antibody fragment
explain how certolizumab pegol works
- it is composed of the antibody binding fragment (Fab) of a humanised monoclonal antibody against TNF
- this is conjugated to polyethylene glycol which:
- increases its plasma half life to 14 days, allowing fortnightly sc use
- increases bioavailability
- increases drug stability and retention time by reducing renal clearance, proteolysis and immunogenicity - like other TNF antagonists, cimzia binds to soluble and membrane bound TNFa, inhibiting its proinflammatory actions
what are the benefits of cimzia
- has no Fc domain, so cannot fix complement or trigger ADCC
- makes it less immunogenic than full length mabs, so reduces immune related side effects - doesn’t appear to cross placenta so can be used by pregnant and breastfeeding women