What are the "Mab" (monoclonal antibody) and "Cept" (fusion) drugs on our list?
"Mab"s: infliximab (Remicaid), adalimumab (Humira), tocilizumab (Actemra), rituximab (Rituxan)
"Cept"s: etanercept (Enbrel), abatacept (Orencia)
What are some common side effects of biologics?
Activation of latent TB (test for and treat TB first)
Infection site reactions
What are the indications for Etanercept?
Rheumatic syndromes: decreases new erosions in joints
What is the MOA of etanercept?
Fusion protein: fusion of TNF alpha receptor and Fc domain of IgG1
Acts as a decoy receptor for TNF alpha so it cannot do its work
What is the ADME for etanercept?
Administered SC q 2 weeks
often combined with non-biologic DMARDS
What are the side effects of etanercept?
increased antinuclear antibodies in 98% (can lead to SLE)
activation of latent TB
infection site reactions
NOTE: less immunogenic (patients less likely to develop antibodies to etanercept than other TNF alpha blockers)
What are the indications for infliximab and adalimumab?
What is the MOA of infliximab and adalimumab?
Which is chimeric human/mouse?
Monoclonal antibodies that bind TNF alpha and down regulate T-cells and macrophages
Infliximab is chimeric human/mouse
Adalimumab is all human
What is the ADME for infliximab (Remicaid)?
Administation: IV q 8 wks, often in combo with nonbiologic DMARDS
Patients often develop antibodies to Infliximab.
Coadministation with methotrexate prevents this.
What are the side effects of infliximab?
Basal cell and squamous cell skin cancer
Nausea, HA, sinusitis, rash, cough
Injection site reaction
Activation of latent TB
What are the side effects of adalimumab (Humira)?
Basal and squamous skin cancer
Lupus-like Sx (rare)
Infection site reaction
What is the MOA of Tocilizumab?
that inhibits binding of IL-6 to its receptor
thereby blocking activation of JAK-STAT pathway,
decreasing transcription of pro-inflammatory proteins
What are the indications for tocilizumab?
RA patients who are unresponsive to TNF alpha inhibitors
What is the ADME for tocilizumab?
Administration: IV q 4-6 weeks
How does Tocilizumab affect the metabolism of other medications?
IL-6 suppresses several CYPs in the liver,
so inhibition of IL-6 results in induction of CYPs
and increased metabolism of medications.
Increase dosages accordingly.
What are the side effects of tocilixumab?
Activation of latent TB
What is the MOA of rituximab?
Humanized monoclonal antibody with selectivity for CD-20 on B-cells
Results in B-cell depletion
What are the indications for rituximab?
RA patients unresponsive to TNF alpha inhibitors
Chronic Lymphocytic Leukemia (CLL)
What is the ADME of rituximab?
Administration: IV q 2 weeks with methotrexate q 6 mo
What are the side effects of rituximab?
Serious infections (Hep B reactivation, bacterial, fungal, not TB)
First dose infusion reaction (Tx with glucocorticoids)
Some cardiac events and death reported
C/I re pregnancy: wait 6 mo prior to conception!
What is the MOA of abatacept?
Neutralizes co-stimulatory ligand CD80/86 on APCs
preventing binding to CD28 on T cells
preventing T cell activation
What are the indications for abatacept?
RA refractory to TNF alpha inhibitors
What is the ADME for abatacept?
Administration: IV on day 1, wk 2, wk 4, then q 4 wks
What are the side effects of abatacept?
Serious infections 3%: no live vax til 3 mo after D/C
Lung cancer and lymphoma
Respiratory problems in patients with COPD
Which biologics would you prescribe for IBD?
infliximab or adalimumab
Which biologics would you prescribe for NonHodgkin's Lymphoma?
Which biologics would you prescribe for Chronic Lymphocytic Leukemia?
Which biologics are TNF alpha inhibitors?
Which biologics are IL-6 inhibitors?
TocILizumab (it has an IL in its name)
Which biologics are B-cell depleters?
Which biologics block costimulation of T-cells?
What is the MOA of methotrexate?
Folic acid analog
that inhibits the formation of cofactors for synthesis of:
purine, amino acid and thymidylate
What are the indications for methotrexate?
Combined with biologics
to inhibit antibody formation against them
What is the major side effect of methotrexate?