Drugs for Autoimmune Diseases Flashcards
- Fusion protein: extracellular domain of CTLA-4 binds to Fc portion domain of human IgG1
Mech: Blockade of co-stimulation by preventing CD80/86 (from APC cells) from binding CD28 (on T cells)
Clinical use: Rheumatoid arthritis refractory to TNF-alpha inhibitors
Adverse:
- serious infection (3%)
- cancer: Lung cancer and lymphoma
Contraindications:
- COPD
- TB
Abatacept
Mech: TNF-alpha inhibitor, preventing it from binding to its receptor
- a fusion protein: TNF-alpha receptor linked to Fc portion of human IgG1
- acts like soluble TNF-alpha receptor
- binds extracellularly to secreted TNF-alpha, preventing TNF-alpha from binding on cellular receptors
Clinical use:
- Many rheumatic syndromes
- often used in combination with DMARDs: Methotrexate, Azothioprine, Cyclosporine, Hydroxycholorquine
Benefits:
- less immunogenic than other TNF-alpha inhibitors
- No increase in malignancies
Drawback: ineffective against Ulcerative Colitis
Adverse:
- activation of latent TB
- increased risk of opportunistic infections
- Injection site reactions
Etanercept
Mech: TNF-alpha inhibitor, preventing it from binding to its receptor
- Chimeric monoclonal antibody: 75% human, 25% mouse
- Binds both soluble and membrane-bound forms of TNF-alpha
Clinical use:
- Rheumatoid syndromes
- Ulcerative colitis
- Crohn’s disease
- Used in combination with DMARDs: e.g., methotrexate
Benefit:
- opportunistic infections are more rare
Drawback: development of antibodies to infliximab
- prevent by co-admin with methotrexate
Adverse:
- activation of latent TB
- May have increased incidence of lymphomas
- Infusion site reaction
- Upper resp infections
- Nausea, headache, rash, sinusitis, cough
Infliximab
Mech: B cell depleter
- humanized anti-CD20 monoclonal antibody
- prevents production of autoantibodies by B-cells
- prevents co-activation of T-cells by B-cells
Clinical use: RA in patients refractory to TNF-alpha inhibitors
- often given in combination with methotrexate
Adverse:
- Serious viral infections (2%): e.g., Hep B reactivation
- Infusion reactions
- May harm fetus (think “Anti-B”): Women should avoid having baby up to 1 year after after treatment
Rituximab
- a monoclonal antibody that acts as an IL-6 receptor antagonist, thereby blocking cell’s ability to produce proinflammatory proteins
Clinical use: Rheumatoid arthritis in patients unresponsive to TNF-alpha inhibitors
Adverse:
- inhibition of IL-6 (a CYP repressor) results in de-repression of CYP, speeding up metabolism of drugs; may need to increase levels of drugs
- Reactivation of TB
- Increase infections
- GI perforation
- Elevated serum transaminase levels
- Neutropenia, thrombocytopenia
Tocilizumab
Mediates inflammation
- acts as chemoattractant and activator of other cytokines
- high levels in RA joints
TNF-alpha
- Anti-TNF-alpha
- Anti-T and B cell directed therapy
- Co-stimulation Inhibitors: Prevent CD80/86 on antigen presenting cells from binding CD28 on T cells
Immunosuppressant Mechs for Autoimmune drugs
in the liver, it suppresses the expression of CYP enzymes
- net effects: slows metabolism of drugs
IL-6
