Modulating Drugs Flashcards
Anti-CTLA4
Iplimumab
Advanced melanoma
Increase T cell response
Anti-PD1
Pembrolizumab
Nivolumab
Advanced Melanoma
Increase T cell response
Alkylates gunaine base of DNA
Cyclophosphamide
Affects B cells > T cells
Indications
Multisystem connective tissue disease or vasculitis with severe end-organ involvement
eg GPA (Wegener’s granulomatosis), SLE
Anti-cancer agent
Blocks de novo purine (eg adenine, guanine) synthesis
Azathioprine
Indications
Transplantation
Auto-immune disease
Auto-inflammatory diseases, eg Crohn’s, ulcerative colitis
Blocks de novo nucleotide synthesis
Mycophenolate mofetil
Prevents T>B cell proliferation
Major Indications
Widely used in transplantation as alternative to azathioprine
Also used in auto-immune diseases and vasculitis as alternative to cyclophosphamide
Side effect of Progressive multifocal leukoencephalopathy (JC virus)
Mycophenolate Mofetil
Indications for plasmapheresis
Severe antibody-mediated disease
Goodpastures syndrome
Severe acute myasthenia gravis
Severe vascular rejection
Calcineurin inhibitors
Cyclosporin
Tacrolimus
Prevents IL-2 upregulation
Use post-transplant
Dysmorphism
Cyclosporin
JAK inhibitor antibody
Tofacitinib (inhibits cell signalling)
Rheumatoid Arthritis
PDEF 4 inhibitor antibody
Apremilast (inhibits cell signalling)
Psoriasis
Psoriatic arthritis
Neutropenia particularly if TPMT low
Azathioprine
Infertility
Cyclophosphamide
Inhibits T cell migration but may only be used in highly active remitting/relapsing MS
Natalizumab (Anti-a4 integrin
Inhibits T cell activation and is effective in rheumatoid arthritis
Abatacept (CTLA4-Ig fusion protein)
Depletes B cells and is effective in treatment of B cell lymphomas and rheumatoid arthritis
Rituximab (Anti-CD20)
Inhibits function of lymphoid and myeloid cells and used in management of rheumatoid arthritis
Tocilizumab (Anti-IL6 receptor)
Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Basiliximab (Anti-IL2 receptor)
Anti-Thymocyte globulin
Anti-CD3
Removes T cells
Allograft rejection
Daily IV infusion
Anti-CD25
Basiliximab
Inhibits T cell proliferation
Prophylaxis in organ transplant
IV pre and post surgery
CTLA4-Ig fusion
Abatacept
Prevents T cell activation
Rheumatoid arthritis
IV 4 weekly
Subcut weekly
Anti-CD20
Rituximab
Removes mature B cells
Lymphoma
SLE
Rheumatoid arthritis
2 doses every 6 months IV
Anti-alpha4 integrin
Natalizumab
Reduce T cell migration
Highly active relapsing MS
Crohn’s
IV every 4 weeks
Anti-CD11a
Efalizumab
Inhibits T cell migration
Psoriasis
causes PML, now withdrawn
Anti-IL-6R
Tocilizumab
Reduces activation of: Macrophages T cells B cells Neutrophils
Castleman’s
Rheumatoid arthritis
Anti-TNFa Antibodies
Infliximab
Adalimumab
Certolizumab
Golimumab
Indications and dosing
- Rheumatoid arthritis
- Ankylosing spondylitis
- Psoriasis and psoriatic arthritis
- Inflammatory bowel disease
Subcutaneous or intravenous
TNFa antagonist = TNF receptor p75-IgG fusion protein
Etanercept
Indications and dosing
- Rheumatoid arthritis
- Ankylosing spondylitis
- Psoriasis and psoriatic arthritis
- Subcutaneous weekly
Action
- Inhibits TNFa and TNFb
Antibody to p40 subunit of IL-12 and IL-23
Ustekinumab
Indications and dosing
- Psoriasis, psoriatic arthritis
- Subcutaneous every 12 weeks
Action
Inhibits IL-12 and IL-23
Antibody to IL17 A
Secukinumab
Indications and dosing
Psoriasis and psoriatic arthritis
Ankylosing spondylitis
SC load and then monthly
Action
Inhibits IL-17A
Antibody directed at RANK ligand
Denosumab
Indications and dosing
Osteoporosis
Subcutaneous every 6 months
Action
Inhibits RANK mediated osteoclast
differentiation and function
Toxicity
Infection
- Avascular necrosis of jaw
Treatment options include inhibition of IL6, TNF alpha and depletion B cells
Rheumatoid arthritis
Treatment options include inhibition of IL12/23, TNF alpha and IL17A
Psoriasis
Treatment options include inhibition of RANK ligand
Osteoporosis
