PHM 424 INFLAMMATORY BOWEL DISEASE
What are the monitoring parameters of methotrexate?
-CBC
-SCr
-BUN
-LFTs
What are the adverse effects of cyclosporine?
-nephrotoxicity
-neurotoxicity
What are the monitoring parameters of cyclosporine?
-SCr
-BUN
What is TPMT and its significance?
-methylating enzyme that functions to protect body from incorporating damaging purines
into DNA and RNA
-patients who have heterozygous mutations in TPMT = ~50% enzyme activity
-homozygous = no activity
-TPMT is responsible for metabolizing thiopurine drugs like azathioprine and mercaptopurine
-patients with mutations/low TPMT are at high risk of myelosuppression
-assess TPMT mutations before starting ANY patient on azathioprine or 6-mercaptopurine
Infliximab
-Remicaid
-IV IgGI chimeric monoclonal antibody that binds to TNFa and inhibits anti-inflammatory
effects
-lyses activated T cells and macrophages, induces T-cell apoptosis
,Adalimumab
-Humira
-SC IgGI antibody to TNFa (fully humanized)
Certolizumab pegol
-Cimzia
-SC humanized pegylated Fab fragment directed against TNFa
Golimumab
-Simponiaria
-SC antibody against TNFa
Natalizumab
-inhibits leukocyte adhesion and migration by targeting a3 subunit of integrin
-generally not used due to risk of progressive multifocal leukoencephalopathy (PML)
Vedolizumab
-Entyvio
-IV
-inhibits leukocyte adhesion and migration by targeting a4B7 subunit of integrin
-specificity reduces/eliminates risk of PML
Ustekinumab
-Stelara
-IV for first dose, then SC
-blocks action of IL21 and IL23 by binding to p40 protein subunit
-approved in patients who failed immunomodulators or corticosteroids, but have not
received anti-TNF therapy or have tried and failed anti-TNF therapy
Tofacitinib
, -Xeljanz
-PO tablet
-inhibits intracellular Janus kinases
-approved for patients who are unresponsive to TNFa inhibitors
-caution: DDI with CYP3A4 and 2C19 inhibitors; GI perforation reported with XR formulation
Ozanimod
-PO capsule = Zeposia
-SIP1 and SIP5 receptor modulator
-currently approved in US for MS, studies in IBD are being conducted
What are the adverse effects of TNFa inhibitors?
-infusion related reactions (infliximab)
-infection
-heart failure
-optic neuritis
-demyelination
-injection site reactions
What are the monitoring parameters for TNFa inhibitors?
-BP, HR (infliximab)
-neurologic exam
-mental status
-trough concentrations (infliximab and adalimumab)
-antidrug antibodies
-negative PPD for TB and viral serologies needed before starting
(Men/Women) ______ more commonly experience Crohn's Disease
- Women
(Men/Women) ______ more commonly experience Ulcerative Colitis
- Men
What are the monitoring parameters of methotrexate?
-CBC
-SCr
-BUN
-LFTs
What are the adverse effects of cyclosporine?
-nephrotoxicity
-neurotoxicity
What are the monitoring parameters of cyclosporine?
-SCr
-BUN
What is TPMT and its significance?
-methylating enzyme that functions to protect body from incorporating damaging purines
into DNA and RNA
-patients who have heterozygous mutations in TPMT = ~50% enzyme activity
-homozygous = no activity
-TPMT is responsible for metabolizing thiopurine drugs like azathioprine and mercaptopurine
-patients with mutations/low TPMT are at high risk of myelosuppression
-assess TPMT mutations before starting ANY patient on azathioprine or 6-mercaptopurine
Infliximab
-Remicaid
-IV IgGI chimeric monoclonal antibody that binds to TNFa and inhibits anti-inflammatory
effects
-lyses activated T cells and macrophages, induces T-cell apoptosis
,Adalimumab
-Humira
-SC IgGI antibody to TNFa (fully humanized)
Certolizumab pegol
-Cimzia
-SC humanized pegylated Fab fragment directed against TNFa
Golimumab
-Simponiaria
-SC antibody against TNFa
Natalizumab
-inhibits leukocyte adhesion and migration by targeting a3 subunit of integrin
-generally not used due to risk of progressive multifocal leukoencephalopathy (PML)
Vedolizumab
-Entyvio
-IV
-inhibits leukocyte adhesion and migration by targeting a4B7 subunit of integrin
-specificity reduces/eliminates risk of PML
Ustekinumab
-Stelara
-IV for first dose, then SC
-blocks action of IL21 and IL23 by binding to p40 protein subunit
-approved in patients who failed immunomodulators or corticosteroids, but have not
received anti-TNF therapy or have tried and failed anti-TNF therapy
Tofacitinib
, -Xeljanz
-PO tablet
-inhibits intracellular Janus kinases
-approved for patients who are unresponsive to TNFa inhibitors
-caution: DDI with CYP3A4 and 2C19 inhibitors; GI perforation reported with XR formulation
Ozanimod
-PO capsule = Zeposia
-SIP1 and SIP5 receptor modulator
-currently approved in US for MS, studies in IBD are being conducted
What are the adverse effects of TNFa inhibitors?
-infusion related reactions (infliximab)
-infection
-heart failure
-optic neuritis
-demyelination
-injection site reactions
What are the monitoring parameters for TNFa inhibitors?
-BP, HR (infliximab)
-neurologic exam
-mental status
-trough concentrations (infliximab and adalimumab)
-antidrug antibodies
-negative PPD for TB and viral serologies needed before starting
(Men/Women) ______ more commonly experience Crohn's Disease
- Women
(Men/Women) ______ more commonly experience Ulcerative Colitis
- Men
