IBD Therapeutics Flashcards
What are the ASAs for IBD
sulfasalazine, mesalamine
What steroids are used for IBD
local and systemic
what are the immunomodulators used for IBD
azathioprine, mercaptopurine, cyclosporine, methotrexate
what are the anti-tnf-a agents used in IBD
infliximab, adalimumab, certolizumab, golimumab
what are the other anti inflammatory agents for IBD
natalizumab, vedolizumab, ustekinumab
what is the active component of sulfasalzine
5-ASA
exerts actions locally
mesalamine is absorbed where in the GI
rapidly absorbed in small intestine but not colon
formulations of mesalamine
topical
suppository
oral
ADRs of sulfasalazine
N/V, headache, anorexia, rash, anemia, hypersensitivity
what is the major DDI with sulfasalazine
antiplatelet/anticoag/NSAIDs all may increase bleeding risk
ADRs of mesalamine
more tolerated than sulfasalazine
N/V, headache, diarrhea, rash
DDI with mesalamine
antiplatelet/anticoag/nsaids all may increase bleeding risk
PPI, H2RA, antacids could all influence release of drug
Budesonide class and MOA
corticosteroids and anti inflammatory
what is the budesonide formulation for IBD
PO in CR formulation
how long can you use corticosteroids in IBD
8-16 weeks
what are the DDIs with budesonide
CYP3A4 inhibitors (ketoconazole, grape fruit juice)
what are the ADRs of all corticosteroids
short term: hyperglycemia, gastritis, mood changes, increased BP
long term: aseptic necrosis, cataracts, obesity, growth failure, HPA suppression, osteoporosis
what other corticosteroids besides budesonide can be used for IBD
oral prednisone or prednisolone
IV methylprednisolone or hydrocortisone
can be used for disease flares or induction of remission
when to use azathioprine (AZA) and mercaptopurine (MP, 6-MP)
Reserved for patients who fail 5-ASA or pts who are refractory to/dependent on steroids
can you use AZA or MP for induction?
no but it can maintain remission
can you use AZA/MP with other drugs
yes
when can you see the benefit of AZA/MP
weeks to months
What are the ADRs of AZA and 6-MP
N/V/D, anorexia, stomatitis
bone marrow suppression
hepatotoxicity
fever, rash, arthralgia, pancreatitis
what is the monitoring for AZA/MP
TMPT must be taken prior to start
CBC
LFTs
when to use cyclosporine
inducing remission in patients with refractory IBD
not an option for long term use
ADRs of cyclosporine
nephrotoxicity
neurotoxicity
HTN, hyperlipidemia, hyperglycemia
GI upset, hirsutism
monitoring of cyclosporine
BP, BUN/SCr, LFTs, trough concentration
what are the DDIs with cyclosporine
increase conc: azoles, anti-fungals, macrolide antibiotics, CCBs, grapefruit
decrease conc: phenytoin, rifampin
When to use methotrexate
crohn’s disease for maintenance
what are the ADRs of methotrexate
bone marrow suppression (add folic acid)
N/V/D, stomatitis, mucositis
cirrhosis, hepatitis, fibrosis
hypersensitivity pneumonitis
derm effects
teratogenic (need contraception)
when is methotrexate contraindicated
pregnancy
pleural effusions
chronic liver disease
immunodeficiency
blood issues
ClCr < 40 ml/min
monitoring for methotrexate
CXR
CBC
SCr
LTFs
what is the class and indication for infliximab (remicade)
anti TNF-alpha
CD and UC
what is the class and indication for adalimumab (humira)
anti TNF-alpha
CD and US
what is the class and indication for golimumab (simponi)
anti TNF-alpha antibody
UC
what is the class and indication for certolizumab pegol (Cimzia)
anti-TNF alpha
CD
what is the class and indication for Natalizumab (Tysabri)
anti alpha integrin
CD
what is the class and indication for vedolizumab (entyvio)
anti a4B7 integrin
UC and CD
what is the class and indication for ustekinumab (stelara)
IL-12 and IL-23 antagonist
CD and UC
what is the class and indication for risankizumab-rzaa (skyrizi)
IL-23 antagonist
CD and UC
what is the class and indication for mirikizumab (Omvoh)
IL-23 antagonist
UC
what is the class and indication for tofacitinib (xeljanz)
oral JAK inhibitor
UC
what is the class and indication for upadacitinib (Rinvoq)
oral JAK 1 inhibitor
UC and CD
What is the class and indication for ozanimod (Zeposia)
oral S1P receptor modulator
UC
what is the class and indication for estrasimod (Velsipity)
oral s1p receptor modulator
UC
What are the class ADRs of anti-TNF-alpha
-increased risk of infection
-CI of live vaccines during tx and 3 months after
-injection site rxn
-risk of malignancy/lymphoma
-demyelinating disease
-exacerbation of CHF
baseline monitoring for Anti-TNF-alpha
-CXR, PPD
-infection
-UA
-CBC
-SCr, lytes
-LFTs
-Hep B, C
maintenance monitoring for anti-TNF-alpha
infections
UA
CBC
SCr, Lytes
LFTs
inflammatory markers
when to use infliximab
mod-sev CD and UC
induction and maintenance
how to prevent development of ADAs in biologics
combine with azathioprine, but could increase ADRs
when to use adalimumab
mod-sev CD and UC
induction and maintenance therapy
when to use golimumab
mod-sev UC
induction and maintenance
when to use certolizumab
mod-sev CD
induction and maintenance
when to use natalizumab
CD
induction and remission
used in pts who fail or do not tolerate TNF-alpha
when do d/c natalizumab
d/c if not working
what is associated with natalizumab that is severe
Progressive Multifocal Leukoencephalopathy (PML)
when to use vedolizumab
UC and CD
induction and remission
ADR of vedolizumab
biologic ADRs
less association with PML
TDM possible
when to use ustekinumab
CD and UC
induction (IV) and maintenance (SQ)
severe ADR associated with ustekinumab
carcinomas of the skin (get regular skin exams)
when to use risankizumab (Skyrizi)
mod-sev CD and UC
induction (IV) and maintenance (SQ)
ADRs of risankizumab
biologic ADRs
increase of LFTs
increase of lipids
when to use mirikizumab
UC
induction and maintenance
ADRs of mirikizumab
biologic ADRs
increase of LFTs and lipids
Why should TDM be tested
determines conc and drugs and ADA in body
consider doing TDM if loss of treatment response
If there is subtherapeutic drug levels and detectable ADA, what is the cause and what should you do?
An immune mediated PK issue change to alternate drug within same class
If there is subtherapeutic drug levels and undetectable ADAs, what is the cause and what should you do?
Non-immune mediated PK issue
increase the dose
If there are therapeutic drug levels and detectable ADAs, what is the cause and what should you do?
Either a false positive or mechanistic failure
repeat TDM or switch to out of class biologic
If there are therapeutic drug levels and undetectable ADAs, what is the cause and what should you do?
Mechanistic failure
Switch to out of class biologic agent
when to use tofacitinib
UC only for pts who have inadequate response to or intolerant to TNF blockers
what are ADRs for tofacitinib
common: diarrhea, elevated cholesterol, headache, shingles, rash
rare: malignancy, infection, neutropenia
black box warning for tofacitinib
increased mortality for RA patients 50+ with at least one CV risk factor
increased thrombosis for those patients
when to use upadacitinib
UC and CD for pts who have inadequate response to or intolerant to TNF blockers
black box warning for upadacitinib
same warning as tofacitinib
ADR for upadacitinib for young women
potentially teratogenic, excreted in breast milk
when to use ozanimod
mod-sev active UC
used alone
what is the dosing catch with ozanimod
if a dose is missed in the first two weeks of tx, reinitiate titration regimen
what are the CI for ozanimod
MACE in last 6 months
mobtiz type II
severe or untreated sleep apnea
taking MAO inhibitor
what are the ADRs of ozanimod
increased risk of infection
bradycardia/AV conduction delays
when to use estrasimod
mod-sev UC
what are CI to estrasimod
MACE in last 6 months
cardiac conduction abnormalities
