Lecture 13: Treatment for IBD Flashcards
What are the 2 MOA for the 5-ASA agents used for UC?
- Inhibition of PG and LT production via arachidonic acid pathway
- Reduction in PMN and macrophage chemotaxis
What are the four 5-ASA agents used for treating UC?
- Sulfasalazine*
- Mesalamine
- Olsalazine*
- Balsalazide*
* indicates the drug is converted to mesalamine
What are the structural ingredients of Sulfasalazine?
Sulfapyridine + 5-ASA
What are the structural ingredients of Mesalamine?
Single 5-ASA
*Think ‘M’ for mono-
What are the structural ingredients of Olsalazine?
2 molecules of 5-ASA
What are the structural ingredients of Balsalazide?
Inert carrier + 5-ASA
How does the formulation of 5-ASA as a rectal suppository vs. rectal enema differ in the distribution of the drug in the colon for treatment?
- Enemas may reach the splenic flexure
- Suppository may reach the upper rectum
What are the contraindications for using 5-ASA drugs in treating UC?
- ALL 5-ASA’s are contraindicated in patients allergic to aspirin (ASA)
- Sulfasalazine is contraindicated in sulfonamide-allergic pts
What are the indications for using 5-ASA drugs in the treatment of UC (i.e., severity of disease and patients in which state of disease)?
What are the 2 exceptions?
- Indicated for active dz and maintanence in pts w/ Mild-to-Moderate UC
- Olsalazine used only for maintenance of remission
- ‘B’alsalazide use only for ‘A’ctive disease (‘A’ and ‘B’ go together)
What are the 4 TNF-α inhibitors used for the treatment of IBD?
There are 2 that are only used for UC or CD, which are they?
- Adalimumab (CD and UC)
- Golimumab (UC only!)
- Infliximab (CD and UC)
- Cetrolizumab (CD only!)
What is the MOA of the TNF-α inhibitors used in the treatment of IBD?
Binds to and neutralizes TNF-α mediated pro-inflammatory cell signaling, ultimately blocking leukocyte migration to sites of inflammation
What are adverse effects of using TNF-α inhibitors for IBD?
Because of these what must be done before using?
- Infections –> Must do TB testing prior to therapy!
- Hepatotoxicity –> increased enzymes (get LFT prior to)
- Headache/arthralgias/fatigue
- Rare = EM, SJS, TEN (dermatologic conditions) and malignancies
TNF-α inhibitors to be used in the treatment of IBD only after what?
AFTER inadequate response to conventional or immunosuppressant therapy
What are the indications for using TNF-α inhibitors as a treatment of IBD (i.e., severity of dz and disase state of pt)?
- Can be used for active dz or maintenance
- Pts with moderate-to-severe
Of the TNF-α inhibitors for IBD which is the only one that can be administered via IV for a maintenance does and how often?
Infliximab infusion every 8 weeks
*The ‘I’ can remind you of IV*
Which 5-ASA agent used for UC has mutliple routes of administration and what are they?
- Mesalamine (single 5-ASA)
- pH-dependent released in terminal ileum and colon
- Time-dependent; controlled release
- Rectal enema
- Rectal suppository
What are the α-4 integrin inhibitors used for IBD and differentiate which is for UC, CD, or both.
- Vedolizumab (UC and CD) –> think ‘V’ = versatile
- Natalizumab (CD only)
What is the MOA of the α-4 integrin inhibitors used in the tx of IBD?
Limits intergrin’s-associated cell adhesion and subsequent transendothelial migration of leukocytes to site of inflammation
What is a specific adverse effect related to Natalizumab used for treating IBD?
Progressive multifocal leukoencephalopathy (PML)
What are the 3 risk factors for PML associated with Natalizumab in the treatment of CD?
1) Treatment >2 years
2) Prior immunosuppressant treatment
3) anti-JC virus (JCV) antibodies
Before using natalizumab for the treatment of CD, what kind of screening is recommended due to risks of PML?
- Gadolinium-enhanced MRI of the brain
- When indicated CSF analysis for JC viral DNA
What are the indications for using the α-4 integrin inhibitors for treatment of IBD (i.e., severity of dz and disease state of patient)?
- Used for active dz and management
- Moderate-to-severe IBD
Using α-4 integrin inhibitors for the treatment of IBD should only be done after what?
Inadequate response to conventional or TNF-α therapy
What is the route of administration and how does the maintenance dosing for Natalizumab vs. Vedolizumab differ?
- Natalizumab –> IV every 4 weeks
- Vedolizumab –> IV every 8 weeks
Which agent is an IL-12/23 inhibitor used for IBD and which type specifically?
Ustekinumab —> CD
What is the MOA for the IL-12/23 inhibitor, Ustekinumab, used in the treatment of CD?
- Binds P40-subunit of IL-12/23 blocking activation and differentiation of naive T cells and activation of NK cells
- Inhibits production of pro-inflammatory cytokines
Which serious adverse effect exists with IL-12/23 inhibitors, specifically Ustekinumab, used in the treatment of CD?
Infections –> TB test needed pre-therapy!
What is the indication for using Ustekinumab for CD (i.e., severity of dz and state of disease in pt)?
- Indicated for active dz and maintenance
- Moderate-to-severe CD
When would it be appropriate to use Ustekinumab for the treatment of CD (i.e., only after what)?
Pts intolerant or inadequate response (resistant) to conventional, immune modulators, steroids or TNF-α therapy
*NEVER in conjunction w/ these agents
Which routes of administration exist for Ustekinumab and what is the dosing schedule for each?
- IV as a single infusion for induction
- SQ every 8 weeks for maintenance
What is the Janus Kinase (JAK) inhibitor used for treatment of IBD?
Which form of IBD specifically?
- Tofacitnib
- UC only!
What are some of the adverse effects of the JAK-inhibitor, Tofacitinib used for UC?
- Lymphopenia/Lymphocytosis
- Neutropenia/Anemia
- Fatigue
- Increases in LDL and HDL
What is the indication for using Tofacitinib in the tx of UC (i.e., severity of dz and disease state of patient)?
- Used for active dz and maintenance
- Moderate-to-severe UC
What is the recommendation for using Tofacitinib with other drugs when treating UC?
Concomitant use of biologic therapies or potent immunosuppressant’s is NOT recommended
What is the route of administration for Tofacitinib and the dosing schedule?
Administered PO 2x/day (BID)
What are the indications for using steroid agents in treating IBD?
Can they be used for maintenance of remission?
How should they be dosed if used?
- Acute and/or severe UC and CD uncontrolled by other conventional meds
- NOT for maintenance of remission unless absolutely required (steroid-dependent)
- Use the LOWEST dose for shortest duration possible
