Lecture 13: Treatment for IBD Flashcards by Liz Pennington

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

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What are the four 5-ASA agents used for treating UC?

Sulfasalazine*
Mesalamine
Olsalazine*
Balsalazide*

* indicates the drug is converted to mesalamine

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What are the structural ingredients of Sulfasalazine?

Sulfapyridine + 5-ASA

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What are the structural ingredients of Mesalamine?

Single 5-ASA

*Think ‘M’ for mono-

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What are the structural ingredients of Olsalazine?

2 molecules of 5-ASA

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What are the structural ingredients of Balsalazide?

Inert carrier + 5-ASA

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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

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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

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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)

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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!)

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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

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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

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TNF-α inhibitors to be used in the treatment of IBD only after what?

AFTER inadequate response to conventional or immunosuppressant therapy

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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

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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*

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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?

Ustekinu**mab** ---\> **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