IBD Pharmacology

Question 1

Classes of drugs used for UC

Answer 1

5-ASA
JAK inhibitors
TNF-alpha inhibitors
Alpha-4 integrin inhibitors

[steroids, immune modulators, and abx are also utilized as first-line therapy but not officially indicated]

Question 2

Classes of drugs used for Crohns

Answer 2

IL-12/23 inhibitors
TNF-alpha inhibitors
Alpha-4 integrin inhibitors

[steroids, immune modulators, and abx are also utilized as first-line therapy but not officially indicated]

Question 3

MOA of 5-ASA agents

Answer 3

Inhibition of prostaglandin and leukotriene production via arachidonic acid pathway [inhibits enzymes COX and LIPOX] —> reduction in PMN and macrophage chemotaxis

[may also inhibit activation of NFkB, thus regulating transcription for pro-inflammatory proteins]

Question 4

Structural ingredients and indications for sulfasalazine

Answer 4

Sulfapyridine + 5-ASA

Active cases and maintenance of remission for mild-to-moderate UC

Question 5

Structural ingredients and indications for Mesalamine

Answer 5

Single 5-ASA

Active cases and maintenance of remission for mild-to-moderate UC

Question 6

Structural ingredients and indications for Olsalazine

Answer 6

2 molecules of 5-ASA

Maintenance of remission of mild-to-moderate UC

Question 7

Structural ingredients and indications for Balsalazide

Answer 7

Inert carrier + 5-ASA

Active cases of mild-to-moderate UC

Question 8

Side effects of 5-ASA agents

Answer 8

Dizziness, headache, fatigue

Epigastric distress (anorexia, abdominal pain, N/V/D)

There are fewer systemic SEs with pure 5-ASA products (non-sulfasalazine) and topical formulations

Question 9

Contraindications to 5-ASA agents

Answer 9

All 5-ASA compounds are contraindicated in ASA-allergic patients

Sulfasalazine is contraindicated in sulfonamide-allergic patients

Question 10

MOA of TNF-alpha inhibitors

Answer 10

Binds to and neutralizes membrane-associated and soluble human TNF-alpha mediated pro-inflammatory cell signaling, ultimately blocking leukocyte migration to site of inflammation

Question 11

TNF-alpha inhibitors used for IBD

Answer 11

Adalimumab
Infliximab
Golimumab
Certolizumab

Question 12

Unique feature of certolizumab

Answer 12

Does not contain a fragment crystallizable (Fc) region, thus does not fix complement or cause Ab-dependent cell-mediated cytotoxicity

Question 13

Side effects of TNF-a inhibitors

Answer 13

Infections [must test for TB prior to initiating therapy, since latent infection could be reactivated]

Liver toxicity (increased ALT and AST)

Headache, arthralgias, fatigue

Rare but severe side effects include dermatologic (EM, SJS, TEN) or various malignancies

Question 14

Indications for adalimumab

Answer 14

Active cases and maintenance of remission for moderate-to-severe UC and CD

[maintenance dose administered SQ every 2 weeks]

Question 15

Indications for Infliximab

Answer 15

Active cases and maintenance of remission for moderate-to-severe UC and CD

[maintenance dose administered IV every 8 weeks]

Question 16

Indications for Golimumab

Answer 16

Active cases and maintenance of remission for moderate-to-severe UC

[Maintenance dose administered SQ every 4 weeks]

Question 17

Indications for Certolizumab

Answer 17

Active cases and maintenance of remission for moderate-to-severe CD

[maintenance dose administered SQ every 4 weeks]

Question 18

T/F: All TNF-alpha inhibitors are used in cases of IBD after inadequate response to conventional or immunosuppressant therapy

Answer 18

True

Question 19

MOA of alpha-4 integrin inhibitors

Answer 19

Limits integrin’s associated cell adhesion and subsequent transendothelial migration of leukocytes to site of inflammation

Question 20

Alpha-4 integrin inhibitors used for IBD

Answer 20

Natalizumab (recombinant humanized IgG4k monoclonal Ab)

Vedolizumab (humanized IgG1 monoclonal Ab)

Question 21

Side effects of alpha-4 integrin inhibitors

Answer 21

Infections [Natalizumab associated with Progressive Multifocal Leukoencephalopathy d/t JCV]

Infusion reactions

Anti-medication antibodies (decrease efficacy)

Rare SE of Vedolizumab is increased risk of malignancy

Question 22

Natalizumab is associated with risk of developing Progressive Multifocal Leukoencephalopathy d/t JCV. What are 3 risk factors for developing PML during course of tx?

Answer 22

Treatment >2 years

Prior immunosuppressant tx

Anti-JC virus antibodies

Question 23

Indications for Natalizumab

Answer 23

Active cases and maintenance of remission of moderate-to-severe CD

[note that it is not recommended in combination with immunosuppressants, including TNF-alpha agents]

—maintenance dose administered IV every 4 weeks

Question 24

Indications for Vedolizumab

Answer 24

Active cases and maintenance of remission of moderate-to-severe UC and CD

—maintenance dose administered IV every 8 weeks

Question 25

T/F: all alpha-4 integrin inhibitors are used for IBD after inadequate response to conventional or TNF-alpha therapy

Answer 25

True

Question 26

MOA of IL-12/23 inhibitors

Answer 26

Bind to P40-subunit of IL-12 and IL-23, blocking activation and differentiation of naive T cells and activation of NK cells —> inhibits production of pro-inflammatory cytokines

Question 27

IL-12/23 inhibitor indicated for IBD

Answer 27

Ustekinumab (fully human IgG1k monoclonal Ab)

Question 28

SEs associated with IL-12/23 inhibitors

Answer 28

Infections [must get TB test prior to therapy initiation] Infusion/injection-related allergic reactions Headache, arthralgias, fatigue Rare SE is increased risk of malignancy

Question 29

Indications for IL-12/23 inhibitor

Answer 29

Active cases and maintenance of remission for moderate-to-severe CD [for patients intolerant or inadequate response/resistance to conventional, immune modulators, steroids, or TNF-a therapy] —administered IV as single infusion for induction, then SQ every 8 weeks for maintenance

Question 30

MOA of JAK inhibitors used for IBD

Answer 30

Bind to and inhibit free-floating and bound JAK-1 and JAK-3 (lesser extent JAK-2) Ultimately inhibit gene transcription and more cytokine release

Question 31

JAK-inhibitor indicated for IBD use

Answer 31

Tofacitinib (oral JAK-1/-3 inhibitor)

Question 32

SE’s of Tofacitinib (JAK inhibitor)

Answer 32

Lymphopenia/lymphocytosis Neutropenia/anemia Fatigue Increases in LDL and HDL (minimal ratio change) Rare SE is increased risk of malignancies/serious infections

Question 33

Indications for JAK-inhibitors use in IBD

Answer 33

Active cases and maintenance of remission for moderate-to-severe UC [concomitant use of biologic therapies or potent immunosuppressants not recommended] —administered PO BID

Question 34

Indications for using steroid agents for IBD

Answer 34

Acute and/or SEVERE UC and CD that is uncontrolled by other conventional medications — not used for maintenance of remission unless absolutely required Must use the lowest dose for shortest duration possible