IBD II

Question 1

TDM of Biologics

potential for determining concentrations of ___ and ___
- most data with infliximab and adalimumab
- consider if ___ of treatment response (reactive TDM) - role of proactive TDM unclear
- check ___ concurrently
- assay methodology may be important
- economic value unclear
* may help justify dose increases to insurer

Answer 1

• drugs, ADAs
• lose
• ADA

Question 2

TDM of Biologics

optimal trough concentrations not clear – ___ ___

Answer 2

moving target

Question 3

know how to use this chart:
- sub- thera drug levels + ADAs = ____
- sub-thera drug levels, no ADAs = ___
- thera drug levels +ADAs = ___
- thera drug levels, no ADAs = ___

Answer 3

• change to alternate drug wthin the same calss
• dose escalate
• repeat TDM, switch to out of class biologic agent
• switch to out of class biologic agent

Question 4

Clinical Controversy: “Biosimilars”

• biological product that is
  approved based on a showing
  that it is highly ___ to an
  already-approved biological
  product
• must show it has no clinically
  meaningful differences in terms
  of ___ and ___
• do not switch to corresponding
  biosimilar if loss of ___ to
  the brand

Answer 4

• similar
• safety, effectiveness
• response

Question 5

Tofacitinib (Xeljanz)

oral ___ inhibitor
- family of enzymes involved in immune signaling
- approved for ___ only for pts who have had an inadequate response or who are intolerant to ___ blockers

• 10 mg bid or 22 mg XR daily for 8 weeks (up to 16)
• then 5 or 10 mg bid or 11 or 23 mg XR daily
• D/C after ___ weeks of 10 mg bid or 22 mg XR daily if response not adequate
• use lowest effective dose to maintain response

Answer 5

• JAK
• UC
• TNF
• 16

Question 6

Tofacitinib (Xeljanz)

• relatively ___ onset
• option for patients who fail ___
• should NOT be used with ___
  (e.g., AZA, CYA, etc.) or ___
• relatively ___ half live (3 h)
• eliminated via ___ metabolism (~70%) (CYP3A and CYP2C19) and renal excretion (~30%)

moderate/severe renal impairment or moderate hepatic impairment:
- decrease daily dosage by 50%
- avoid in severe hepatic impairment

Answer 6

• rapid
• biologics
• immunosuppressants, biologics
• short
• hepatic

Question 7

Tofacitinib (Xeljanz) - Drug Interactions

strong CYP3A ___ (e.g., ketoconazole) or moderate CYP3A inhibitor with a strong ___ inhibitor (e.g., fluconazole )
* decrease daily dosage by 50%

strong CYP3A ___ (e.g., rifampin)
* avoid use

Answer 7

• inhibitor
• CYP2C19
• inducer

Question 8

Tofacitinib (Xeljanz) - ADRs

common:
- diarrhea, elevated ___ , headache, ___ , increased creatine phosphokinase,
nasopharyngitis, rash, URI

rare
* malignancy ( ___ and other)
* serious infection (including activation of latent ___ )
* neutropenia (see PI for recommendations)
* hypersensitivity
– angioedema and urticaria

Answer 8

• cholesterol
• shingles
• lymphoma
• TB

Question 9

Tofacitinib (Xeljanz) - ADRs

black-box warning:
- increase ___ in RA patients 50 years and older with at least one CV risk factor
- ___ (PE, DVT, arterial) = increased risk in RA patients 50 years and older with at least one CV risk factor

FDA Drug Safety Communication (DSC) (02/2021)
- review of surveillance trial including 4,362 RA patients with at least 1 CV risk factor receiving either tofacitinib 5 mg
bid, 10 mg bid, or a TNF blocker
- increased risk of death, serious CV events, blood clots, and malignancies (lymphomas, lung cancer [esp. in
current/past smokers) with both doses of tofacitinib

Answer 9

• mortality
• thrombosis

Question 10

Tofacitinib (Xeljanz) - ADRs

increased risk of serious infections (bacterial, viral, fungal)
- avoid if active infection
- tuberculin test ( ___ ), ___ , Hepatitis B/C prior to therapy
- ensure vaccinations up to date
- live vaccines contraindicated during tx and for __ mo after

Answer 10

• PPD, CXR
• 3

Question 11

Tofacitinib (Xeljanz) - monitoring

• CXR, ___
• Hep B, C
• ___ - q 3 months
• ___ - q 1-2 months then q 3 months
• ___ - 1-2 months after start, then periodically
• ___ - 1-2 months after start, then periodically
• infection - monitor for s/s
• ___ exam - periodically

Answer 11

• PPD
• ANC
• CBC
• lipids
• LFTs
• skin

Question 12

Upadacitinib (Rinvoq)

oral selective ___ inhibitor
- family of enzymes involved in immune signaling
- approved for ___ and ___
- who have had an inadequate response to or who are intolerant to ___ blockers

Answer 12

• JAK
• UC, CD
• TNF

Question 13

Upadacitinib (Rinvoq)

UC
- 45 mg daily for __ weeks then 15 mg daily
- can use 30 mg daily for refractory, severe, extensive disease
- D/C if response not adequate with ___ mg daily
- use lowest effective dose to maintain response

CD
- 45 mg daily for __ weeks then 15 mg daily
- can use 30 mg daily for refractory, severe, extensive disease
- D/C if response not adequate with ___ mg daily
- use lowest effective dose to maintain response

Answer 13

• 8, 30
• 16, 30

Question 14

Upadacitinib (Rinvoq)

• relatively ___ onset
• option for patients who fail ___
• should NOT be used with ___
  (e.g., AZA, CYA, etc.) or ___
• relatively ___ half live (4 h)
• eliminated via ___ metabolism (~35% esp.CYP3A), renal excretion (~25%), unchanged in feces (~38%)
• dose adjustments required in renal impairment and mild-moderate hepatic impairment
• not recommended in end stage renal disease or severe hepatic impairment

Answer 14

• rapid
• biologics
• immunosuppressants, biologics
• short
• hepatic

Question 15

Upadacitinib (Rinvoq) - Drug interactions

strong CYP3A ___
- 30 mg daily for ___, 15 mg daily for ___

strong CYP3A ___
- avoid use

Answer 15

• inhibitor
• induction, maintenance
• inducer

Question 16

Upadacitinib (Rinvoq) - ADRs

black-box warnings similar to ___
- unclear if same safety concerns extend to upadacitinib

risk of serious ___ (bacterial, viral, fungal)
- avoid if active infection
- tuberculin test ( ___ ), CXR, Hepatitis B/C prior to therapy
- ensure vaccinations up to date
- live vaccines contraindicated immediately ___ to and during therapy

Answer 16

• tofacitinib
• infections
• PPD
• prior

Question 17

Upadacitinib (Rinvoq) - ADRs

common:
- upper respiratory tract infection, ___ , increased creatine phosphokinase, elevated ___ , headache, ___

Answer 17

• acne
• lipids
• shingles

Question 18

Upadacitinib (Rinvoq) - ADRs

rare:
- malignancy ( ___ and other)
- serious infection (including activation of latent ___ )
- increases in ___
- anemia
- neutropenia (see PI)
- lymphopenia (see PI)

Answer 18

• lymphoma
• TB
• LFTs

Question 19

Upadacitinib (Rinvoq) - ADRs

rare
- hypersensitivity - angioedema and urticaria

potentially ___ , excreted in breast milk
- avoid in ___ and ___

Answer 19

• teratogenic
• pregnancy, lactation

Question 20

Upadacitinib (Rinvoq) - monitoring

• ___ , ___
• Hep B, C
• ___ / ___ - q 3 months
• ___ - q 1-2 months then q 3 months
• ___ - 12 weeks after start, then periodically
• ___ - 1-2 months after start, then periodically
• ___ - monitor for s/s
• ___ - exam periodically

Answer 20

• CXR, PPD
• ANC/ALC
• CBC
• lipids
• LFTs
• infection
• skin

Question 21

Ozanimod (Zeposia)

oral selective ___ receptor modulator
- prevents ___ mobilization to inflammatory sites

approved for ___ only
- moderate – severe active UC
- 7 day dose titration: 0.23 mg daily days 1-4, 0.46 mg daily days 5-7, 0.92 mg daily day 8 and after
- if a dose is missed in the first __ weeks of treatment, ___ titration regimen

should not be used with non-corticosteroid ___ or immune-modulating drugs

Answer 21

• S1P
• lymphocyte
• UC
• 2, reinitiate
• immunosuppressive

Question 22

Ozanimod (Zeposia)

contraindicated in patients who in last 6 months experienced:
- ___ , unstable angina, ___, TIA, decompensated heart failure
requiring hospitalization, Class III or IV heart failure
- with Mobitz type II 2 nd or 3rd degree AV block, sick sinus syndrome, or SA block unless patient has functioning
pacemaker
- with severe untreated ___ ___
- taking a ___ inhibito r- active metabolite of ozanimod is an ___ inhibitor
- half life ~ __ hours

metabolized by ALDH/ADH and CYP3A4
- active metabolites metabolized by CYP2C8
- not recommended for use in ___ impairment

Answer 22

• MI, stroke
• sleep apnea
• MAO, MAO-B
• 21

Question 23

Ozanimod (Zeposia) - ADRs

potential increased risk of infections
* potential risk of ___ (reported in patients treated with
S1P receptor modulators)
* recommended to vaccinate against ___ prior to
treatment if unvaccinated/not previously infected
* live-attenuated vaccines contraindicated (within __
month of start, during, or __ months after stopping)

___ /AV conduction delays
* consult with cardiologist if any underlying ___ ,
CV disease

Answer 23

• infections
• PML
• varicella
• 1, 3
• bradycardia, arrhythmias

Question 24

Ozanimod (Zeposia) - ADRs

___ injury/elevated transaminases
* ~1-1.6% of patients with elevations of ALT to 5-fold
upper limit of normal, ~2.6-5.5% with elevations up to 3-fold upper limit of normal
* not recommended in patients with LFTs > __ -fold upper
limit of normal

moderate increase in ___ (~5 mm Hg)
* ___ crisis has been reported

• ___ effects are dose dependent reductions in FEV1
• ___ edema
• reversible posterior leukeoencephalopathy syndrome
  ( ___ )/posterior reversible encephalopathy syndrome ( ___ )) (case report)

Answer 24

• liver
• 5
• SBP
• hypertensive
• respiratory
• macular
• RPLS, PRES

Question 25

# Ozanimod (Zeposia) - Drug interactions ___ and ___ drugs * potential ___ crisis (active metabolite inhibits ___ ) combination ___ and ___ * potential additive effects on heart rate (not studied) foods high in ___ - ___ inhibitors = contraindication (active metabolite inhibits ___ ) strong CYP2C8 inhibitors = ___ exposure of active metabolites, co-administration not recommended strong CYP2C8 inducers = ___ exposure of active metabolites (possible reduced efficacy), co-administration should be avoided

Answer 25

- adrenergic, serotonergic - hypertensive, MAO-B - BB, CCB - tyramine - MAO, MAO-B - increases - decreases

Question 26

# Ozanimod (Zeposia) - monitoring ****“treat it like a ___ ” - ___ , ___ - Hep B, C - CBC - periodically - ___ - periodically - infection - monitor for s/s (for 3 months after d/c) - ___ - each visit - spirometry - if clinically indicated - ___ - ___ - regular exams

Answer 26

biologic - CXR, PPD - LFTs - BP - ECG - optho

Question 27

# Estrasimod (Velsipity) oral selective ___ receptor modulator - interacts with S1P receptors on ___ - prevents lymphocyte ___ to inflammatory sites approved for ___ only - moderate – severe active UC - 2 mg daily should not be used with non-corticosteroid ___ or immune-modulating drugs

Answer 27

- S1P, lymphocytes - mobilization - UC - immunosuppressive

Question 28

# Estrasimod (Velsipity) contraindicated in patients who in last 6 months experienced: - ___ , unstable angina, ___ , TIA, decompensated ___ requiring hospitalization, Class III or IV heart failure - various cardiac ___ abnormalities - half life ~ __ hours metabolized by CYP2C8, CYP2C9, CYP3A4 - interactions possible (see PI) - does not have same warnings regarding ___ inhibitors as oxanimod

Answer 28

- MI, stroke, HF - conduction - 30 - MAO

Question 29

# Estrasimod (Velsipity) - ADR potential increased risk of infections * potential risk of ___ due to __ virus infection * recommended to vaccinate against ___ prior to treatment if unvaccinated/not previously infected * live-attenuated vaccines contraindicated (within __ month of start, during, or __ months after stopping) - ___ / AV conduction delays * consult with cardiologist if any underlying ___ , CV disease

Answer 29

- PML, JC - varicella - 1, 3 - bradycardia - arrhythmias

Question 30

# Estrasimod (Velsipity) - ADRs ___ injury/elevated transaminases * not recommended in patients with severe ___ impairment - moderate increase in ___ - ___ edema - reversible posterior leukeoencephalopathy syndrome ( ___ )/posterior reversible encephalopathy syndrome ( ___ )) (case report) - ___ effects (recall oxanimod is c/o with ___ ___)

Answer 30

- liver - hepatic - SBP - macular - RPLS, PRES - respiratory, sleep apnea

Question 31

# Estrasimod (Velsipity) “treat it like a ___ ” - ___ , ___ - Hep B, C* - CBC - periodically* - ___ - periodically* - ___ - monitor for s/s (for 3 months after d/c) - ___ - each visit* - spirometry if clinically indicated - ___ - ___ regular exams*

Answer 31

biologic - CXR, PPD - LFTs - infection - BP - ECG - optho

Question 32

# Antimicrobials ciprofloxacin, metronidazole, rifamycin antibiotics - can be used as ___ therapy for treatment of complications * may be used in ___ associated with fistulas/abscesses, perianal involvement, post resection little efficacy in treating luminal disease, generally not recommended ADRs * agent specific ADRs * resistance * Clostridium difficile

Answer 32

- adjunctive - CD