Lecture 9 IBD Part 3 Flashcards
Regarding treatments for IBD (MTX, SSZ, AZA, CsA) what lab values should be monitored and how often?
Timeline: MTX, SSZ, CsA should be monitored baseline and every 1-3 months
AZA monitored at baseline and every 2-4 weeks,,, CBC/diff: all 4
ALT: all 4,, Albumin: all 4
SCr: all except AZA
CXR: only at baseline for MTX
HBV/HCV: only at baseline for MTX and SSZ
What are different tumor necrosis factor (TNF-alpha) inhibitors and their doses and their indications?
Adalimumab (fully humanized MAB)- 160 mg x 1 then 80 mg at 2 weeks, then 40 mg SC every other week ⇒ used for CD and UC
Certolizumab (pegylated Fab fragment of fully humanized MAB)- 400 mg SC at 0, 2, and 4 weeks, then 400 mg every 4 weeks ⇒ for UC
Golimumab (fully humanized MAB)- 200 mg x 2 then 100 mg at 2 weeks, then 50 mg (up to 100 mg) SC every 30 days ⇒ for UC
Infliximab (chimeric mouse/human MAB)- 5 mg/kg IV at 0, 2, and 6 weeks, then 8 weeks (can be upped to 10 mg/kg and/or 6 weeks) OR 120 mg SC every 2 weeks ⇒ used for CD and UC
What is the onset of TNF-alpha inhibitors and their indications in IBD?
Onset: 2-4 weeks, assess in 8-12 weeks for sx response
Indications: use +/- with MTX or AZA
used in moderate-severe UC and CD who haven’t responded to other tx, very effective healing rates for fistulas, responders may continue tx long term (may need dose increase), some pt may be successfully maintained on immunomodulatory tx alone after achieving remission with these (step-down tx)
What are hypersensitivity rxn that can specifically happen with infliximab?
Acute Infusion Reaction (INFL): occurs within 24 hours of infusion, most common within 10 minutes-4 hours
can premedicate - loratadine/cetirizine + acetaminophen +/- IV steroid
most mild - 5-10%: pain, itching at infusion site, fever, chills, flushing, hold infusion and restart at slower rate
severe rxn <1%: hypotension, chest pain, dyspnea, discontinue infusion
Delayed Hypersensitivity Reaction (INFL): antibodies to the murine portion form, serum sickness like rxn - fever, hives, malaise, joint pain, myalgia, pruritis, H/A
seen around 1 week (1-14 days) after repeated infliximab infusion
Tx with antihistamine, acetaminophen x 3 days (steroids prn), avoid further use of this
What are AEs that specifically happen with adalimumab and golimumab with infusion?
occurs within 1-2 days of injection - most common with 2nd/3rd injection then disappears
most mild 5-10% - red, itchy, painful (size up to loonie)
Tx with loratadine/cetirizine, and montelukast if long lasting
What are AEs associated with TNFi tx and contraindications for its use in IBD?
AE: Common - URTI (30%): more common in first year, comorbidities like DM, COPD, and steroid use increase risk
H/A (10-25%)
nausea, upset stomach, diarrhea (10-15%)
back pain, muscle ache (<10%)
Uncommon - non-melanoma skin cancer, psoriasis, lupus/lupus-like syndrome
Rare - reactivation of infections (TB, herpes, hepatitis), serious infections may progress faster with signs masked
Contra: current infection (bacterial, viral, fungal), moderate-severe HF, hx of MS, live attenuated vaccines (ex. mumps, measles, rubella, etc), use with other biologic or targeted tx
Use with Caution: FHx of MS, lymphomas, skin cancer
What is anti-integrin tx vedolizumab (Entyvio) for IBD (Drugs, MOA, dose, efficacy/indication, AE)?
MOA: binds alpha4beta7-integrin on pathogenic gut-homing memory T lymphocytes, selectively inhibiting adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1)
Dose: 300 mg IV over 30 min at 0, 2, and 6 weeks, then 300 mg IV every 8 weeks
Efficacy: can be used +/- MTX or AZA - assess for sx at 8-14 weeks in UC and 10-14 in CD
Indication: moderate-severe UC or CD with loss of response or inadequate response or intolerant to TNFi - studied in combo with AZA, 6-MP, MTX, aminosalicylates, and steroids
AE: URTI: more common in first year, comorbidities like DM, COPD, and steroid use increase risk
H/A
nausea, upset stomach, diarrhea
back pain, muscle ache, may increase liver enzymes, bilirubin
Ustekinumab (Stelara, biosimilars) for IBD tx (MOA, dose, efficacy, indication, AE, Contra)
MOA: antagonist to the shared p40 subunit of IL-12 and IL-23
Dose: induction - 260-520 mg IV infusion over 1 hour
maintenance - 90 mg SC every 8 weeks (some every 12 weeks)
Efficacy: used +/- MTX or AZA - assess for sx in 6-10 weeks
Indication: moderate-severe CD and UC with loss of response or inadequate response or intolerant to conventional therapy and TNFi
AE: URTI: more common in first year, comorbidities like DM, COPD, and steroid use increase risk
H/A
nausea, upset stomach, diarrhea,, back pain, muscle ache
Contra: current infection, live vaccines, other biologic/targeted tx
Mirikizumab (Omvoh) for IBD tx (MOA, dose, indication, AE, contra)
MOA: antagonist that binds to the p19 subunit of IL-23
Dose: induction - 300 mg IV over >30 min at 0, 4, and 8 weeks, assess for response at 12 weeks
maintenance - 200 mg (2 x 100 mg) SC every 4 weeks
Indication: used +/- MTX or AZA
moderate-severe UC with loss of response or inadequate response or intolerant to conventional tx, a biologic, or JAKi
AE: URTI: more common in first year, comorbidities like DM, COPD, and steroid use increase risk
H/A
nausea, upset stomach, diarrhea
back pain, muscle ache
Contra: current infection, live vaccines, other biologic-targeted tx
Risankizumab (Skyrizi) for IBD tx (MOA, dose, indication, AE, contra)
MOA: selective antagonist to p19 subunit of IL-23
Dose: induction - 600 mg IV at 0, 4, and 8 weeks then 360 mg SC at 12 weeks,, maintenance - 360 mg SC every 8 weeks
Indication: used +/- MTX or AZA
moderate-severe CD with loss of response or inadequate response or intolerant to conventional therapy, a biologic, and/or steroid dependence (NOT COVERED BY ABC)
AE: URTI: more common in first year, comorbidities like DM, COPD, and steroid use increase risk
H/A,, nausea, upset stomach, diarrhea,, back pain, muscle ache, may cause liver enzyme elevation
Janus kinase inhibitors (JAKi) for IBD tx (MOA, Drugs and their indications, dose)
MOA: small molecule inhibitors of this induced pro-inflammatory cytokine production
Drugs+indication+dose: Tofacitinib (Xeljanz) - indicated for moderate-severe UC, both induction tx and maintenance of remission (d/c if no response by 16 weeks)
induction - 10 mg PO BID for >/= 8 weeks
maintenance - 5 mg BID (up to 10 mg BID)
Upadacitinib (Rinvoq) - indicated for moderate-severe UC and CD, both induction tx and maintenance of remission (d/c if not responding),, induction - 45 mg PO QD x 8 weeks (UC)/ x 12 weeks (CD)
maintenance - 15 mg QD (up to 30 mg QD if < 65)
What are AEs and cautions for JAKi in IBD tx?
AE: Common (>5%) - URTI, nasopharyngitis, H/A, diarrhea (TOF)
Less Common - serious infections (including opportunistic, TB, herpes zoster), neutropenia, decreased Hb, increased LDL (0.6 mmol/L), ALT/AST elevation (>1x ULN), bradycardia (with TOF, decrease 5-7 bpm, lengthen PR interval)
Caution: VTE - signal with baricitinib (watch for all of them), CV events/cancers (post-marketing), contra in pregnancy/lactation - d/c 6 weeks prior
TOF and UPA are metabolized by CYP3A4 so important to avoid with strong inhibitors/inducers
How should JAKi be monitored, what lab values, and time frames?
CBC/diff: measured at baseline, at 4-8 weeks, and every 3 months
Lipids: at baseline, at 4-8 weeks, every 6 months with TOF, and periodically with UPA
ALT/AST: at baseline, at 4-8 weeks, every 3 months
Vitals (HR): for TOF only - at baseline, and periodically
