IBD Part 2.2 - therapeutic options Flashcards
Biologics
Tumor necrosis factor-alpha (TNF-a) antagonists
Infliximab:
§ chimeric mouse/human monoclonal antibody
anti-TNF-a
Adalimumab:
§ fully humanized monoclonal antibody anti-TNF-a
Golimumab:
§ fully humanized monoclonal antibody anti-TNF-a
Certolizumab:
§ pegylated Fab fragment of fully humanized
monoclonal antibody anti-TNF-a
first 3 have indications for UC and CD
Tumor necrosis factor-alpha (TNF-a) antagonists
Induction therapy?
Maintenance of remission?
Induction therapy:
§ Moderate to severe active CD/UC who have not responded to other therapies
• Note: immunosuppressants are usually continued, may have better effect with immunosuppressants
§ Very effective healing rates of fistulas
Maintenance of remission:
§ In patients who have responded to induction therapy with TNF-a antagonists, shown to help maintain remission
§ Some patients can be successfully maintained on immunosuppressive following induction with TNF-a antagonists.
TNF-a antagonists
Induction: See table 5
Infliximab: UC, CD
• intravenous infusion over 2 hours
• 5mg/kg at weeks 0, 2 and 6 weeks
- Maintenance therapy -> 5mg/kg every 8 weeks
Adalimumab: UC, CD
• Subcutaneous - pre-filled pen, syringe or vial (40mg)
• 160 mg at week 0 and 80 mg at week 2
- Maintenance therapy -> 40 mg every 2 weeks
Golimumab: UC
• Subcutaneous - pre-filled pen, syringe or vial (40mg)
• 200 mg at week 0 and 100 mg at week 2
- Maintenance therapy -> 50 mg every 4 weeks
Certolizumab:
• Subcutaneous – prefilled syringes (200mg)
• 400 mg at week 0, 2 and 4
- Maintenance therapy -> 400 mg every 4 weeks
Adalimumab (Humira)
Administration?
see slide 29, 30
Golimumab (Simponi)
Administration?
see slide 31
Certolizumab (Cimzia)
Administration?
see slide 32
TNF-a Antagonists
Adverse effects:
Acute infusion reaction
§ Occurs within 24 hours of infusion (most common within 10 min to 4 hours)
§ Most are mild: pain/itching at infusion site, fever, chills, flushing, headache (5 - 10% infliximab, 3 – 6% adalimumab, certolizumab)
§ Severe reaction: hypotension, chest pain, dyspnea (<1%)
§ premedicate with diphenhydramine and acetaminophen
TNF-a Antagonists
Adverse effects:
Delayed hypersensitivity reaction with infliximab
§ formation of anti-infliximab antibodies (to murine portion of infliximab)
§ may see delayed infusion reaction in 1 – 2 weeks in patients retreated with infliximab
§ serum sickness like reaction – fever, hives, malaise, joint pain itching
§ avoid use of infliximab if develops delayed hypersensitivity
TNF-a antagonists
Other adverse effects:
§ Increase risk of infection
§ Flushing
§ Increase LFT
§ Loss of response with anti-TNF therapy in some patients over time.
• Now monitoring level anti-TNF therapy– ratio of trough anti-TNF level to anti-TNF antibody level
10-30% of patients
More in infliximab
Anti-TNFa antibodies that are developed
Level of trough and the anti-TNFabody
Make sure there is enoughof trough to be able to have a response
Dosing may be adjusted
TNF-a antagonists
Contraindicated:
Use with caution:
Contraindicated:
§ Patients with significant bacterial
infections
§ Patients with moderate to severe
congestive heart failure (CHF) – New York Heart Association class III or IV
§ Live attenuated vaccines (ie mumps, measles, rubella, etc)
Use with caution: § Reactivation of infections: • Tuberculosis (TB) • Hepatitis B § Preexisting demyelinating disorders (ie MS) § Lymphomas, skin cancer
Anti-integrin therapies
§ Monoclonal antibodies to human integrin
• Vedolizumab (Entyvio R )
§ Indicated for moderate to severe UC or CD with loss of response or inadequate response or intolerant to TNF- a antagonists
IV infusion – 300 mg IV over 30 minutes at 0, 2 and 6 weeks.
Maintenance 300 mg IV every 8 weeks.
Anti-integrin therapies
Adverse effects:
- Hypersensitivity reaction – infusion related
- Headache, nausea, joint pain, fever, fatigue
- Infection – upper respiratory tract, influenzae
- Increase liver function tests
Interleukin antagonist
Ustekinumab (Stelara)
- Antagonist for IL-12 and IL-23
- Indicated for moderate to severe CD with loss of response or inadequate response or intolerant to TNF- a antagonists
- IV infusion over 1 hour and then subcutaneous every 8 weeks
- Adverse effects: hypersensitivity (infusion related), upper respiratory tract infection, headache, tiredness, redness at injection site
Targeted Immunosuppressant
Janice Kinase (JAK) inhibitors
MOA
§ Inhibitors of JAK-induced pro-inflammatory cytokine production
§ Cytokines bind to their receptor, leads to JAK activation and phosphorylation. This activates STAT proteins, which enter the nucleus and regulate gene
transcription (and produces pro-inflammatory cytokines)
• By inhibiting JAK, reduces cytokine production
Targeted Immunosuppressant
Janice Kinase (JAK) inhibitors
Common drug name?
Indication?
Dose?
Adverse effects?
Tofacitinib (Xeljanz)
Indication: moderate to severe UC not responded to other agents
not CD
Both induction therapy and maintenance of remission
Dose: 10 mg po bid x 8 weeks, maintenance 5 – 10 mg bid
Adverse effects:
- Common: decrease WBC (neutrophils, lymphocytes), upper respiratory tract infection, headache, diarrhea, increase LDL, increase LFT (ALT/AST)
- Rare: infections, GI perforation, venous thromboembolism, ?lymphoma/cancer
