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T-Cell Costimulatory Modulator

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T-Cell Costimulatory Modulator, T-Cell Co-Stimulatory Blocker, T-Cell Co-Stimulatory Inhibitor, T Lymphocyte Costimulation Activity Blockade, Costimulatory T-Cell Receptor, Belatacept, Nulojix

  • See Also
  1. Abatacept
  • Indications
  1. Renal Transplant Rejection prophylaxis
    1. Belatacept (Nulojix)
      1. Used in combination with Basiliximab induction, Mycophenolate Mofetil, and Corticosteroids
  2. Rheumatoid Arthritis
    1. Abatacept (Orencia)
  • Contraindications
  1. Non-immune to Epstein-Barr Virus
  2. Liver Transplant (higher risk of graft loss)
  • Mechanism
  1. Costimulatory T-Cell Receptor
    1. T-Cells are stimulated via CD3 with co-stimulation via various agents including CD28, CD80, CD86
    2. Images
      1. BCellActivation.jpg
  2. T-Cell Co-Stimulatory Blockers
    1. CD28 Inhibition
      1. Increases T-Cell Activation threshold and inhibits T-Cell proliferation
      2. Abatacept inhibits CD28 to CD80/CD66 binding
      3. Belatacept is derived from Abatacept, and also binds CD80, CD86
  • Medications
  1. Abatacept (Orencia)
    1. Abatacept is a fusion Protein of the extracellular CTLA4 receptor bound to the IgG Fc fragment
  2. Belatacept (Nulojix)
    1. Belatacept is derived from Abatacept and adapted to also bind CD80, CD86
    2. Available in lyophilized powder for injection, 250 mg per vial
  • Dosing
  • Belatacept (Nulojix)
  1. See other references for specific dosing regimens per indication
  2. Prescribers are typically specialists knowledgeable about the risks and monitoring
  3. Post-Renal Transplant (combined with other agents, e.g. Basiliximab induction, Mycophenolate Mofetil, and Corticosteroids)
    1. Initial Post-Transplant dosing 10 mg/kg IV over 30 minutes on days 1, 5, 14, 28, 56 and 84 (12 weeks)
    2. Maintenance Post-Transplant 5 mg/kg IV over 30 minutes
      1. Start week 16 (following initial dosing to week 12)
      2. Administer every 4 weeks (each dose +/- 3 days)
  • Adverse Effects
  • Belatacept (Nulojix)
  1. See Abatacept
  2. Post-transplant Lymphoproliferative Disorder (PTLD)
    1. Higher risk if non-immune to Epstein-Barr Virus (Antibody negative)
    2. Most commonly involves the Central Nervous System (CNS)
  3. Secondary malignancy
  4. Progressive Multifocal Leukoencephalopathy (PML)
  5. Serious Infections
    1. Includes opportunistic infections; Bacterial, viral, fungal, and Protozoal Infections
    2. Tuberculosis
    3. Polyoma virus-associated nephropathy
    4. Cytomegalovirus (post-transplant prophylaxis recommended)
    5. Pneumocystis (post-transplant prophylaxis recommended)
  6. Other common adverse effects
    1. Cardiovascular
      1. Hypertension
      2. Peripheral Edema
    2. Gastrointestinal
      1. Nausea or Vomiting
      2. Diarrhea or Constipation
    3. Neurologic
      1. Headache
    4. Hematologic
      1. Anemia
      2. Leukopenia
  • Safety
  • Belatacept (Nulojix)
  1. Unknown safety in pregnancy
  2. Avoid in Lactation
  • Drug Interactions
  1. Live Vaccines
    1. Avoid use with Costimulatory T-Cell Receptor Antagonists
  • Resources
  1. Belatacept (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c16ac648-d5d2-9f7d-8637-e2328572754e