Ixekizumab

Introduction to Ixekizumab

Ixekizumab is a humanized monoclonal antibody that selectively binds and neutralizes interleukin 17A (IL-17A). It belongs to the class of biologic drugs known as IL-17 inhibitors. Ixekizumab was developed for the treatment of autoimmune and inflammatory conditions, primarily plaque psoriasis and psoriatic arthritis.

The drug was approved by the U.S. Food and Drug Administration (FDA) in 2016 under the brand name Taltz® for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Its approved indications have since expanded to include psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.

Mechanism of Action

Ixekizumab exerts its therapeutic effects through the following mechanisms:

  1. IL-17A Neutralization: Ixekizumab selectively binds to and neutralizes IL-17A, a pro-inflammatory cytokine involved in normal inflammatory and immune responses. IL-17A is found in high concentrations in psoriatic plaques.
  2. Inhibition of Inflammatory Cascade: By neutralizing IL-17A, ixekizumab inhibits the inflammatory cascade, including the release of pro-inflammatory cytokines, chemokines, and mediators of tissue damage.
  3. Reduction of Epidermal Hyperplasia: In psoriasis, ixekizumab helps reduce epidermal hyperplasia and keratinocyte proliferation, leading to normalization of skin architecture.
  4. Modulation of Neutrophil Migration: Ixekizumab indirectly reduces neutrophil migration to inflammatory sites by inhibiting IL-17A-induced chemokine production.
  5. Suppression of Th17 Cell Function: By targeting IL-17A, ixekizumab may also indirectly suppress the function of Th17 cells, which are key players in psoriasis and other autoimmune conditions.

Indications

Ixekizumab is approved for the following indications in adults:

  • Moderate-to-Severe Plaque Psoriasis: In patients who are candidates for systemic therapy or phototherapy.
  • Active Psoriatic Arthritis
  • Active Ankylosing Spondylitis
  • Active Non-radiographic Axial Spondyloarthritis with objective signs of inflammation

Pediatric Indications:

  • Moderate-to-Severe Plaque Psoriasis: In patients 6 years and older who are candidates for systemic therapy or phototherapy.

Dosage and Administration

For adult patients:

  • Plaque Psoriasis:
    • 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
  • Psoriatic Arthritis:
    • For patients with coexistent moderate-to-severe plaque psoriasis: Use the dosing regimen for plaque psoriasis.
    • For other patients: 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.
  • Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis:
    • 160 mg (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.

For pediatric patients (6 years and older with plaque psoriasis):

  • Weight ≥ 50 kg: Same as adult dosing.
  • Weight 25-50 kg:
    • 80 mg at Week 0, followed by 40 mg at Weeks 2, 4, 6, 8, 10, and 12, then 40 mg every 4 weeks.
  • Weight < 25 kg:
    • 40 mg at Week 0, followed by 20 mg at Weeks 2, 4, 6, 8, 10, and 12, then 20 mg every 4 weeks.

Adverse Effects

Common adverse reactions (incidence ≥ 1%) associated with ixekizumab include:

  • Injection site reactions
  • Upper respiratory tract infections
  • Nausea
  • Tinea infections
  • Mucocutaneous candidiasis
  • Influenza
  • Rhinitis
  • Conjunctivitis
  • Inflammatory bowel disease
  • Decreased neutrophil count

Serious adverse effects:

  • Infections: Ixekizumab may increase the risk of infection. Consider the risks and benefits prior to initiating treatment in patients with chronic or active infections.
  • Inflammatory Bowel Disease: Cases of new or exacerbations of pre-existing inflammatory bowel disease have been reported.
  • Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported with ixekizumab.

Precautions and Contraindications

Contraindications:

  • Serious hypersensitivity reaction to ixekizumab or to any of the excipients

Precautions:

  1. Infections: Ixekizumab may increase the risk of infection. Exercise caution when considering ixekizumab for patients with chronic or recurrent infections. Patients should be evaluated for tuberculosis (TB) infection prior to initiating treatment.
  2. Inflammatory Bowel Disease: Monitor patients for onset or exacerbation of inflammatory bowel disease. Discontinue treatment if IBD develops or exacerbates.
  3. Hypersensitivity Reactions: If a serious allergic reaction occurs, discontinue ixekizumab immediately and initiate appropriate therapy.
  4. Immunizations: Prior to initiating therapy with ixekizumab, consider completion of all age-appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with ixekizumab.
  5. Pregnancy: Limited data available on use in pregnant women. As a precautionary measure, it's preferable to avoid the use of ixekizumab during pregnancy.
  6. Breastfeeding: No data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for ixekizumab.
  7. Pediatric Use: Safety and efficacy have been established in pediatric patients aged 6 years and older with moderate-to-severe plaque psoriasis. Safety and efficacy in pediatric patients below the age of 6 have not been established.
  8. Geriatric Use: Of the 4204 psoriasis subjects exposed to ixekizumab in clinical trials, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.


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