Ixekizumab

Usage

Ixekizumab is prescribed for the treatment of:

• Moderate to severe plaque psoriasis: In patients 6 years and older who are candidates for systemic therapy or phototherapy.
• Active psoriatic arthritis: In adults.
• Active ankylosing spondylitis: In adults.
• Active non-radiographic axial spondyloarthritis: In adults with objective signs of inflammation.

Pharmacological Classification: Interleukin-17A (IL-17A) antagonist, a biologic medication classified as an immunomodulator.

Mechanism of Action: Ixekizumab works by selectively binding to and neutralizing IL-17A, a cytokine that plays a key role in the inflammatory processes associated with these conditions. By inhibiting IL-17A, ixekizumab reduces inflammation and its associated symptoms.

Alternate Names

International Nonproprietary Name (INN): Ixekizumab

Brand Name: Taltz

How It Works

Pharmacodynamics: Ixekizumab binds specifically to IL-17A, preventing it from interacting with its receptor. This inhibits the downstream pro-inflammatory effects driven by IL-17A, including the production of other cytokines, chemokines, and mediators involved in inflammation and joint damage.

Pharmacokinetics:

• Absorption: Following subcutaneous administration, ixekizumab reaches peak serum concentrations in approximately 5 days. Steady-state is achieved by Week 5 (range 2–10 weeks) with the standard dosing regimen for plaque psoriasis.
• Metabolism: The metabolism of ixekizumab is not fully characterized. It is presumed to follow the typical degradation pathways for IgG antibodies, which involves catabolism into small peptides and amino acids.
• Elimination: Ixekizumab has a half-life of approximately 13 days. Elimination primarily occurs through catabolism.

Mode of Action: Ixekizumab works by inhibiting the IL-17A signaling pathway. It directly neutralizes free IL-17A, preventing the cytokine from activating IL-17 receptors. This, in turn, reduces the expression of various inflammatory mediators, ultimately leading to decreased inflammation.

Receptor Binding: Ixekizumab selectively targets IL-17A, a pro-inflammatory cytokine.

Elimination Pathways: Primarily through IgG catabolism (proteolytic degradation to small peptides and amino acids), rather than specific hepatic or renal pathways.

Dosage

Standard Dosage

Adults:

• 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, Ankylosing Spondylitis: 160 mg (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.
• Non-Radiographic Axial Spondyloarthritis: 80 mg every 4 weeks.

Children (Plaque Psoriasis, 6 years and older):

• > 50 kg: 160 mg (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.
• 25-50 kg: 80 mg at Week 0, followed by 40 mg every 4 weeks.
• < 25 kg: 40 mg at Week 0, followed by 20 mg every 4 weeks. Doses of 20 mg and 40 mg should be prepared and administered by a qualified healthcare professional.

Special Cases:

• Elderly Patients: No dose adjustment is required.
• Patients with Renal Impairment: No dose adjustment recommendations are available due to limited studies.
• Patients with Hepatic Dysfunction: No dose adjustment recommendations are available due to limited studies.

Clinical Use Cases

Ixekizumab is not indicated for:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations

It is specifically for chronic inflammatory conditions.

Side Effects

Common Side Effects:

• Upper respiratory tract infections (nasopharyngitis, sinusitis)
• Injection site reactions (erythema, pain, pruritus)
• Nausea
• Diarrhea

Rare but Serious Side Effects:

• Inflammatory bowel disease (new or worsening)
• Serious infections (e.g., tuberculosis)
• Hypersensitivity reactions (e.g., angioedema, anaphylaxis)

Adverse Drug Reactions (ADR):

• Severe hypersensitivity reactions

Contraindications:

• Hypersensitivity to ixekizumab or any of its components
• Active tuberculosis or other serious infections

Drug Interactions:

• Live vaccines should be avoided during ixekizumab treatment.
• While interactions with CYP450 substrates have not been shown to be clinically significant, monitoring may be considered when initiating or discontinuing ixekizumab in patients taking drugs with a narrow therapeutic index that are metabolized by CYP enzymes (e.g., warfarin).

Pregnancy and Breastfeeding:

• Pregnancy: There is limited data on the use of ixekizumab during pregnancy. Ixekizumab may cross the placenta. It is generally recommended to avoid use during pregnancy unless the potential benefit outweighs the potential risk.
• Breastfeeding: It is unknown whether ixekizumab is present in human milk. Given the potential for adverse effects in the infant, a decision should be made whether to discontinue breastfeeding or discontinue the drug.

Drug Profile Summary

• Mechanism of Action: Neutralizes interleukin-17A, reducing inflammation.
• Side Effects: Upper respiratory infections, injection site reactions, nausea, diarrhea. Rarely, inflammatory bowel disease or serious infections.
• Contraindications: Hypersensitivity, active tuberculosis.
• Drug Interactions: Avoid live vaccines. Monitor patients on narrow therapeutic index drugs metabolized by CYP enzymes.
• Pregnancy & Breastfeeding: Limited data. Generally avoid use.
• Dosage: Refer to the dosage section above.
• Monitoring Parameters: Monitor for signs and symptoms of infection, inflammatory bowel disease, and hypersensitivity reactions. Periodically evaluate response to treatment.

Popular Combinations

Ixekizumab can be used with conventional DMARDs (e.g., methotrexate) in the treatment of psoriatic arthritis.

Precautions

• Screen patients for latent tuberculosis before initiating therapy.
• Complete age-appropriate immunizations prior to treatment.
• Monitor for signs and symptoms of infection.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ixekizumab?

A: See the detailed dosage section above.

Q2: What are the common side effects of Ixekizumab?

A: The most common side effects include upper respiratory tract infections, injection site reactions, nausea, and diarrhea.

Q3: How is Ixekizumab administered?

A: Ixekizumab is administered by subcutaneous injection. Patients may self-inject after appropriate training.

Q4: Can Ixekizumab be used during pregnancy?

A: Ixekizumab should be avoided during pregnancy unless the potential benefit outweighs the risk. Discuss with a healthcare professional.

Q5: Is Ixekizumab safe for breastfeeding mothers?

A: The safety of ixekizumab during breastfeeding is unknown. A decision should be made whether to discontinue breastfeeding or discontinue the drug.

Q6: What should be done before starting Ixekizumab treatment?

A: Patients should be screened for latent tuberculosis infection and have all age-appropriate vaccinations.

Q7: How does Ixekizumab work at the cellular level?

A: Ixekizumab binds to and neutralizes IL-17A, preventing it from interacting with its receptor and triggering the inflammatory cascade.

Q8: What are the potential long-term effects of Ixekizumab?

A: Long-term safety data is still being collected, but vigilance is advised for potential long-term effects, including the possibility of increased risk of certain infections.

Q9: Can Ixekizumab be used in patients with renal or hepatic impairment?

A: Ixekizumab has not been extensively studied in patients with renal or hepatic impairment. No specific dosage adjustments are recommended, but caution should be exercised.

Q10: When should Ixekizumab treatment be discontinued?

A: Treatment discontinuation should be considered if a patient shows no response after 16-20 weeks.