Secukinumab

Introduction to Secukinumab

Secukinumab is a fully human monoclonal antibody that selectively targets interleukin-17A (IL-17A). It belongs to the class of biologic drugs known as IL-17 inhibitors. Secukinumab was developed for the treatment of various inflammatory conditions, including psoriasis, psoriatic arthritis, and ankylosing spondylitis.

The drug was approved by the U.S. Food and Drug Administration (FDA) in 2015 under the brand name Cosentyx® for the treatment of moderate to severe plaque psoriasis. Since then, its approved indications have expanded to include psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.

Mechanism of Action

Secukinumab exerts its therapeutic effects through the following mechanisms:

  1. IL-17A Neutralization: Secukinumab selectively binds to and neutralizes IL-17A, a key pro-inflammatory cytokine involved in the pathogenesis of various inflammatory conditions.
  2. Inhibition of Inflammatory Signaling: By neutralizing IL-17A, secukinumab prevents its interaction with the IL-17 receptor, thereby inhibiting the inflammatory signaling cascade.
  3. Reduction of Inflammatory Mediators: Treatment with secukinumab leads to decreased levels of inflammatory mediators, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and S100 proteins.
  4. Normalization of Keratinocyte Differentiation: In psoriasis, secukinumab helps restore normal keratinocyte differentiation and reduces epidermal hyperplasia.
  5. Modulation of Neutrophil Migration: Secukinumab indirectly reduces neutrophil migration to inflammatory sites by inhibiting IL-17A-induced chemokine production.

Indications

Secukinumab 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.
  • Active Enthesitis-Related Arthritis (ERA): In patients 4 years and older.
  • Active Juvenile Psoriatic Arthritis (JPsA): In patients 2 years and older.

Dosage and Administration

For adult patients:

  • Plaque Psoriasis: 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. For some patients, a dose of 150 mg may be acceptable.
  • Psoriatic Arthritis: With loading dose: 150 mg at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. Without loading dose: 150 mg every 4 weeks. Can be increased to 300 mg if needed.
  • Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis: 150 mg at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter.

For pediatric patients:

  • Plaque Psoriasis (6 years and older):
    • For patients weighing <50 kg: Initial dose of 75 mg at Weeks 0, 1, 2, 3, and 4 followed by 75 mg every 4 weeks.
    • For patients weighing ≥50 kg: Adult dosing regimen applies.
  • Enthesitis-Related Arthritis (4 years and older) and Juvenile Psoriatic Arthritis (2 years and older):
    • For patients weighing <50 kg: 75 mg at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter.
    • For patients weighing ≥50 kg: 150 mg at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter.

Adverse Effects

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

  • Nasopharyngitis
  • Diarrhea
  • Upper respiratory tract infections
  • Rhinitis
  • Oral herpes
  • Pharyngitis
  • Urticaria
  • Rhinorrhea

Serious adverse effects:

  • Infections: Secukinumab may increase the risk of infections. Caution should be exercised when considering its use in patients with chronic infections or a history of recurrent infections.
  • Inflammatory Bowel Disease: New onset or exacerbations of Crohn's disease and ulcerative colitis have been reported. Monitor patients for signs and symptoms of IBD.
  • Hypersensitivity Reactions: Rare cases of anaphylaxis and other serious hypersensitivity reactions have been reported.

Precautions and Contraindications

Contraindications:

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

Precautions:

  1. Infections: Secukinumab may increase the risk of infections. Exercise caution when considering secukinumab for patients with chronic or recurrent infections. Evaluate patients for tuberculosis (TB) prior to initiating treatment.
  2. Inflammatory Bowel Disease: Monitor for signs and symptoms of inflammatory bowel disease. If IBD develops or exacerbates, discontinue secukinumab and initiate appropriate medical management.
  3. Hypersensitivity Reactions: If a serious allergic reaction occurs, discontinue secukinumab immediately and initiate appropriate therapy.
  4. Vaccinations: Avoid use of live vaccines concurrently with secukinumab. Non-live vaccinations received during secukinumab treatment may not elicit an immune response sufficient to prevent disease.
  5. Latex Sensitivity: The removable cap of the Cosentyx sensoready pen and the prefilled syringe contains natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals.
  6. Pregnancy: Limited data available on use in pregnant women. As a precautionary measure, it's preferable to avoid the use of secukinumab during pregnancy.
  7. Breastfeeding: It is unknown whether secukinumab is excreted in human milk. A decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother.
  8. Pediatric Use: Safety and efficacy have been established in pediatric patients for certain indications (as detailed in the Indications section). Caution should be exercised when treating pediatric patients, and regular monitoring is advised.
  9. Geriatric Use: No overall differences in safety or efficacy were observed between older and younger adult patients, but greater sensitivity in some older individuals cannot be ruled out.


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