Secukinumab

Usage

Secukinumab is prescribed for the treatment of moderate to severe plaque psoriasis in adults, psoriatic arthritis, ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), hidradenitis suppurativa (HS), and specific types of juvenile idiopathic arthritis (JIA) including enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). It is classified as an interleukin-17A (IL-17A) inhibitor, a type of biologic medication that targets a specific part of the immune system. Secukinumab works by selectively binding to and neutralizing IL-17A, a cytokine that plays a key role in inflammatory processes associated with these conditions. By inhibiting IL-17A, secukinumab reduces inflammation and the resulting symptoms.

Alternate Names

Secukinumab is also known by the brand name Cosentyx.

How It Works

Pharmacodynamics: Secukinumab binds with high affinity to IL-17A, preventing it from interacting with its receptor. This leads to a decrease in the production of pro-inflammatory cytokines, chemokines, and other mediators involved in the pathogenesis of psoriasis, psoriatic arthritis, AS, nr-axSpA, HS, and JIA.

Pharmacokinetics:

• Absorption: Administered subcutaneously, secukinumab reaches peak serum concentration within 5 to 6 days. Bioavailability ranges from 55% to 77%.
• Metabolism: As a monoclonal antibody, secukinumab is primarily catabolized through protein degradation pathways into small peptides and amino acids, similar to endogenous IgG. There is no evidence suggesting involvement of CYP450 enzymes.
• Elimination: Secukinumab exhibits nonlinear pharmacokinetics. At higher concentrations, elimination occurs predominantly through a non-saturable linear pathway, while at lower concentrations, a saturable non-linear pathway becomes more important. The terminal half-life is approximately 27 days.

Mode of Action: Secukinumab’s mode of action involves receptor antagonism. It specifically targets the IL-17A receptor, thus blocking the downstream effects of IL-17A. This inhibits the inflammatory cascade that leads to the symptoms of the targeted conditions. No direct enzyme inhibition or neurotransmitter modulation is associated with its mechanism.

Dosage

Standard Dosage

Adults:

• Plaque Psoriasis, Psoriatic Arthritis, AS, nr-axSpA, HS: 300 mg (two 150 mg injections) administered subcutaneously at weeks 0, 1, 2, 3, and 4, followed by 300 mg every 4 weeks. In some cases, 150 mg may be sufficient, or for HS patients, 300 mg every 2 weeks can be considered if the response is inadequate.
• Psoriatic Arthritis (patients with inadequate response to anti-TNFα therapy): 300 mg at weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks.
• Ankylosing Spondylitis: 150mg once weekly for 5 weeks then once monthly thereafter. Review treatment for response after 16 weeks. Consider increasing the dose to 300mg if active disease persists.

Children (6 years and older):

• Plaque Psoriasis, JIA (ERA, JPsA): Dosage is weight-based:
  • < 25 kg: 75 mg subcutaneously at weeks 0, 1, 2, 3, and 4, followed by 75 mg every 4 weeks.
  • 25 kg to < 50 kg: 75 mg subcutaneously at weeks 0, 1, 2, 3, and 4, followed by 75 mg every 4 weeks. The dose may be increased to 150mg as per doctor’s advice.
  • ≥ 50 kg: 150 mg subcutaneously at weeks 0, 1, 2, 3, and 4, followed by 150 mg every 4 weeks. The dose may be increased to 300mg as per doctor’s advice.

Special Cases:

• Elderly Patients: No dose adjustment is typically required.
• Patients with Renal Impairment: No dose adjustment is typically required.
• Patients with Hepatic Dysfunction: No dose adjustment is typically required.
• Patients with Comorbid Conditions: Evaluate on a case-by-case basis, considering the specific comorbidity and potential drug interactions.

Clinical Use Cases

Secukinumab’s current indicated uses do not include intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest.

Side Effects

Common Side Effects:

• Upper respiratory infections (nasopharyngitis, common cold)
• Diarrhea
• Fatigue
• Runny nose
• Headache.

Rare but Serious Side Effects:

• Serious infections (e.g., tuberculosis, candidiasis)
• Allergic reactions (including anaphylaxis)
• Exacerbation of inflammatory bowel disease (IBD)
• Neutropenia.

Long-Term Effects:

The long-term safety profile of secukinumab is still under investigation, but potential risks include increased susceptibility to infections and the possible development of autoimmune disorders.

Adverse Drug Reactions (ADR):

Clinically significant ADRs include anaphylaxis, serious infections, and new or worsening IBD. These require prompt discontinuation of the drug and appropriate medical intervention.

Contraindications

• Hypersensitivity to secukinumab or any of its excipients
• Active, clinically important infection (e.g., active tuberculosis).

Drug Interactions

• Live vaccines: Avoid concomitant use of live vaccines due to the risk of reduced vaccine effectiveness and increased risk of infection. Non-live vaccines can be administered.
• Immunosuppressants: Concomitant use with immunosuppressants may increase the risk of infection.
• CYP450 substrates: Although secukinumab is not metabolized by CYP450 enzymes, it may indirectly affect the levels of CYP450 substrates through its anti-inflammatory effects. Monitor patients on concomitant CYP450 substrates, especially those with a narrow therapeutic index (e.g., warfarin, cyclosporine), and adjust dosages as needed.

Pregnancy and Breastfeeding

• Pregnancy: Secukinumab is a Pregnancy Category B drug. Animal studies have not shown harm to the fetus, but there are limited human data. Use only if the potential benefit outweighs the potential risk. It is generally recommended to avoid secukinumab during pregnancy as a precautionary measure.
• Breastfeeding: It is unknown if secukinumab is excreted in human milk. Exercise caution when administering to breastfeeding women. Consider the benefits of breastfeeding for the child and the benefits of treatment for the woman when deciding whether to discontinue breastfeeding or secukinumab treatment.

Drug Profile Summary

• Mechanism of Action: Interleukin-17A inhibitor.
• Side Effects: Upper respiratory infections, diarrhea, neutropenia, serious infections, allergic reactions.
• Contraindications: Hypersensitivity, active serious infection.
• Drug Interactions: Live vaccines, immunosuppressants, certain CYP450 substrates.
• Pregnancy & Breastfeeding: Use with caution. Potential risks exist for both the fetus and nursing infants.
• Dosage: See detailed dosage guidelines above.
• Monitoring Parameters: Monitor for signs of infection, including tuberculosis and IBD. Monitor complete blood count, including neutrophil count, regularly.

Popular Combinations

Secukinumab is often used as monotherapy. However, in some cases, it may be combined with other non-biologic DMARDs (disease-modifying antirheumatic drugs) like methotrexate for psoriatic arthritis if the response to secukinumab alone is inadequate. The combination should be used with caution, carefully weighing the risks and benefits, particularly the increased risk of infections.

Precautions

• General Precautions: Screen for latent tuberculosis and infections before starting treatment. Monitor for signs and symptoms of infection during treatment.
• Specific Populations: See pregnancy and breastfeeding information above. For children, dose based on weight and age. For elderly patients, monitor for comorbidities and drug interactions.
• Lifestyle Considerations: No specific lifestyle restrictions are associated with secukinumab, but maintaining a healthy lifestyle, including good hygiene and balanced diet, may be beneficial to support overall health.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Secukinumab?

A: The recommended dosage varies depending on the condition being treated and the patient’s age and weight. See detailed dosage guidelines above.

Q2: How is Secukinumab administered?

A: Secukinumab is administered via subcutaneous injection.

Q3: What are the most common side effects of Secukinumab?

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

Q4: Can Secukinumab be used during pregnancy or breastfeeding?

A: Secukinumab should be used with caution during pregnancy and breastfeeding. Consult the detailed section above and discuss with the patient.

Q5: What are the contraindications for using Secukinumab?

A: Contraindications include hypersensitivity to secukinumab and active, serious infections such as active tuberculosis.

Q6: How does Secukinumab interact with other medications?

A: Secukinumab may interact with live vaccines, immunosuppressants, and some CYP450 substrates.

Q7: How long does it take for Secukinumab to start working?

A: It may take several weeks or even months for patients to experience the full benefit of Secukinumab.

Q8: What should patients do if they miss a dose of Secukinumab?

A: Patients should administer the missed dose as soon as they remember and then consult their doctor to adjust the schedule as needed.

Q9: Are there any long-term risks associated with Secukinumab use?

A: Long-term risks are still under investigation, but they may include an increased risk of infections.

Q10: What are the monitoring parameters for patients taking Secukinumab?

A: Patients should be monitored for signs of infection, including tuberculosis and IBD, and complete blood count, including neutrophil count.