What is secukinumab (a monoclonal antibody)?

What is Secukinumab?

Secukinumab is a fully human IgG1/κ monoclonal antibody that selectively binds to and neutralizes interleukin-17A (IL-17A), thereby inhibiting its interaction with the IL-17 receptor and blocking the release of proinflammatory cytokines and chemokines. 1

Mechanism of Action

• Secukinumab targets IL-17A, a naturally occurring cytokine involved in normal inflammatory and immune responses that is found at elevated levels in psoriatic plaques, hidradenitis suppurativa lesions, and in the blood of patients with psoriatic arthritis and axial spondyloarthritis 1
• The antibody is produced in recombinant Chinese Hamster Ovary (CHO) cell lines and has a molecular mass of approximately 151 kDa 1
• By neutralizing IL-17A, secukinumab inhibits the inflammatory cascade that drives these chronic inflammatory conditions 1

FDA-Approved Indications

Secukinumab (marketed as Cosentyx) is FDA-approved for multiple inflammatory conditions:

• Moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy 2, 3
• Active psoriatic arthritis in adults 2, 3
• Ankylosing spondylitis (radiographic axial spondyloarthritis) in adults 2, 4
• Non-radiographic axial spondyloarthritis in adults 1
• Active moderate-to-severe hidradenitis suppurativa in adults with inadequate response to conventional systemic therapy 5

Dosing and Administration

For plaque psoriasis, the recommended regimen is 300 mg by subcutaneous injection at weeks 0,1,2,3, and 4, followed by 300 mg every 4 weeks for maintenance. 2

• The 300 mg dose is more effective than 150 mg and is equally safe, though 150 mg may be acceptable for some patients 2
• For hidradenitis suppurativa, the same loading schedule is used (300 mg at weeks 0,1,2,3,4), followed by every 4 weeks, with potential increase to every 2 weeks if inadequate response 5
• Secukinumab is available as prefilled syringes, Sensoready pens, and UnoReady pens for self-administration 1

Clinical Efficacy

Secukinumab demonstrates superior efficacy compared to placebo and comparable biologics:

• At week 16,79% of secukinumab-treated patients achieved PASI 90 compared with 57.6% in the ustekinumab-treated group 2
• The drug is effective across multiple psoriasis subtypes including scalp, nail, palmoplantar, and erythrodermic psoriasis 2
• Long-term efficacy has been demonstrated up to 5 years in psoriasis and psoriatic arthritis, and up to 4 years in ankylosing spondylitis 4, 6
• Continuous every-4-week dosing is more effective than as-needed dosing after the initial 12-week course 2

Safety Profile

Secukinumab has a consistently favorable long-term safety profile across all approved indications:

• The most common adverse events include upper respiratory tract infections, oral herpes, headache, rhinorrhea, diarrhea, nausea, and fatigue 7, 5
• Serious infections occur at low rates (1.2-1.9 per 100 patient-years across indications) 4
• Candida infections (mucosal and cutaneous) have been reported but occur at low rates (0.7-2.2 per 100 patient-years) 8, 4
• Neutralizing anti-secukinumab antibodies are rare (<0.4% of patients) and not associated with loss of efficacy 2
• Weight gain is not an expected side effect of secukinumab therapy 7

Monitoring Requirements

Before initiating secukinumab, tuberculosis screening is required, and baseline complete blood count should be obtained. 8, 5

• Monitor for signs of infection throughout treatment, as secukinumab increases infection risk 8
• Periodic CBC monitoring is necessary to identify potential neutropenia, though most cases are mild, transient, and reversible 8
• Patients with risk factors for inflammatory bowel disease should be monitored, as new cases or exacerbations have been reported 8
• Baseline inflammatory markers (such as CRP) should be considered to assess disease activity 8

Important Contraindications and Precautions

• Active inflammatory bowel disease is a contraindication, as secukinumab has been associated with new cases or exacerbations 5
• Active infections including tuberculosis require consultation with infectious disease specialists before initiation 2
• History of allergic reaction to the therapeutic agent or vehicle is an absolute contraindication 2
• Latent tuberculosis must be screened for and treated before starting therapy 5