Secukinumab

Approved Indications:

• Plaque Psoriasis (Moderate to Severe):
  Indicated in adults who are candidates for systemic therapy or phototherapy.
• Psoriatic Arthritis (PsA):
  Indicated alone or with methotrexate for active psoriatic arthritis in adults.
• Ankylosing Spondylitis (AS):
  For adults with active radiographic axial spondyloarthritis.
• Non-Radiographic Axial Spondyloarthritis (nr-axSpA):
  In adults with objective signs of inflammation (elevated CRP and/or MRI).
• Hidradenitis Suppurativa (HS):
  Indicated for moderate to severe HS in adult patients.

Off-Label / Clinically Accepted Uses:

• Palmoplantar pustulosis
• Refractory anterior uveitis (under clinical study and specialist guidance)

Route of Administration: Subcutaneous injection (thigh, abdomen, upper arm). Avoid injecting into inflamed or psoriatic skin.

Plaque Psoriasis (Adult):

• Initial Dose: 300 mg (two 150 mg injections) weekly at Weeks 0, 1, 2, 3, and 4
• Maintenance Dose: 300 mg every 4 weeks

Psoriatic Arthritis (Adult):

• With moderate to severe plaque psoriasis: same as psoriasis regimen
• Without moderate to severe psoriasis: 150 mg every 4 weeks; loading dose may be used

Ankylosing Spondylitis (Adult):

• 150 mg subcutaneously every 4 weeks (with or without initial loading doses)

Non-Radiographic Axial Spondyloarthritis (Adult):

• 150 mg every 4 weeks following initial loading (Weeks 0, 1, 2, 3, 4)

Hidradenitis Suppurativa (Adult):

• Initial Dose: 300 mg every week for 5 weeks (Weeks 0–4)
• Maintenance Dose: 300 mg every 4 weeks thereafter

Special Populations:

• Pediatric Use: Not established
• Elderly: No specific adjustment needed; monitor closely
• Renal/Hepatic Impairment: No dose adjustment data available; use with caution

Secukinumab is a fully human IgG1/κ monoclonal antibody that selectively binds to and neutralizes interleukin-17A (IL-17A), a pro-inflammatory cytokine involved in the pathogenesis of autoimmune disorders. By inhibiting IL-17A, it reduces downstream signaling that drives inflammation, keratinocyte proliferation, and joint damage. This mechanism is central to its effectiveness in treating psoriasis, psoriatic arthritis, and spondyloarthritis by restoring immune regulation and reducing inflammation in the skin and joints.

• Absorption: Bioavailability ~73% after subcutaneous injection; Tmax ~5–6 days
• Distribution: Volume of distribution ≈ 7.1 L
• Metabolism: Degraded by lysosomal proteolysis into small peptides and amino acids; not metabolized by CYP450 enzymes
• Elimination: Terminal half-life ~27 days; slow systemic clearance
• Steady-State: Achieved within 20 weeks of once-monthly dosing

• Pregnancy:
  No FDA category under current labeling. Animal data show no direct fetal harm, but human data are limited. Use only if clearly needed after assessing risks and benefits.
• Lactation:
  Unknown if excreted in human milk. Due to the potential for immunosuppression in infants, caution is advised. Monitor breastfed infants for infections or gastrointestinal disturbances.
• Recommendation:
  Avoid use unless no safer alternatives exist. Consider delaying treatment or discontinuing breastfeeding.

• Primary Class: Interleukin-17A Inhibitor
• Subclass: Biologic Disease-Modifying Anti-Rheumatic Drug (bDMARD)
• Type: Human monoclonal antibody (IgG1)

• Known hypersensitivity to Secukinumab or any component of the formulation
• Clinically significant active infections (e.g., tuberculosis, sepsis)
• History of severe allergic reactions to monoclonal antibodies

• Infections:
  Increased risk of upper respiratory infections, candidiasis, and potentially serious infections. Screen for tuberculosis before starting treatment.
• Inflammatory Bowel Disease:
  May cause new-onset or worsen existing Crohn’s disease or ulcerative colitis. Monitor closely.
• Vaccinations:
  Do not administer live vaccines during treatment. Vaccinate before initiating therapy if necessary.
• Hypersensitivity:
  Rare but serious reactions such as anaphylaxis have been reported. Discontinue if severe allergic reaction occurs.
• Monitoring:
  Regular assessment for infections and signs of IBD flare-ups is recommended during treatment.

Common Adverse Effects (≥1%):

• Respiratory: Nasopharyngitis, rhinitis, upper respiratory infections
• Skin: Injection site pain, erythema, pruritus
• Gastrointestinal: Diarrhea, nausea

Serious Adverse Effects:

• Inflammatory bowel disease exacerbation (Crohn’s or ulcerative colitis)
• Opportunistic infections (e.g., oral candidiasis)
• Severe hypersensitivity or anaphylactic reactions

Rare Adverse Effects:

• Neutropenia
• Urticaria or angioedema
• Reactivation of latent tuberculosis

• Live Vaccines:
  Should not be administered concurrently due to risk of infection.
• Immunosuppressants (e.g., other biologics):
  Combination with other biologics or potent immunosuppressants increases infection risk and is not recommended.
• CYP450 Substrates:
  IL-17A inhibition may influence CYP450 enzyme levels. Use caution with narrow therapeutic index drugs (e.g., warfarin, theophylline).

• Expanded Indications:
  FDA and EMA have approved Secukinumab for non-radiographic axial spondyloarthritis and hidradenitis suppurativa in recent years.
• Psoriasis Guidelines (AAD, NICE):
  Secukinumab is now a first-line biologic for moderate to severe plaque psoriasis based on sustained efficacy and safety profile.
• IBD Monitoring:
  Additional precautions recommended due to increased reports of inflammatory bowel disease flares in treated patients.

• Temperature: Store at 2°C to 8°C (refrigerated); do not freeze
• Protection: Keep in original carton to protect from light
• Handling: Allow to reach room temperature (~30 minutes) before injection
• Do Not Shake
• Shelf Life: Follow manufacturer’s expiry date on packaging