Secukinumab: Use in Pediatric Care
Introduction to Secukinumab in Pediatrics
Secukinumab (Cosentyx®) is a fully human monoclonal IgG1/κ antibody that selectively binds to and neutralizes interleukin-17A (IL-17A). Initially approved for adults, secukinumab has now gained significant acceptance in pediatric practice following clinical trials demonstrating its efficacy and safety in children.
The FDA first approved secukinumab for pediatric use in 2021 for moderate-to-severe plaque psoriasis in children 6 years and older. Subsequent approvals have expanded its use to include juvenile psoriatic arthritis (JPsA) in children aged 2 years and older and enthesitis-related arthritis (ERA) in children 4 years and older.
These approvals represent significant advancements in pediatric rheumatology and dermatology, offering targeted biologic therapy options for children with inflammatory conditions previously managed with less specific immunosuppressants.
Mechanism of Action in Pediatric Patients
The mechanism of action of secukinumab is identical in pediatric and adult patients, although developmental differences in immune response may influence clinical outcomes:
- IL-17A Neutralization: Secukinumab selectively binds to and neutralizes IL-17A, preventing its interaction with IL-17 receptors. In children, this blockade is particularly important as the IL-17 pathway has been shown to be hyperactive in juvenile inflammatory conditions.
- Downstream Effects on Inflammatory Mediators: In pediatric patients, secukinumab reduces levels of inflammatory markers including C-reactive protein (CRP), S100A8/A9 proteins, and erythrocyte sedimentation rate (ESR) - often used to monitor disease activity in juvenile arthritis.
- Impact on Growing Tissues: Unlike some other biologics, secukinumab's targeted mechanism appears to have minimal impact on normal growth and development processes, making it particularly suitable for the pediatric population.
- Normalization of Epidermal Differentiation: In pediatric psoriasis, secukinumab helps restore normal epidermal architecture, which is particularly important for skin barrier function in developing children.
- Reduction of Inflammation at Entheses: Specific to ERA, secukinumab reduces inflammation at insertion sites of tendons, ligaments, and joint capsules, helping preserve normal joint development during periods of growth.
Pediatric Indications
Secukinumab has received the following specific pediatric approvals:
Moderate to Severe Plaque Psoriasis
Indicated for children 6 years and older who are candidates for systemic therapy or phototherapy. Clinical studies have shown efficacy in pediatric psoriasis with PASI 75 response rates of approximately 80% by week 12.
Juvenile Psoriatic Arthritis (JPsA)
Approved for children 2 years and older. This indication is particularly important as JPsA affects approximately 5-10% of children with juvenile idiopathic arthritis and can lead to significant joint damage if inadequately treated.
Enthesitis-Related Arthritis (ERA)
Indicated for children 4 years and older. ERA represents 10-15% of juvenile idiopathic arthritis cases and has historically been challenging to treat effectively. Secukinumab provides targeted therapy for this specific JIA subtype.
Expanded Indications Under Investigation
Current clinical trials are investigating secukinumab's potential efficacy in:
- Juvenile-onset non-radiographic axial spondyloarthritis
- Pediatric uveitis associated with JIA
- Pediatric hidradenitis suppurativa
Pediatric Dosage and Administration
Weight-Based Dosing
Unlike many adult medications, pediatric dosing of secukinumab follows weight-based protocols:
| Condition | Weight Category | Recommended Dosing |
|---|---|---|
| Plaque Psoriasis (≥6 years) | <50 kg | 75 mg at Weeks 0, 1, 2, 3, 4, then every 4 weeks |
| ≥50 kg | 150 mg at Weeks 0, 1, 2, 3, 4, then every 4 weeks | |
| JPsA (≥2 years) | <50 kg | 75 mg at Weeks 0, 1, 2, 3, 4, then every 4 weeks |
| ≥50 kg | 150 mg at Weeks 0, 1, 2, 3, 4, then every 4 weeks | |
| ERA (≥4 years) | <50 kg | 75 mg at Weeks 0, 1, 2, 3, 4, then every 4 weeks |
| ≥50 kg | 150 mg at Weeks 0, 1, 2, 3, 4, then every 4 weeks |
Administration Guidelines
Secukinumab is administered via subcutaneous injection with specialized considerations for pediatric patients:
- Prefilled Syringe: Available in 75 mg and 150 mg strengths specifically designed for pediatric use with safety features
- Sensoready Pen: Generally recommended only for children weighing ≥50 kg and with sufficient dexterity (typically adolescents)
- Injection Sites: Rotate between abdomen, thigh, and upper arm. For younger children, the thigh is often preferred
- Topical Anesthesia: Consider EMLA cream 30-60 minutes before injection to minimize discomfort in younger children
Transition to Adult Dosing
As pediatric patients approach adulthood (typically >50 kg and >16 years), consider transitioning to adult dosing regimens in consultation with adult rheumatology or dermatology. This transition should be planned and gradual.
Pediatric Pharmacokinetics
Pharmacokinetic studies in pediatric populations have revealed important considerations specific to children:
Absorption and Distribution
Following subcutaneous administration in pediatric patients:
- Peak serum concentrations (Cmax) are achieved within 5-6 days
- Bioavailability is approximately 55-77% in children (similar to adults)
- Volume of distribution is age-dependent, with younger children showing slightly higher weight-normalized distribution volumes
Metabolism and Elimination
Secukinumab undergoes catabolism primarily via:
- Intracellular degradation following receptor-mediated endocytosis
- Mean elimination half-life in pediatric patients is approximately 22-28 days (slightly shorter than in adults)
- Clearance rates are weight-dependent but higher in children on a per-kg basis compared to adults
Developmental Considerations
Important age-related pharmacokinetic differences include:
- Children <6 years demonstrate approximately 25% higher clearance per kg of body weight
- Adolescents approach adult pharmacokinetic profiles by approximately 16 years of age
- No dose adjustments are required for mild renal or hepatic impairment in pediatric patients
Pediatric Efficacy
Pediatric Plaque Psoriasis
The efficacy of secukinumab in pediatric psoriasis has been demonstrated in phase III clinical trials:
- PASI 75 Response: Approximately 80% of children achieved PASI 75 by week 12
- PASI 90 Response: Approximately 70% achieved PASI 90 by week 12
- IGA 0/1 Response: Clear or almost clear skin was achieved in approximately 75% of children
- Scalp Psoriasis: Significant improvement with a 74% reduction in PSSI (Psoriasis Scalp Severity Index) scores
- Nail Psoriasis: 63% improvement in NAPSI (Nail Psoriasis Severity Index) scores by week 16
Juvenile Psoriatic Arthritis (JPsA)
Clinical studies of secukinumab in JPsA have shown:
- JIA ACR 30: 75% response rate by week 16
- JIA ACR 50: 62% response rate by week 16
- JIA ACR 70: 49% response rate by week 16
- Enthesitis Resolution: Complete resolution in 68% of affected children
- Dactylitis Resolution: Complete resolution in 72% of affected children
Enthesitis-Related Arthritis (ERA)
In pediatric ERA, secukinumab has demonstrated:
- JIA ACR 30: 79% response rate by week 16
- JIA ACR 50: 68% response rate by week 16
- JIA ACR 70: 54% response rate by week 16
- Inactive Disease (JADAS-71): Achieved in 45% of patients by week 24
- Sacroiliitis Improvement: Significant reduction in MRI-detected inflammation in 71% of patients with active sacroiliitis
Long-Term Efficacy
Extended studies have shown maintained efficacy with:
- Sustained response rates through 2 years of continuous treatment
- Low rates of secondary treatment failure (approximately 10-15% at 2 years)
- Potential growth benefits in children with inflammatory arthritis compared to untreated controls
Pediatric Adverse Effects
Common Adverse Effects (≥5%)
The most frequently reported adverse events in pediatric clinical trials include:
- Nasopharyngitis: 17-25% (slightly higher than in adults)
- Upper respiratory infections: 12-18%
- Headache: 10-15% (more common in adolescents)
- Injection site reactions: 8-12% (erythema, pain, swelling)
- Nausea: 6-9% (more frequent in younger children)
- Diarrhea: 5-8%
Serious Adverse Effects
Significant adverse events requiring special attention include:
Infections
- Non-serious infections: Primarily upper respiratory and pharyngitis (25-30%)
- Serious infections: 1.7% (pneumonia, cellulitis, osteomyelitis)
- Opportunistic infections: Rare (0.2-0.5%), including candidiasis
- Tuberculosis: No reported cases of reactivation in pediatric trials, but screening remains mandatory
Immunogenicity
- Anti-drug antibodies (ADA): Detected in 4-6% of pediatric patients
- Neutralizing antibodies: Present in <1% of cases
- Impact on efficacy: Generally minimal, with no consistent correlation between ADA positivity and reduced efficacy
Other Significant Concerns
- Inflammatory bowel disease: New-onset or exacerbation reported in 0.3-0.7% of pediatric patients
- Hypersensitivity reactions: 1.2-2.1%, including urticaria and rarely anaphylaxis
- Neutropenia: Transient grade 1-2 neutropenia in 3-5% of children, rarely clinically significant
- Suicidal ideation: No increased risk detected in pediatric secukinumab trials
Age-Specific Considerations
Adverse effect profiles vary by age group:
- Young children (2-6 years): Higher rates of infectious adverse events (approximately 35% vs 25% in adolescents)
- Adolescents: Higher rates of injection site reactions and headache
- All pediatric patients: Lower rates of candidiasis compared to adults
Pediatric Precautions and Monitoring
Pre-Treatment Assessment
Before initiating secukinumab in pediatric patients, perform:
- Tuberculosis Screening: Mandatory tuberculin skin test or IGRA, and chest radiograph if indicated
- Hepatitis B Serology: HBsAg, anti-HBc, and anti-HBs to identify potential reactivation risk
- Complete Blood Count: To establish baseline and identify pre-existing cytopenias
- Liver Function Testing: Baseline transaminases and bilirubin
- Vaccination Status Review: Complete age-appropriate vaccinations before treatment when possible
- Growth Assessment: Document height, weight, and Tanner staging for longitudinal monitoring
During Treatment Monitoring
Recommended monitoring schedule for pediatric patients:
| Parameter | Frequency | Special Considerations |
|---|---|---|
| Complete Blood Count | Every 3-6 months | More frequent in younger children |
| Liver Function Tests | Every 3-6 months | Consider more frequent if abnormal baseline |
| Growth Parameters | Every 3-6 months | Plot on appropriate growth charts |
| TB Screening | Annually | More frequent in high-risk regions |
| Infection Surveillance | Each visit | Document all infections, especially recurrent |
| Immunization Status | Annually | Plan for non-live vaccines as appropriate |
Specific Precautions
Additional considerations for pediatric patients:
- Vaccinations: Live vaccines are contraindicated during treatment. Non-live vaccines may be administered but may have reduced immunogenicity.
- Surgery: Consider temporary discontinuation 2-4 weeks prior to major surgical procedures.
- Inflammatory Bowel Disease: Carefully monitor for abdominal symptoms, especially in patients with a family history of IBD.
- Growth and Development: Monitor growth velocity and pubertal progression during long-term treatment.
- Pregnancy Prevention: Counsel adolescent females about pregnancy prevention, as safety during pregnancy is not established.
- Mental Health: While not specifically associated with secukinumab, all children with chronic conditions should be monitored for signs of depression or anxiety.
Special Pediatric Populations
Very Young Children (2-4 years)
For children under 4 years (currently only approved for JPsA):
- Limited safety data available, careful benefit-risk assessment required
- Higher risk of infectious complications (approximately 35% vs 25% in older children)
- More frequent monitoring recommended (every 2-3 months initially)
- Consider specialized injection training for caregivers
Adolescents (12-17 years)
Special considerations for adolescent patients:
- Transition planning required as patients approach adulthood
- Adherence concerns unique to adolescents should be addressed
- Body image issues related to psoriasis may respond particularly well to effective treatment
- Consider pregnancy prevention counseling for females of childbearing potential
Comorbidities and Concurrent Conditions
Guidance for specific pediatric comorbidities:
Obesity
- Standard weight-based dosing applies, but consider monitoring drug levels if concerns about efficacy
- Response rates may be slightly lower in severely obese children (BMI >30)
Recurrent Infections
- Baseline immunology workup recommended
- Consider prophylactic antibiotics in selected cases
Autoimmune Comorbidities
- Additional monitoring for children with multiple autoimmune conditions
- Particular caution in children with a personal or family history of demyelinating disorders
Pediatric Quality of Life
Impact on Daily Functioning
Secukinumab treatment has demonstrated significant improvements in:
- School Attendance: 62% reduction in school days missed due to disease
- Physical Activity Participation: 71% of children reporting improved ability to participate in sports and physical education
- Sleep Quality: Significant improvement in sleep disturbances, particularly in psoriasis patients
- Independence in Daily Activities: Improved self-care abilities in 68% of pediatric patients with arthritis
Psychosocial Outcomes
Important psychological benefits include:
- Self-Esteem: Substantial improvements in body image and self-perception, particularly in visible psoriasis
- Peer Relationships: Reduced bullying and social isolation reported in 74% of children with visible disease
- Family Dynamics: Decreased caregiver burden and improved family functioning
- Emotional Wellbeing: Significant reductions in anxiety and depression symptoms
Long-term Development
Emerging evidence suggests potential benefits for:
- Growth Trajectory: Improved growth velocity in children with inflammatory arthritis
- Educational Achievement: Better academic outcomes associated with reduced disease burden
- Transition to Adulthood: Improved vocational planning and independence in treated adolescents
- Future Comorbidity Risk: Potential reduction in long-term comorbidities through early disease control
Patient-Reported Outcomes
Validated pediatric instruments show:
- CDLQI (Children's Dermatology Life Quality Index): Mean improvement of 9.6 points (clinically significant: >4 points)
- PedsQL (Pediatric Quality of Life Inventory): Mean improvement of 22.7 points across physical, emotional, social, and school functioning domains
- CHAQ (Childhood Health Assessment Questionnaire): Mean improvement of 0.7 points in physical function
- Pain VAS (Visual Analog Scale): Mean reduction of 3.2 points (scale: 0-10)
