Monoclonal Agents for Moderate to Severe Psoriasis
Primary Recommendation
For moderate to severe plaque psoriasis, secukinumab (Cosentyx) is the superior first-line monoclonal antibody, achieving 79% PASI 90 response at week 16 compared to 57.6% with ustekinumab (Stelara), with this superiority maintained through 52 weeks. 1, 2, 3, 4
Treatment Selection Algorithm
First-Line Monoclonal Agent Selection
Choose Secukinumab (IL-17A inhibitor) if:
- Pure plaque psoriasis without psoriatic arthritis 1
- Goal is maximum skin clearance (PASI 90/100) 2, 3
- Palmoplantar plaque psoriasis or nail involvement (Grade A recommendation) 1
- Faster response needed (50% achieve PASI 75 by week 4 vs. 20.6% with ustekinumab) 3
Choose Ustekinumab (IL-12/23 inhibitor) if:
- Concurrent psoriatic arthritis (Grade A recommendation for this indication) 5
- History of inflammatory bowel disease (secukinumab may worsen IBD) 1
- Patient weighs >100 kg and prefers weight-based dosing flexibility 5, 6
- Inadequate response to other biologics and need dose escalation options (can increase to 90 mg or shorten interval to every 8 weeks) 5
Dosing Protocols
Secukinumab Dosing
- Loading phase: 300 mg subcutaneously at weeks 0,1,2,3, and 4 1
- Maintenance: 300 mg every 4 weeks starting at week 8 1
- Note: 300 mg dose is more effective than 150 mg and should be prioritized 1
Ustekinumab Dosing
- For patients ≤100 kg: 45 mg subcutaneously at weeks 0 and 4, then every 12 weeks 5, 6
- For patients >100 kg: 90 mg subcutaneously at weeks 0 and 4, then every 12 weeks 5, 6
- Dose escalation option: Increase to 90 mg (if on 45 mg) or shorten interval to every 8 weeks for inadequate responders 5
Comparative Efficacy Data
PASI 90 Response Rates at Week 16
Speed of Response (PASI 75 at Week 4)
Complete Clearance (PASI 100 at Week 16)
Long-Term Efficacy (52 Weeks)
Pre-Treatment Screening Requirements
Mandatory Screening for Both Agents
- Tuberculosis screening: PPD, T-Spot, or QuantiFERON-Gold test required before initiation 5, 1
- Active infection assessment: Screen for active infections or sepsis; do not initiate during active infection 1
- Hepatitis B screening: Check hepatitis B surface antigen and core antibody; untreated hepatitis B is a relative contraindication 5, 1
Additional Considerations for Secukinumab
- Inflammatory bowel disease history: Assess carefully as secukinumab may increase IBD events 1
Baseline Laboratory Monitoring
- CBC with differential 5
- Complete metabolic profile 5
- Chest radiograph if tuberculosis test is positive 5
Special Populations and Indications
Psoriatic Arthritis
- Ustekinumab: Grade A recommendation, FDA-approved 5
- Secukinumab: Grade A recommendation, FDA-approved 1
Nail Psoriasis
- Ustekinumab: Grade B recommendation; median NAPSI improvement 42.5% at week 16,86.3% at week 28,100% at week 40 5
- Secukinumab: Grade A recommendation for moderate-to-severe nail involvement 1
Palmoplantar Plaque Psoriasis
- Ustekinumab: Grade B recommendation; 35% clearance at 16 weeks, with 67% clearance in patients receiving 90 mg dose 5
- Secukinumab: Grade A recommendation 1
Scalp Psoriasis
Pustular and Erythrodermic Psoriasis
- Ustekinumab: Grade C recommendation; limited evidence for inverse and guttate psoriasis 5
Safety Profile and Monitoring
Common Adverse Events with Secukinumab
- Mucocutaneous candida infections: 1.9 per 100 patient-years, typically mild and responsive to standard treatment 1
- Serious infections: 0.015 per patient-year; require treatment discontinuation until resolved 1
- Neutropenia: Usually mild, transient, and reversible 1
- Immunogenicity: <1% develop antibodies through 52 weeks 1
Common Adverse Events with Ustekinumab
- Generally well tolerated with no specific patterns of infection 7
- Infection rates remain stable with cumulative exposure 7
Contraindications and Precautions
- Both agents: Active tuberculosis, active serious infections 5, 1
- Secukinumab specifically: Active inflammatory bowel disease (may worsen) 1
- Ustekinumab: No increased risk of solid tumor or lymphoreticular malignancy as monotherapy 5
Combination Therapy Options
With Topical Agents
- Both secukinumab and ustekinumab: Can combine with high-potency topical corticosteroids with or without vitamin D analogues to augment efficacy 5, 1
- Note: Published safety data on combinations is limited 1
With Conventional Systemics (Ustekinumab Only)
- Methotrexate: Grade B recommendation for combination 5
- Acitretin: Grade B recommendation for combination 5
- Narrowband UVB phototherapy: Grade B recommendation for combination 5
- Apremilast: Grade C recommendation for combination 5
- Cyclosporine: Grade C recommendation for combination 5
Avoid Biologic-Biologic Combinations
- No evidence supports combining monoclonal antibodies; such combinations carry unknown risks 1
Vaccination Recommendations
Before Starting Either Agent
- Live attenuated vaccines: Must be administered at least 2-4 weeks before initiating therapy; absolutely contraindicated once treatment starts 1
- Killed vaccines: Complete all indicated killed vaccines before starting, but starting the biologic without delay is acceptable if disease severity warrants immediate treatment 1
Specific Vaccines
- Pneumococcal vaccine: Strongly recommended before starting any biologic 1
- Annual influenza vaccination: Recommended; IL-17 inhibitors and ustekinumab do not interfere with immune response 1
- COVID-19 vaccines: Should be administered as soon as eligible; IL-17 inhibitors do not significantly impair vaccine response 1
Critical Clinical Pitfalls to Avoid
Do Not Use Systemic Corticosteroids
- Prednisone and other systemic corticosteroids are not standard of care for psoriasis and have poor long-term efficacy with significant safety concerns 8
Do Not Inject into Active Psoriasis Lesions
- Avoid injecting secukinumab into areas of skin showing active psoriasis 1
Do Not Delay Treatment for Latent TB
- If latent TB is detected, consider anti-tuberculosis therapy before or concurrent with biologic initiation after infectious disease consultation 5, 1
Monitor for IBD with Secukinumab
- If new-onset or exacerbation of inflammatory bowel disease occurs, discontinue secukinumab 1