What are the recommended dosing schedules for secukinumab, ustekinumab, and ixekizumab in adult patients with moderate-to-severe plaque psoriasis or psoriatic arthritis?

Dosing Schedules for Secukinumab, Ustekinumab, and Ixekizumab

Secukinumab Dosing

Administer secukinumab 300 mg subcutaneously at weeks 0,1,2,3, and 4 (loading phase), followed by 300 mg every 4 weeks indefinitely starting at week 8 for moderate-to-severe plaque psoriasis or psoriatic arthritis. 1

Loading Phase Details

• The loading phase consists of five consecutive weekly 300 mg injections 1
• Each 300 mg dose may be given as a single injection or as two 150 mg injections 1
• Inject in different anatomic sites each week (upper arm, thigh, or abdominal quadrant) and avoid areas with active psoriasis lesions 1

Maintenance Phase

• Continue 300 mg subcutaneously every 4 weeks beginning at week 8 without a predetermined stopping point 1
• The 300 mg dose achieves PASI 90 in 79% of patients by week 16, superior to the 150 mg dose 1
• Clinical response is sustained through at least 52 weeks and up to 5 years with continuous dosing 1

Critical Dosing Errors to Avoid

• Do not extend the dosing interval to every 6 weeks, even in patients achieving early PASI 90 responses; this significantly reduces the likelihood of maintaining PASI 90 1
• Do not use "as-needed" or intermittent dosing after the loading phase; continuous every-4-week dosing is essential for durable efficacy 1
• Do not use the 150 mg dose when 300 mg is appropriate; the higher dose provides markedly greater efficacy with comparable safety 1

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Ustekinumab Dosing

For patients weighing ≤100 kg, administer ustekinumab 45 mg subcutaneously at weeks 0 and 4, then every 12 weeks; for patients >100 kg, use 90 mg at the same schedule. 2

Weight-Based Dosing Algorithm

• ≤100 kg body weight: 45 mg SC at weeks 0,4, then every 12 weeks 2
• >100 kg body weight: 90 mg SC at weeks 0,4, then every 12 weeks 2

Dose Optimization for Inadequate Response

• For suboptimal response, escalate to 90 mg dose (if on 45 mg) or shorten the interval to every 8 weeks 3
• Adding methotrexate or acitretin to ustekinumab may augment efficacy 3

Site-Specific Efficacy

• For palmoplantar psoriasis, the 90 mg dose achieves 67% complete clearance compared to only 9% with 45 mg 3
• For nail psoriasis, ustekinumab produces median 100% improvement in NAPSI scores by week 40, with 44.7% achieving full nail clearance 3

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Ixekizumab Dosing

Ixekizumab achieves PASI 90 in 84% of patients with moderate-to-severe plaque psoriasis, representing one of the highest efficacy rates among biologics. 3

Standard Dosing Regimen

• While specific dosing details are not provided in the guideline excerpts, ixekizumab is recommended as a first-line biologic alongside secukinumab, bimekizumab, and risankizumab for severe plaque psoriasis 3
• Ixekizumab (anti-IL-17 agent) demonstrates PASI 90 response rates of approximately 84% (RR ≈ 30 versus placebo) 3

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Pre-Treatment Screening Requirements (All Three Agents)

Mandatory Screening Before Initiation

• Tuberculosis: Perform PPD skin test or interferon-γ release assay; treat latent TB before starting therapy 1, 2
• Active infections or sepsis: Screen and defer therapy until resolved 1
• Hepatitis B: Screen for infection; untreated hepatitis B is a relative contraindication 1
• Inflammatory bowel disease history: Assess carefully, as secukinumab may exacerbate IBD (choose ustekinumab instead if IBD present) 2

Vaccination Timing

• Administer all live attenuated vaccines at least 2-4 weeks before initiating therapy; live vaccines are absolutely contraindicated once treatment starts 1, 2
• Complete indicated killed vaccines before starting therapy, though immediate treatment need not be delayed for killed vaccines if disease severity warrants 1
• Pneumococcal vaccine is strongly recommended before any biologic therapy 1

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Treatment Selection Algorithm

For Pure Plaque Psoriasis (No Psoriatic Arthritis)

• First choice: Secukinumab 300 mg (achieves 79% PASI 90 at week 16, superior to ustekinumab's 57.6%) 2
• Alternative: Ixekizumab (achieves 84% PASI 90) 3

For Psoriasis with Concurrent Psoriatic Arthritis

• First choice: Ustekinumab (treats both skin and joint symptoms effectively) 2
• Alternative: Secukinumab (also effective for psoriatic arthritis with significant improvements in HAQ-DI scores) 1

For Patients with Inflammatory Bowel Disease History

• First choice: Ustekinumab (secukinumab may worsen IBD and should be discontinued if new-onset or exacerbation occurs) 2, 1

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Safety Monitoring During Treatment

Secukinumab-Specific Monitoring

• Monitor for mucocutaneous candida infections (1.9 events per 100 patient-years); these are typically mild and respond to standard antifungal treatment 1
• Serious infections are rare (0.015 per patient-year) but require temporary discontinuation until resolved 1
• Watch for new-onset or worsening inflammatory bowel disease; discontinue immediately if this occurs 1
• Neutropenia may occur but is usually mild, transient, and reversible 1

Ustekinumab-Specific Monitoring

• Generally well-tolerated with no specific patterns of infection 2
• Ongoing TB monitoring required throughout treatment, even after negative baseline test 3

Common to All Biologics

• Discontinue treatment during active serious infections and do not resume until infection resolves 1
• Less than 1% of patients develop neutralizing antibodies to secukinumab, rarely impacting efficacy 1

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Combination Therapy to Enhance Efficacy

Evidence-Based Combinations

• Adding high-potency topical corticosteroids to any of these biologics can augment efficacy 2
• Calcipotriene/betamethasone dipropionate combined with secukinumab or ustekinumab accelerates plaque clearance 2
• Ustekinumab may be combined with methotrexate, acitretin, or narrowband UVB phototherapy for improved outcomes 2

Combinations to Avoid

• Never combine secukinumab with other biologics; such combinations carry unknown risks 1
• Never use salicylic acid with calcipotriene; the acidic pH inactivates calcipotriene 3