Ixekizumab Injection: Clinical Uses and Dosing
Primary Indications
Ixekizumab is FDA-approved and strongly recommended for moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, and for psoriatic arthritis. 1, 2
Core Approved Uses (Strength A Recommendations):
- Moderate-to-severe plaque psoriasis as monotherapy in adults 1
- Psoriatic arthritis in patients with plaque psoriasis 1
- Ankylosing spondylitis (FDA approved 2019) 2, 3
- Non-radiographic axial spondyloarthritis 2
Additional Psoriasis Subtypes (Strength B Recommendations):
- Scalp psoriasis (78% achieved complete resolution by week 48) 1
- Nail psoriasis (51% achieved complete resolution by week 48) 1
- Erythrodermic psoriasis 1
- Generalized pustular psoriasis 1
- Genital psoriasis (73% improvement at 12 weeks vs 8% placebo) 1
Standard Dosing Regimen
Adult Plaque Psoriasis:
Initial Phase (Weeks 0-12):
Maintenance Phase (After Week 12):
- 80 mg every 4 weeks (standard maintenance) 1
- 80 mg every 2 weeks may be required for some patients to maintain response 1, 4
Pediatric Dosing (Ages 6 to <18 years):
- Weight >50 kg: Same as adult dosing 2
- Weight 25-50 kg: Adjusted dosing based on weight 2
- Weight <25 kg: Limited data available 2
Mechanism and Pharmacokinetics
Ixekizumab is a humanized IgG4 monoclonal antibody that selectively neutralizes IL-17A, inhibiting the release of proinflammatory cytokines and chemokines 2. Key pharmacokinetic properties include:
- Peak concentration: Approximately 4 days post-dose 2
- Steady-state: Achieved by Week 8 with Q2W dosing 2
- Half-life: 13-15 days 2, 5
- Bioavailability: 60-81% subcutaneously (highest when injected in thigh) 2
Efficacy Benchmarks
At 12 weeks with standard dosing 1, 6:
- PASI 75: Achieved in 89% of patients
- PASI 90: Achieved in 70-86% of patients 5
- PASI 100: Achieved in 6.9-13% of patients 7
- sPGA 0/1: Achieved in 78.6% of patients 4
Response is superior to etanercept and comparable to other IL-17 inhibitors 1, 6.
Important Safety Considerations
Common Adverse Events:
- Injection site reactions: Occur in up to 10% during first 12 weeks (similar to etanercept) 1, 3
- Mucocutaneous Candida infections: 1.9 per 100 patient-years, easily managed and rarely require discontinuation 1, 3
Critical Contraindications and Warnings:
Avoid ixekizumab in patients with active or history of inflammatory bowel disease (IBD) due to risk of reactivation or worsening 1. This is a class effect of IL-17 inhibitors and represents the most significant safety concern 3, 6.
Immunogenicity:
- Neutralizing antibodies: Detected in up to 17% of patients 1, 3
- These antibodies are associated with reduced drug concentrations and loss of efficacy 1
Drug Interactions
No clinically significant interactions with the following 2:
- Methotrexate
- Oral corticosteroids
- NSAIDs
- Conventional DMARDs (sulfasalazine)
- CYP1A2, CYP2C9, CYP2C19, or CYP3A substrates
Potential interaction with CYP2D6 substrates cannot be ruled out due to high variability 2.
Combination Therapy
While no published data exist on combination therapy with topical or systemic agents, there is no reason to consider such combinations unsafe 1. Topical corticosteroids or other adjunctive therapies can be added for partially responding patients 1.
Treatment Response Assessment
Definitive response should be assessed after 12 weeks of continuous therapy 1. For patients with inadequate response:
- Consider adding topical corticosteroids, methotrexate, or ultraviolet light 1
- Consider dose escalation to 80 mg every 2 weeks if on Q4W maintenance 1, 4