IL-23 Inhibitors for Moderate to Severe Plaque Psoriasis, Psoriatic Arthritis, and Crohn's Disease
Overview of Available IL-23 Inhibitors
IL-23 inhibitors represent highly effective first-line biologic therapy for moderate-to-severe plaque psoriasis, with risankizumab demonstrating the strongest efficacy data, achieving 36-45% complete clearance (PASI 100) at week 16. 1
The FDA-approved IL-23 inhibitors include:
- Risankizumab (Skyrizi): Approved for moderate-to-severe plaque psoriasis, active psoriatic arthritis, moderately to severely active Crohn's disease, and moderately to severely active ulcerative colitis 2
- Tildrakizumab: Approved for moderate-to-severe plaque psoriasis 3
- Mirikizumab: Approved for ulcerative colitis 3
- Guselkumab: Approved for plaque psoriasis and ulcerative colitis 3
Plaque Psoriasis Treatment
Risankizumab (First-Line Recommendation)
Dosing Protocol:
- 150 mg subcutaneously at weeks 0 and 4, then every 12 weeks thereafter 1, 4
- This represents the standard induction and maintenance regimen with Grade A evidence 1
Efficacy Benchmarks:
- 36-45% of patients achieve PASI 100 (complete clearance) at week 16 1, 4
- 75% achieve PASI 90 at week 12, compared to only 42% with ustekinumab 1, 4
- Superior efficacy maintained regardless of patient weight, baseline disease severity, prior biologic exposure, or presence of psoriatic arthritis 5
Response Assessment:
- Evaluate treatment response at 12 weeks of continuous therapy to determine definitive positive or negative response 1, 4
- For partial responders at 12 weeks, add topical corticosteroids, vitamin D analogues, methotrexate, or ultraviolet B phototherapy 1
Tildrakizumab (Alternative Option)
Dosing Protocol:
- 100 mg subcutaneous injection at weeks 0 and 4, then every 12 weeks thereafter 6
- Grade A recommendation from AAD-NPF guidelines 6
Efficacy Data:
- 61% achieve PASI 75 at week 12 with 100 mg dose 3, 6
- 66% achieve PASI 75 with 200 mg dose 3, 6
- Superior to etanercept (48% PASI 75 at week 12) 6
- Real-world data confirms efficacy with mean PASI reduction from 15.8 to 1.5 at 12 months 7
Psoriatic Arthritis Treatment
Risankizumab is the only IL-23 inhibitor with FDA approval for active psoriatic arthritis in adults. 2
Clinical Efficacy:
- Demonstrates effectiveness in decreasing swollen and tender joints, clearing psoriatic plaques, and improving quality of life 8
- Efficacy maintained through week 52 in phase 3 trials 8
- Most common adverse event is upper respiratory tract infection 8
Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis)
Risankizumab for Ulcerative Colitis
The AGA strongly recommends risankizumab for moderate-to-severe UC over no treatment (strong recommendation, moderate to high certainty of evidence). 4
Efficacy Data:
- Induction: 18.5% achieve clinical remission vs 6.2% with placebo (RR 3.30,95% CI 2.10-5.18) 3
- Maintenance: 49.5% achieve clinical remission vs 23.9% with placebo (RR 2.04,95% CI 1.57-2.65) 3
- Classified as intermediate efficacy for patients with prior biologic exposure 4
Mirikizumab for Ulcerative Colitis
Efficacy Data:
- Induction: 24.1% achieve clinical remission vs 11.8% with placebo (RR 1.94,95% CI 1.43-2.63) 3
- Maintenance: 49.5% achieve clinical remission vs 23.9% with placebo 3
Guselkumab for Ulcerative Colitis
Efficacy Data:
- Induction: 23.2% achieve clinical remission vs 8.3% with placebo (RR 2.82,95% CI 1.95-4.08) 3
Pre-Treatment Screening Requirements
Before initiating any IL-23 inhibitor, complete the following mandatory screening: 4
- Screen for active infections, tuberculosis, and malignancy at baseline 4
- Complete prophylactic vaccination against pneumococcal and influenza infections 1, 4
- Establish baseline respiratory status if respiratory comorbidities are present 1
- Use extreme caution in patients with pre-existing immunosuppression-related conditions 1, 4
Safety Profile and Monitoring
IL-23 inhibitors demonstrate favorable safety profiles with potentially lower infectious complications compared to TNF antagonists. 4
Common Adverse Events:
- Upper respiratory tract infections (most common) 8
- No serious adverse events reported in real-world tildrakizumab cohort 7
Special Monitoring:
- Monitor vigilantly for respiratory symptoms and infections, particularly in patients with respiratory comorbidities 4
- Limited pregnancy data exist, but safety profile expected to be similar to ustekinumab (no significant increase in adverse pregnancy outcomes) 4
Perioperative Management
Discontinue IL-23 inhibitors approximately 3-4 half-lives before elective surgery: 1, 4
- For risankizumab (half-life ~28 days): discontinue 12-16 weeks before surgery 1, 4
- Resume therapy 1-2 weeks after surgery if no postoperative complications 1
Comparative Positioning
Anti-IL-23 therapy, especially anti-p19 monoclonal antibodies (risankizumab, guselkumab, tildrakizumab), should be considered first-line therapy for moderate-to-severe plaque psoriasis due to superior efficacy and relative safety. 9
Efficacy Hierarchy for Psoriasis:
- Risankizumab: 75% PASI 90 at week 12 1, 4
- Guselkumab: 70-73% PASI 90 at week 16 6
- Tildrakizumab: 61-66% PASI 75 at week 12 3, 6
- Ustekinumab: 42% PASI 90 at week 12 1, 4
Critical Pitfalls to Avoid
- Do not assess treatment failure before 12 weeks of continuous therapy - definitive response requires full 12-week evaluation 1, 6, 4
- Do not assume dose escalation is necessary - IL-23 inhibitors maintain efficacy at standard dosing across weight ranges 5
- Do not withhold combination therapy in partial responders - adding topicals, methotrexate, or phototherapy is safe and effective 3, 1
- Do not overlook tuberculosis screening - mandatory before initiating therapy 4