IL-17 and IL-23 Inhibitors: Contraindications, Side Effects, Cost, and Usage
Direct Answer
IL-17 and IL-23 inhibitors are used as monotherapy for moderate-to-severe psoriasis and psoriatic arthritis, with distinct contraindication profiles: IL-17 inhibitors are absolutely contraindicated in active inflammatory bowel disease (IBD), while IL-23 inhibitors have no such restriction and only share the universal contraindication of prior allergic reactions to the therapeutic agent. 1
Contraindications
Absolute Contraindications (Both Classes)
- History of allergic reaction to the therapeutic agents or vehicle 1
IL-17 Inhibitors Specific
- Active or history of inflammatory bowel disease (IBD) - This is critical because IL-17 inhibitors can paradoxically worsen bowel disease 1, 2
- Brodalumab specifically: Recent suicidal behavior or active suicidal ideation 1
IL-23 Inhibitors Specific
- No additional absolute contraindications beyond allergic reactions 1
- Notably, IL-23 inhibitors may actually benefit IBD patients (ustekinumab is FDA-approved for Crohn's disease) 2
Relative Contraindications
- Active febrile illness requiring antibiotics (temporary discontinuation) 1
- Brodalumab: History of suicidal ideation 1
Adverse Effects
IL-17 Inhibitors
Common adverse effects:
- Mucocutaneous Candida infections - most characteristic side effect 1
- Nasopharyngitis and upper respiratory infections 3, 4
- Injection site reactions (particularly ixekizumab: up to 20%) 1
- Headache 3
Serious but rare:
- IBD exacerbation or new-onset IBD 1, 2
- Neutropenia 1
- Hepatotoxicity/elevated liver transaminases 1
- Suicidal ideation and completed suicides (brodalumab only) - requires REMS program enrollment 1
Important caveat: Combination with methotrexate increases infection risk 1
IL-23 Inhibitors
Common adverse effects:
- Increased risk of infections (generally well-tolerated) 1
- Nasopharyngitis 3
- Upper respiratory infections 3
Serious but rare:
- Elevated liver transaminases 1
- No unique adverse events of interest compared to other biologics 1
- No demonstrated IBD exacerbation risk 1, 2
Comparative Safety Profile
Recent 2024 population-based data shows both IL-17 and IL-23 inhibitors are associated with DECREASED risk of several malignancies including non-Hodgkin lymphoma, hepatobiliary cancer, and basal cell carcinoma compared to TNF inhibitors 5. This contradicts earlier concerns about malignancy risk 1.
Monotherapy vs. Combination Use
Both IL-17 and IL-23 inhibitors are FDA-approved and recommended as monotherapy agents 1. The guidelines explicitly state:
- All agents are recommended as monotherapy treatment options 1
- Combination therapy with topical agents, methotrexate, or phototherapy can be considered in partial responders 1
- No published data supports combination therapy for IL-23 inhibitors, but such combinations are not considered unsafe 1
- Combination with methotrexate increases infection risk 1
Clinical pearl: These agents are designed and approved for use as single-agent therapy, unlike older biologics that often required combination approaches.
Cost Considerations
The evidence provided does not include specific cost data. However, in clinical practice:
- All IL-17 and IL-23 inhibitors are high-cost biologics (typically $60,000-80,000+ annually in the US)
- IL-23 inhibitors offer dosing advantage: every 8-12 weeks after loading 1
- IL-17 inhibitors require more frequent dosing: every 2-4 weeks 1
- Less frequent dosing of IL-23 inhibitors may reduce indirect costs (office visits, time off work)
Pretreatment Screening Requirements
Both Classes Require:
- Tuberculosis testing (PPD or Quantiferon Gold) 1
- 2026 update: Routine TB testing is no longer required for IL-17/IL-23 inhibitors per NPF/IPC consensus, except in TB-endemic areas or patients on concomitant immunosuppression 6
- Hepatitis B and C serologic testing 1
- HIV testing at discretion based on risk factors 1
- Medical history evaluation for IBD before starting IL-17 inhibitors 1
Ongoing Monitoring:
- Periodic history and physical examination 1
- Screening for infections 1
- Assessment for IBD symptoms (IL-17 inhibitors) 1
- Periodic assessment for suicidal ideation (brodalumab) - may require more frequent visits 1
- Yearly TB testing only in high-risk patients 1
- Follow-up visits quarterly to twice yearly 1
Efficacy Comparison
Short-term efficacy (12-16 weeks):
IL-17 inhibitors demonstrate superior short-term efficacy 7, 8:
- Bimekizumab, secukinumab, and ixekizumab rank highest 7, 8
- PASI 75 achievement: 83-89% 4
- However, bimekizumab shows less favorable safety profile 7
Long-term considerations:
- IL-23 inhibitors (particularly tildrakizumab) may be promising for sustained control 7
- Interclass switching (IL-17 to IL-23 or vice versa) outperforms intraclass switching 9
Key Clinical Decision Points
Choose IL-17 inhibitors when:
- Rapid clearance is priority (psoriatic arthritis with active joint disease)
- No history of IBD
- Patient can tolerate more frequent injections
- Axial disease component present 10
Choose IL-23 inhibitors when:
- Patient has IBD or IBD risk factors
- Less frequent dosing preferred
- Longer-term safety profile desired
- Patient failed IL-17 inhibitor 9
Avoid IL-17 inhibitors in: