# Safety and immunologic consequences of IL-17A antagonism (infections, hypersensitivity)

## IL-17A antagonists demonstrate a favorable safety profile

IL-17A antagonists demonstrate a favorable safety profile across psoriasis, psoriatic arthritis, and ankylosing spondylitis, with the most consistent safety signal being an increased risk of Candida infections.

- **Candida infection rates varied by indication** (2.2-2.9 per 100 patient-years in psoriasis, 1.5 in psoriatic arthritis, 0.7 in ankylosing spondylitis).
- Serious infection rates remained low (1.2-1.9 per 100 patient-years) with no significant increase compared to placebo.
- Other safety outcomes remained low and stable in long-term follow-up.

## Abstract

Comprehensive pooled analyses including over 12,000 patients with up to 5 years of exposure demonstrated no increase in serious adverse events, infections, or other safety outcomes over time.

## Methods

We analyzed 10 sources from an initial pool of 200, using 9 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question.

- **Records from Elicit search**: n = 200
- **Papers screened out**: n = 190
- **Papers included for extraction**: n = 10

## Infection Outcomes

### Overall Infection Rates
Infection rates varied across studies and indications, with most reporting exposure-adjusted incidence rates per 100 patient-years.

- **Psoriasis**: 1.4 per 100 PY
- **Psoriatic arthritis**: 1.9 per 100 PY
- **Ankylosing spondylitis**: 1.2 per 100 PY

### Fungal Infections
Candida infections emerged as a consistent safety signal across IL-17A antagonist therapy.

- **Secukinumab**: 3.55 per 100 SYs at 300 mg
- **Ixekizumab**: 3.3% incidence rate

### Opportunistic and Other Specific Infections
Opportunistic infections were rare across all indications, with incidence rates below 0.2 per 100 patient-years.

## Hypersensitivity and Immunogenicity Outcomes

### Injection Site Reactions

- Rates range from 0.6 to 1.6 per 100 patient-years.

### Other Safety Outcomes
- **Major adverse cardiovascular events (MACE)** remained low across all indications (below 0.7 per 100 patient-years).
- **Malignancy incidence** remained low and stable across indications.
- **Neutropenia** was identified as a safety signal, with events generally mild and transient.

## Synthesis
### Study Quality Hierarchy and Long-Term Safety
The strongest evidence for IL-17A antagonist safety comes from the large pooled analyses with post-marketing surveillance.
### Mechanistic Explanations
The pattern of predominantly mucocutaneous Candida infections aligns with the role of IL-17A in immunological protection against these infections.