# IL-17A Antagonism: Safety and Immunologic Impacts

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

IL-17A antagonists demonstrate a favorable safety profile with the primary immunologic consequence being an increased risk of mild-to-moderate mucocutaneous Candida infections, while serious infections, opportunistic infections, and hypersensitivity reactions remain uncommon, and other safety outcomes stable over long-term follow-up.

## Abstract

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), were predominantly mild-to-moderate and mucocutaneous, and showed a dose-response relationship with secukinumab (3.55 per 100 subject-years at 300 mg versus 1.85 at 150 mg). In contrast, serious infection rates remained low (1.2-1.9 per 100 patient-years) with no significant increase compared to placebo, opportunistic infections were rare (<0.2 per 100 patient-years), and no tuberculosis reactivation cases occurred in pooled clinical trials. Hypersensitivity reactions were uncommon, with injection site reactions occurring at low rates (0.6-1.6 per 100 patient-years with secukinumab), though rates varied substantially between different IL-17A antagonists. Anti-drug antibody development occurred in less than 1% of patients without clinical consequences.

## 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

## Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of  [Semantic Scholar](https://www.semanticscholar.org/) and [OpenAlex](https://openalex.org/).

We ran this query: “Safety and immunologic consequences of IL-17A antagonism (infections, hypersensitivity)”

The search returned 200 total results from Elicit.

We retrieved 200 papers most relevant to the query for screening.

## Screening

We screened in sources based on their abstracts that met several criteria:  
- **IL-17A Antagonist Intervention**: Does this study involve patients treated with IL-17A antagonists?  
- **Safety Outcomes Reported**: Does this study report safety outcomes related to infections, hypersensitivity reactions, or other immunologic consequences?  
- **Appropriate Study Design**: Is this study a randomized controlled trial, observational study, or systematic review?  
- **Human Subjects**: Does this study involve human subjects of any age?  
- **Approved Indications**: Does this study involve patients with approved indication for IL-17A antagonists?  
- **Clinical Research**: Is this clinical research?  
- **Adequate Sample Size**: Is the sample size adequate?  
- **Safety Data Inclusion**: Does this study report safety data?  
- **Original Research Publication**: Is this a full research publication?

## Data extraction

We extracted data columns related to IL-17A antagonists regarding patient population, study design, infection outcomes, hypersensitivity reactions, and other safety outcomes among others.

## Results

### Characteristics of Included Studies

This review included 10 sources comprising primary randomized controlled trials and pooled analyses with post-marketing surveillance data examining IL-17A antagonists across multiple indications.

| Study  | Study type  | Indication(s)  | IL-17 inhibitor(s)  | Sample size | Follow-up duration |
| ------ | ----------- | --------------- | ------------------- | ----------- | ------------------ |
| P. Mease et al., 2015 | Phase 3 RCT | Psoriatic arthritis | Secukinumab 150 mg, 75 mg | 606 patients | Mean 438.5 days |
| A. Deodhar et al., 2019 | Pooled clinical trials | Psoriasis, psoriatic arthritis, ankylosing spondylitis | Secukinumab 75, 150, 300 mg | 7,355 patients | Up to 5 years |

### Infection Outcomes

#### Overall Infection Rates

Infection rates varied across studies and indications, with lower serious infection rates recorded.

| Study | Indication | Serious infections |
|-------|------------|-------------------|
| A. Deodhar et al., 2019 | Psoriasis | 1.4 per 100 PY | 
| P. C. van de Kerkhof et al., 2016 | Psoriasis (secukinumab 300 mg) | 1.4 per 100 SYs |

#### Fungal Infections

Candida infections emerged as a consistent safety signal across IL-17A antagonist therapy, with rates varying by agent and indication.

| Study | Indication | Treatment | Candida infection rate |
|-------|------------|-----------|----------------------|
| D. Saunte et al., 2017 | Psoriasis/PsA | Secukinumab | 1.7% |
| P. C. van de Kerkhof et al., 2016 | Psoriasis | Secukinumab 300 mg | 3.55 per 100 SYs |

### Hypersensitivity and Immunogenicity Outcomes

Injection site reactions occurred at low rates across studies.

| Study | Indication | Treatment | Injection site reaction rate |
|-------|------------|-----------|--------------------------|
| A. Deodhar et al., 2019 | Psoriasis | Secukinumab | 1.2 per 100 PY |

### Other Safety Outcomes

#### Cardiovascular Events

Major adverse cardiovascular events (MACE) remained low across indications.

| Study | Indication | Treatment | MACE rate |
|-------|------------|-----------|---------------------|
| P. Mease et al., 2015 | Psoriatic arthritis | Secukinumab | 0.6 per 100 PY |

## Synthesis

### Context and Population Distinctions

Safety outcomes with IL-17A antagonists showed clear patterns that varied by indication and patient population. Serious infection rates showed the inverse pattern of infection susceptibility in psoriatic arthritis patients compared to ankylosing spondylitis.

### Mechanistic Explanations

The pattern of predominantly mucocutaneous Candida infections with IL-17A antagonists has a clear mechanistic basis due to the role of IL-17A in immunological protection against Candida species. The low rate of opportunistic infections indicates that IL-17A antagonism does not radically compromise the immune system.

### References

[1] D. Saunte et al. (2017). Candida infections in patients treated with interleukin‐17 inhibitors and their practical management. British Journal of Dermatology.  
[2] Q. Gao et al. (2021). Efficacy and safety of IL-17 inhibitors for patients with psoriatic arthritis: a systematic review and meta-analysis. European Review for Medical and Pharmacological Sciences.