Elicit: IL-17A Antagonism: Safety and Immunologic Impacts

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 and OpenAlex.

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.