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.