Elicit: IL-17A Antagonism: Safety and Immunologic Impacts
Safety and Immunologic Impacts of IL-17A Antagonism
IL-17A Antagonists Safety Profile
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 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. Hypersensitivity reactions were uncommon, with injection site reactions rates between 0.6 to 1.6 per 100 patient-years for secukinumab.
Long-term studies, including pooled analyses with over 12,000 patients, showed no increase in serious adverse events or infections over time, supporting the long-term safety of IL-17A antagonism across inflammatory conditions.
Methods
We analyzed 10 sources from an initial pool of 200, using various screening criteria focused on IL-17A antagonist intervention and safety outcomes.
Records from Elicit Search
- Total Found: 200
- Screened In: 10
- Screened Out: 190
Characteristics of Included Studies
| Author | 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 |
| Yufeng Yin et al., 2020 | Systematic review and meta-analysis | Ankylosing spondylitis | Secukinumab, ixekizumab | 1,733 patients | Week 16 |
| A. Deodhar et al., 2019 | Pooled clinical trials + post-marketing | Psoriasis, PSO, AS | Secukinumab 75, 150, 300 mg | 7,355 patients | Up to 5 years |
...
Infection Outcomes
Overall Infection Rates
| Study | Indication | Overall Infections | Serious Infections | Upper Respiratory Tract Infections |
|---|---|---|---|---|
| A. Deodhar et al., 2019 | Psoriasis | Not specified | 1.4 per 100 PY | Most common infection type |
| A. Gottlieb et al., 2022 | Psoriatic arthritis | Not specified | 1.8 per 100 PY | 3.5 per 100 PY |
Fungal Infections
| Study | Indication | Treatment | Candida Infection Rate | Notes |
|---|---|---|---|---|
| D. Saunte et al., 2017 | Psoriasis/PsA | Brodalumab | 4.0% | Slightly increased incidence |
| P. C. van de Kerkhof et al., 2016 | Psoriasis | Secukinumab 300 mg | 3.55 per 100 SYs | Nonserious, mild/moderate |
Hypersensitivity Reactions
| Study | Indication | Treatment | Injection Site Reaction Rate |
|---|---|---|---|
| A. Deodhar et al., 2019 | Psoriasis | Secukinumab | 1.2 per 100 PY |
Other Safety Outcomes
Malignancy incidence remained low and stable across indications. Rates per 100 patient-years:
- Secukinumab 300 mg: 0.77
- Secukinumab 150 mg: 0.97
Synthesis
Context and Population Distinctions
Safety outcomes with IL-17A antagonists showed clear patterns that varied by indication and population. Serious infection rates were inversely related to baseline characteristics of the patient population. This highlights the nuanced understanding required when interpreting data related to safety outcomes.
Mechanistic Explanations
The pattern of predominantly mucocutaneous Candida infections has a mechanistic basis grounded in IL-17A's role in immunological defense. This is evidenced by the increased susceptibility to Candida in patients with genetic defects in IL-17-related immune responses, reinforcing the rationale for monitoring such infections in those undergoing treatment with IL-17A antagonists.
References
- D. Saunte, U. Mrowietz, L. Puig et al. (2017). Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors. British Journal of Dermatology.
- Q. Gao, Y.-X. Zhao 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.
- A. Deodhar et al. (2019). Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Arthritis Research & Therapy.