Clinical bottom line
Novel anti-IL-17 therapies represent a promising but still investigational approach for managing severe neutrophilic asthma, a phenotype often refractory to conventional treatments including corticosteroids and anti-IL-5 biologics. Emerging evidence suggests IL-17 plays a key role in neutrophilic airway inflammation and steroid resistance, making IL-17 blockade a rational therapeutic target. However, clinical data on efficacy and safety remain limited, and patient selection criteria are not yet well defined. Anti-IL-17 agents warrant further rigorous evaluation in well-designed clinical trials before routine clinical adoption.
What the evidence shows
Severe neutrophilic asthma is characterized by airway inflammation dominated by neutrophils rather than eosinophils, often associated with poor response to corticosteroids and standard biologics targeting IL-5 pathways (Syabbalo et al., 2022). IL-17, a pro-inflammatory cytokine produced by Th17 cells, has been implicated in promoting neutrophilic inflammation and airway remodeling in asthma (Nightingale Syabbalo et al., 2020). This cytokine axis contributes to steroid resistance and persistent airway inflammation, highlighting IL-17 as a putative therapeutic target.
Preclinical and early clinical studies have demonstrated that IL-17 blockade can reduce neutrophilic inflammation and improve airway hyperresponsiveness in experimental models (Syabbalo et al., 2022). However, clinical trials specifically targeting IL-17 in severe neutrophilic asthma remain scarce. Existing biologics approved for severe eosinophilic asthma, such as anti-IL-5/IL-5R agents, show limited efficacy in neutrophilic phenotypes, underscoring the unmet need for alternative approaches (Dhariwal et al., 2020; 2021).
Current evidence from observational cohorts and mechanistic studies suggests that IL-17 inhibition may reduce exacerbation frequency and improve lung function in selected patients with neutrophilic asthma, but these findings are preliminary and derived from small sample sizes or extrapolated from related inflammatory diseases (Syabbalo et al., 2022; Nightingale Syabbalo et al., 2020). The heterogeneity of neutrophilic asthma and overlap with fungal sensitization or other comorbidities complicate interpretation of response to biologics (Dhariwal et al., 2020).
Caveats and uncertainty
The clinical development of anti-IL-17 therapies in severe neutrophilic asthma is in early stages, with a paucity of large randomized controlled trials directly assessing efficacy and safety. The heterogeneity of asthma phenotypes and lack of standardized biomarkers for neutrophilic inflammation challenge patient selection and trial design. Moreover, IL-17 plays complex roles in host defense and immune regulation, raising concerns about potential adverse effects such as increased susceptibility to infections.
Existing biologics targeting other pathways (e.g., IL-5) have established failure criteria and response predictors, but analogous frameworks for anti-IL-17 agents are lacking (Dhariwal et al., 2021). The overlap of neutrophilic asthma with fungal sensitization or other inflammatory endotypes further complicates treatment stratification. Long-term safety data and head-to-head comparisons with current standard-of-care biologics are not yet available.
How this may change practice
If ongoing and future trials confirm efficacy and safety, anti-IL-17 therapies could fill a critical gap in managing severe neutrophilic asthma patients who do not respond adequately to corticosteroids or anti-IL-5 biologics. Incorporation of IL-17 pathway inhibitors may enable more precise, phenotype-driven treatment strategies, improving symptom control and reducing exacerbations in this difficult-to-treat subgroup.
Clinicians should remain aware of the evolving evidence base and consider participation in clinical trials evaluating anti-IL-17 agents. Biomarker development to identify patients with IL-17–driven inflammation will be essential to optimize therapeutic targeting. Until robust clinical data emerge, anti-IL-17 therapies should be regarded as investigational and not yet part of routine management.