Systematic review evaluates anti-IL-5 and anti-IL-5Rα biologics for eosinophilic respiratory and systemic diseases

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Frontiers in Medicine Published April 16, 2026 Medically reviewed May 25, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider anti-IL-5/IL-5Rα biologics for eosinophilic respiratory/systemic diseases, noting unreported safety and efficacy specifics.

This systematic review assessed the efficacy of anti-IL-5 and anti-IL-5Rα biologics in a population of patients with eosinophilic respiratory and systemic diseases. The conditions evaluated included severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndromes. The review concluded that these interventions are associated with improved outcomes for these specific patient groups.

The source document did not report the sample size, specific study settings, or the comparators used against which the biologics were evaluated. Consequently, the magnitude of benefit relative to standard care or placebo remains undefined within this summary. Furthermore, no data regarding adverse events, serious adverse events, discontinuations, or overall tolerability were provided in the input evidence.

Key limitations of this evidence include the absence of reported sample sizes, follow-up durations, and specific safety profiles. The review notes that disease activity often depends on IL-5–driven eosinophil activation despite disease-specific IL-5–independent signals, suggesting that not all disease manifestations may respond to these targeted therapies. Practice relevance is framed around the potential for integrated multi-omics signatures and clinical biomarkers to guide patient stratification, therapy selection, and treatment sequencing toward precision medicine for these complex conditions.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

Interleukin-5 (IL-5) is central to eosinophil differentiation, survival, and activation. Subsequent studies confirmed IL-5 receptor expression and mapped downstream signaling, showing that IL-5 promotes not only survival but also trafficking and effector functions, including adhesion, degranulation, reactive oxygen species generation, mediator release (cytokines and cysteinyl leukotrienes), and extracellular trap formation. However, the roles of eosinophils vary across diseases and tissue compartments. Multi-omics analyses of blood and tissue eosinophils across transcriptomic, proteomic, and lipid-metabolic layers reveal disease- and site-specific molecular states. These data support two opposing classes of modulators that shape IL-5–driven programs: pro-inflammatory signals (IL-4/IL-13, IL-33, NOD2-mediated innate signaling, and IFN-γ) that drive inflammatory eosinophil changes and can cooperate in some settings, and counter-regulatory signals (IFN-α and all-trans retinoic acid [ATRA]) that restrain these changes. Such modulation may influence tissue retention, effector functions, and broader eosinophil activities, including antiviral and homeostatic roles. Clinical studies of anti-IL-5 and/or anti-IL-5Rα biologics in severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndromes, and other eosinophilic diseases have improved outcomes, underscoring that disease activity often depends on IL-5-driven eosinophil activation despite disease-specific IL-5–independent signals. In this review, we summarize IL-5 biology from mechanisms to therapy and discuss how integrated multi-omics signatures and clinical biomarkers may guide patient stratification, therapy selection, and treatment sequencing toward precision medicine for eosinophilic respiratory and systemic diseases.