Clinical bottom line
Biologic therapies targeting interleukin-5 (IL-5) pathways have become integral in managing eosinophilic airway diseases such as eosinophilic nasal polyposis (ENP) and severe asthma. While these agents offer significant clinical benefits, allergic reactions—including hypersensitivity and anaphylaxis—remain important concerns requiring vigilant diagnosis and management. Recent evidence highlights evolving strategies for early recognition, risk stratification, and tailored management of allergic reactions to anti-IL-5 biologics, underscoring the need for allergy clinicians to integrate updated protocols into practice to optimize patient safety and therapeutic outcomes.
What the evidence shows
Anti-IL-5 biologics, including mepolizumab, reslizumab, and benralizumab, target eosinophilic inflammation by inhibiting IL-5 or its receptor, thereby reducing eosinophil survival and activity. These agents have demonstrated efficacy in reducing nasal polyp size and improving symptoms in ENP, as well as decreasing exacerbations in severe eosinophilic asthma (Elwany et al., 2026). However, allergic reactions to these biologics, though infrequent, can range from mild infusion-related reactions to severe anaphylaxis.
Elwany et al. (2026) provide a comprehensive overview of allergic reactions associated with anti-IL-5 therapies in ENP, noting that hypersensitivity reactions may be under-recognized due to overlapping symptoms with disease exacerbations. The authors emphasize that skin testing and in vitro assays can aid in confirming IgE-mediated hypersensitivity, although standardized protocols remain lacking. Premedication strategies and slow infusion rates have been proposed to mitigate reaction risks, but evidence is largely from observational data and expert consensus.
The immunogenicity of anti-IL-5 agents varies, with benralizumab showing lower rates of anti-drug antibody formation compared to mepolizumab and reslizumab, potentially correlating with fewer allergic events (Elwany et al., 2026). Nonetheless, delayed hypersensitivity reactions have been reported, necessitating prolonged vigilance beyond initial dosing.
Management guidelines for allergic reactions to biologics targeting other cytokines (e.g., TNF-α, IL-1) emphasize the importance of multidisciplinary collaboration, desensitization protocols, and alternative therapy consideration when reactions occur (Taylor et al., 2007). While direct data on IL-5 biologics are limited, these principles are applicable and warrant adaptation for eosinophilic disease contexts.
Caveats and uncertainty
Current evidence on allergic reactions to IL-5 pathway biologics is limited by small sample sizes, heterogeneity in reaction definitions, and a paucity of randomized controlled trials specifically addressing hypersensitivity management. Most data derive from case series, registries, or extrapolation from other biologic classes, which may not fully capture the unique immunologic profiles of IL-5 inhibitors.
Diagnostic tools such as skin testing and serum assays lack standardized sensitivity and specificity metrics for these agents, limiting their routine clinical utility. The role of premedication and infusion modifications remains based on expert opinion rather than robust comparative trials.
Furthermore, the long-term immunogenicity and risk of delayed hypersensitivity reactions require ongoing surveillance, as current follow-up durations in pivotal trials are relatively short. Patient-specific factors influencing reaction risk, such as atopy or prior biologic exposure, are incompletely characterized.
How this may change practice
Allergy clinicians should maintain a high index of suspicion for allergic reactions in patients receiving anti-IL-5 biologics, particularly when new or worsening symptoms arise shortly after administration. Incorporating detailed clinical assessment protocols and considering referral for allergy testing may improve diagnostic accuracy.
Premedication with antihistamines or corticosteroids and adjusting infusion rates could be considered in patients with prior mild reactions, although these strategies should be individualized. In cases of confirmed IgE-mediated hypersensitivity, desensitization protocols adapted from other biologic therapies may enable continued treatment, but require specialist oversight.
Clinicians should engage in multidisciplinary discussions with pulmonologists and otolaryngologists to balance the benefits of IL-5 biologics against allergic reaction risks, especially in patients with limited alternative options. Documentation and reporting of allergic events will enhance pharmacovigilance and inform future guideline development.
Overall, awareness and proactive management of allergic reactions to IL-5 pathway biologics can optimize patient safety and therapeutic success in eosinophilic airway diseases.