Five
biological drugs are currently marketed for treatment of uncontrolled severe
asthma. They all block type 2 inflammatory pathways by targeting
IgE (
omalizumab), the
IL-5 pathway (
mepolizumab,
reslizumab,
benralizumab), or the IL-4/
IL-13 pathway (
dupilumab).
Hypereosinophilia has been observed in 4%-25% of patients treated with
dupilumab and is transient in most cases, although there have been reports of persistent cases of symptomatic
hypereosinophilia consistent with
eosinophilic granulomatosis with polyangiitis (EGPA),
eosinophilic pneumonia, eosinophilic
vasculitis, and sudden worsening of
asthma symptoms. Cases of EGPA have been reported with all biologics, including anti-IL-5 agents, and with
leukotriene receptor antagonists in publications or in the EudraVigilance database. In many cases, EGPA appears during tapering of systemic
corticosteroids or after switching from an anti-IL-5
biologic to
dupilumab, suggesting that systemic
corticosteroids or the anti-IL-5 agent were masking
vasculitis. This review investigates plausible mechanisms of
dupilumab-induced
hypereosinophilia and review cases of symptomatic
hypereosinophilia associated with
dupilumab. Blockade of the IL-4/
IL-13 pathway reduces eosinophil migration and accumulation of blood by inhibiting
eotaxin-3,
VCAM-1, and TARC without simultaneously inhibiting eosinophilopoiesis in bone marrow. When choosing the optimal
biologic, it seems necessary to consider the presence of
hypereosinophilia (>1500/μL), in which case an anti-IL-5/IL-5R agent is preferable. Furthermore, when switching from an anti-IL-5/5R to an anti-IL-4/13R agent, blood eosinophils and clinical progress should be closely monitored. Nevertheless, dual
therapy with anti-IL-5/5R and anti-
IL4/IL-13R agents may be needed for optimal control, since both the
IL-5 and the IL-4/
IL-13 pathways can simultaneously contribute to airway
inflammation. This approach can prevent the development of EGPA and other types of symptomatic
hypereosinophilia while maintaining control of nasal polyposis. In the near future, it will be possible to use a new generation of
biological therapies for the treatment of severe
asthma. These act at a higher level of the inflammatory cascade, as is the case of the antialarmins
tezepelumab and
itepekimab.