PROS: BIOLOGICALS ARE SAFE AND EFFECTIVE IN TREATING ALLERGIC
DISEASES
- Omalizumab is an anti-IgE humanized IgG1 monoclonal antibody (mAb)
which forms complexes with soluble IgE, inhibiting binding to its
high-affinity IgE-receptor (FcεRI) on effector cells such as
basophils, eosinophils and mast cells1. The paucity
of IgE-mediated cross-linking of allergen reduces effector cell
activation and the subsequent release of immune mediators such as
histamine, responsible for driving the salient symptoms of atopic
disease. Moreover, through reducing serum-free IgE, omalizumab
downregulates FcεRI expression on mast cells, basophils and dendritic
cells and IgE-CD23 interactions on B-cells1, in turn
downregulating IgE synthesis and T helper 2 (Th2) cell
differentiation.
- Data from two phase III clinical trials demonstrates that omalizumab
reduces disease exacerbations by ~55% in severe
asthma patients4 and leads to significant
improvements in mean nasal polyp scores (NPS) and nasal congestion
scores (NCS) in CRSwNP patients compared to
placebo5. Moreover, omalizumab significantly
improves patient quality of life compared to conventional therapies in
severe asthma6, CRSwNP5 and
chronic spontaneous urticaria7 for which it is
authorized.
- Mepolizumab and reslizumab are humanized IgG1 and IgG4 mAbs
respectively which bind directly to IL-5, inhibiting the activation
and recruitment of eosinophils1. Benralizumab,
another humanized IgG1 mAb, targets the IL-5 pathway
through binding to the α subunit of the IL-5R, impeding IL-5 signal
transduction1. Moreover, benralizumab binds to
FcγRIIIa on natural killer cells through its Fc region, depleting
eosinophils through antibody-dependent cellular
cytotoxicity1.
- Anti-IL-5 biologics demonstrate the most efficacy against allergies
characterized by eosinophilia, such as severe eosinophilic asthma and
CRSwNP. Systematic reviews have demonstrated that mepolizumab,
reslizumab and benralizumab reduce asthma incidence rate ratios by
0.49, 0.46 and 0.53, respectively and report that mepolizumab and
benralizumab reduce required daily oral corticosteroid
dose6. Moreover, preliminary data from phase III
trials have reported that severe CRSwNP patients treated with
mepolizumab (SYNAPSE: NCT03085797) or benralizumab (OSTRO:
NCT03401229) as an add-on therapy demonstrate improvements in total
endoscopic NPS and sinonasal symptoms, supporting their regulatory
body approval for disease management in the future.
- Dupilumab is a human IL-4Rα blocking IgG4 mAb which inhibits the
sister cytokines IL-4/IL-13 through blockade of their shared receptor
subunit1. IL-4 plays a key role in T2 immunity by
promoting Th2 differentiation and IgE class-switching in B cells.
- Originally approved for the treatment of AD, dupilumab significantly
improved symptom scores including Eczema Area Severity Index and itch
Numeric Rating Scale scores during phase III
clinicals8. Dupilumab is also authorised for the
treatment of severe asthma1, 6 and severe
CRSwNP9.
- Therefore, T2-targeting biologicals have greatly improved treatment
efficacy compared to conventional therapies in asthma, CRSwNP, chronic
spontaneous urticaria and AD.
- Novel biologicals are in development at a rapid pace, including
epithelial and keratinocytes-derived mediators and cytokines such as
thymic stromal lymphopoietic, IL-31 and IL-33, and may provide further
improvements in the management of T2-mediated diseases in the future.