International Journal of Pediatric Otorhinolaryngology 127 (2019) 109674

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International Journal of Pediatric Otorhinolaryngology

journal homepage: www.elsevier.com/locate/ijporl

Review Article

Anti-IgE treatment in allergic rhinitis T

a,∗ b c
Nuray Bayar Muluk , Sameer Ali Bafaqeeh , Cemal Cingi
a
Kirikkale University, Medical Faculty, Department of Otorhinolaryngology, Kirikkale, Turkey
b
King Saud University, Faculty of Medicine, Department of Otorhinolaryngology, Riyadh, Saudi Arabia
c
Eskisehir Osmangazi University, Medical Faculty, Department of Otorhinolaryngology, Eskisehir, Turkey

A R T I C LE I N FO A B S T R A C T

Keywords: Objectives: To review the efficacy of anti-IgE therapy in allergic rhinitis (AR).
Allergic rhinitis Methods: Literature search was performed using the PubMed and Proquest Central databases at Kırıkkale
Seasonal allergic rhinitis University Library.
Perennial allergic rhinitis Results: Although the skin prick testing in patients suffering from AR is positive (indicating that antigen-specific
Anti-IgE treatment
Immunoglobulin E has been produced), there is no association with overall circulating IgE levels. Correlation
Omalizumab
was lacking between circulating IgE level and either skin prick tests or laboratory testing for specific IgE.
Omalizumab binds to uncomplexed IgE in man more avidly than does Fc-epsilon. The effect of omalizumab is to
lower the level of IgE and downgrade production of FceRI receptors (which bind IgE) in mast cells and basophils,
causing less mast cell recruitment and responsivity and thus diminishing eosinophilic infiltration and activation.
Anti-IgE therapy through omalizumab may shorten the lifetime of mast cells and causes dendritic cells to
downgrade their production of FcεRI. There are reports indicating benefit from omalizumab in managing food
allergies, nasal polyp formation, essential anaphylaxis, AR, venom allergy and eczema. Omalizumab acts to
lessen circulating IgE levels, whilst reducing production of FceRI by mast cells and basophils. The fact that
omalizumab influences how eosinophils respond may be down to disruption of the antigen-IgE-mast cell in-
teractions, with mast cells being recruited at lower levels and thus chemotactic eosinophilic recruitment via
cytokines being greatly reduced. Omalizumab has the effect in cases of perennial AR of blocking the increased
eosinophilic recruitment and tissue infiltration initiated by seasonal antigens. Likewise, in omalizumab-treated
cases, circulating unbound IgE levels showed significant decreases. For patients with perennial AR, the average
daily nasal severity score was significantly reduced where omalizumab was administered, compared to placebo.
Conclusion: Omalizumab has efficacy in ameliorating symptoms and reduces the necessity for additional med-
ication in both seasonal and perennial allergic rhinitis

1. Introduction
Given the centrality of IgE within multiple allergic disorders, it
might be anticipated that omalizumab show benefit for the treatment of
allergic disorders [1]. Indeed, benefit from omalizumab has been shown
in treating food allergy, nasal polyp formation, essential anaphylaxis,
AR, venom allergy and eczema [1]. Various researchers have in-
vestigated using omalizumab and comparable anti-IgE im-
munoglobulins to treat food allergy, nasal polyposis, bullous pemphi-
goid, asthma associated with eosinophilic granulomatosis with
polyangiitis (Churg-Strauss), and allergic bronchopulmonary aspergil-
losis [2–8].
The use of omalizumab either before or at the same time as im-
munotherapy given by subcutaneous injection, has been reported on
several occasions. The rationale for using omalizumab was to dampen
systemic allergic responses to immunotherapy administered for inhaled
allergen or Hymenoptera sting allergies [9,10]. Immunotherapy on its
own has less efficacy in reducing symptoms in AR than when used in
combination with omalizumab [11]. Other applications of omalizumab
include educing patients' systemic allergic responses when undergoing
rapid desensitisation [11] +/− enhancing the benefits derived from
immunotherapy [12].
Omalizumab has efficacy in diminishing the symptomatic burden
and use of palliative medication in both SAR (seasonal AR) and PAR
(perennial AR) [13–17].

∗
Corresponding author. Birlik Mahallesi, Zirvekent 2. Etap Sitesi, C-3 blok, No: 6-3/43, 06610, Çankaya, Ankara, Turkey.
E-mail addresses: nuray.bayar@yahoo.com (N. Bayar Muluk), bafaqeeh@hotmail.com (S.A. Bafaqeeh), ccingi@gmail.com (C. Cingi).

https://doi.org/10.1016/j.ijporl.2019.109674
Received 20 May 2019; Received in revised form 8 August 2019; Accepted 5 September 2019
Available online 10 September 2019
0165-5876/ © 2019 Elsevier B.V. All rights reserved.
N. Bayar Muluk, et al.
2. Methods
Literature search was performed using the PubMed and Proquest
Central databases at Kırıkkale University Library from 2018 to 1980
years. Key words of allergic rhinitis (AR), seasonal allergic rhinitis
(SAR), perennial allergic rhinitis (PAR) and/or anti-IgE treatment were
used. Randomized controlled trials (RCT), placebo-controlled trials,
controlled-trials (there were 34 trials in the first, second and third
groups), retrospective studies, reviews, book chapters, cross-sectional
studies, experimental studies and congress presentations were all in-
cluded.
3. Total IgE levels and allergic disease
The usual normal reference range in adults and older teenagers for
serum IgE is up to 100 IU/mL. Total IgE may be raised in a variety of
conditions, such as allergic disorders, primary immunodeficiency syn-
dromes, infective episodes (viruses or parasites), specific inflammatory
disorders and particular malignant neoplasms [18]. A raised total cir-
culating IgE does not, therefore, point to any one allergic disorder. Here
we are concerned with allergic disorders, leaving IgE's role in serology
in general to be addressed elsewhere [18].
3.1. Raised total circulating IgE
It is common for cases of allergic disease to have a raised circulating
IgE level. Nonetheless, both a threshold for diagnosing allergic disease
and a discriminator between particular disorders are lacking [19,20],
meaning that it is seldom possible to diagnose allergic disorders on the
basis of IgE level alone.
If the total IgE level exceeds 66 IU/mL, the risk of possessing in-
haled allergen-specific IgE immunoglobulins rises 37 times compared to
when the level is at the bottom of the reference range [21].
The mean value for IgE in school children is 51 IU/mL, but where
children have both allergic eczema and asthma, the mean value reaches
985 IU/mL. If asthma, allergic dermatitis or AR exist in isolation, the
expected mean values are 305, 273 and 171 IU/mL, respectively [22].
For the group with allergic disorders considered at all ages, eczema
results in the highest IgE titre, with allergic asthma, PAR and SAR re-
sulting in lower values [19]. A cutoff value of 100 IU/mL used to dif-
ferentiate between cases of allergy and normality, lead to 78% of
asthmatic cases and 60% of AR cases being correctly classified, but with
20% of cases incorrectly classified by this technique [23].
3.2. The ratio of allergen-specific IgE to total IgE
The term “specific activity” refers to the ratio of allergen-specific
IgE to total IgE [24]. The usefulness of this ratio has been researched in
diagnosing different allergic conditions and to anticipate how patients
will respond to treatment with omalizumab. One group reported that
specific activity conferred no additional diagnostic utility to the use of
allergen-specific IgE level on its own [25]. Nonetheless, where omali-
zumab was used in asthma, a diminished response to the treatment
correlated with a specific activity above 3–4% [26].
Eckl-Dorna et al. [27] investigated the efficacy of intranasal ad-
ministration of “major birch pollen allergen Bet v 1, omalizumab or
placebo” on the levels of “total and allergen-specific IgE” in patients
with birch pollen allergy. Bet v 1 intranasal challenge induced increase
of “Bet v 1-specific IgE levels” as 59.2% (median) which is significantly
different from other groups (P = 0.016). When challenge was per-
formed with omalizumab, there were no significant differences in al-
lergen-specific and total IgE levels. However, total IgE increased sig-
nificantly after treatment (before treatment, mean IgE: 131.83 kU/L
and after treatment, mean IgE: 505.23 kU/L) and IgE-omalizumab
complexes were also detected in subjects received subcutaneous oma-
lizumab. They concluded that intranasal allergen administration
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International Journal of Pediatric Otorhinolaryngology 127 (2019) 109674
increased allergen-specific IgE levels. Intranasal omalizumab adminis-
tration did not increase systemic total or allergen-specific IgE levels.
3.2.1. IgE levels in allergic rhinitis
Positive responses to skin prick testing have an association with AR,
but does not depend on the amount of total IgE [28]. Total IgE levels
are relatively insensitive to detect cases of symptomatic AR, only pin-
pointing 44% of such cases. PAR sufferers have IgE levels that do not
correspond to either positive skin prick test results or abnormal results
in laboratory-based IgE serology [29]. Furthermore, AR may co-exist
with an IgE level within the normal range [30]. To diagnose SAR or
PAR, there needs to be an appropriate history, physical findings and an
elevated titre for IgE specific to inhaled allergens [31].
4. Omalizumab
Omalizumab was discovered in the course of traditional cell hy-
bridisation in somatic cell lineages and is a monoclonal antibody [32].
An antibody of monoclonal type, MAE11, was found in mice, the an-
tigen-binding site of which targets the FcεRI receptor of basophils and
mast cells [33–35].
Omalizumab's clinical effects are due to a number of pharmacolo-
gical actions. The agent works by binding uncomplexed IgE more avidly
than the FcεRI molecule does [36–38]. There is no binding with the
FcεRI of basophils, which are the usual receptors for IgE. Part of the
molecule consists of human IgG1 immunogloblobulin portions. Neither
does it bind to IgE already adherent to FcεRI on basophils or the FcεRII,
which is located on other lineages (e.g. lymphocytes, monocytes, eo-
sinophils or thrombocytes) [38–43]. Furthermore, since omalizumab
cannot bind IgE that has complexed with FcεRII, there is lower cyto-
toxicity that occurs than would otherwise be the case for cells, such as
thrombocytes, that possess the receptor [38,44].
The level of circulating IgE is directly correlated with the level of
FcεRI expression by basophils, hence administering omalizumab leads
to lower FcεRI expression through its effect on circulating IgE [45–48].
Whilst IgE bound to basophils is unaffected by omalizumab, monomeric
IgE produced by plasma cells may be bound by the agent, since the
FcεRI binding site remains open in this case [48,49]. Given that FcεRI is
also produced by antigen-presenting cells and eosinophils, it is to be
expected that omalizumab will hinder attachment of IgE here, too, thus
modulating these cells' immune function [50]. It has been demonstrated
that dendritic cells express fewer FcεRI when omalizumab is given to
cases of SAR [51]. There are also reasons to believe that FcεRI and
FcεRII are expressed differentially on other cells of the immune system
as IgE levels vary [52–54].
4.1. Mechanisms of action
Omalizumab binds only IgE, not other immunoglobulins, such as
IgG or IgA. Significantly, omalizumab has no binding affinity for the
receptors of IgE or to IgE complexed to the α-portion of FcεRI, and in
this way it does not cause increased mast cell or basophil activity by
interaction with unfree IgE [55].
Effective therapy necessitates a profound diminution in unbound
IgE, since mast cells and basophils carry between 104 and 106 FcεRI
molecules, the majority of which IgE occupies. Indeed, occupation by
just 2000 IgE immunoglobulins results in 50% of the full histaminergic
response by basophils, so IgE levels need to be very low indeed to stop
mast cells or basophils from being stimulated [56].
Both the high and low affinity Fcε receptors located on the mem-
brane of basophils and mast cells decrease markedly in response to
omalizumab therapy, albeit the timing is not identical in both cases
[57–62].
Omalizumab works by reducing the circulating IgE level and
causing a decrease in FcεRI numbers on mast cells and basophils, which
leads to less likelihood of mast cells being activated and, in turn,
N. Bayar Muluk, et al.
Fig. 1. Mechanisms of action of omalizumab. Adapted from reference 44.
decreased eosinophilic recruitment and infiltration. Anti-IgE ther-
apeutic interventions like omalizumab, potentially shorten the lifespan
of mast cells and decreases FcεRI numbers on dendritic cells (see Fig. 1)
[44].
Omalizumab plays a key part in preventing allergic inflammatory
responses. At present, the evidence suggests the agent can both sig-
nificantly reduce the underlying inflammatory heightening and stop
flare-ups occasioned by the patient coming into contact with allergenic
substances. Bearing in mind the spectrum of actions achieved by anti-
IgE activity on basophils, mast cells, eosinophils and dendritic cells, we
may conclude that the pharmacological actions go beyond simply in-
hibiting the response via IgE mechanisms and in fact may also control
T-cells that respond to allergen. Thus, omalizumab has a unique mode
of action that encompasses preventing hypersensitivty and inhibiting
both chronic and acute aspects of the inflammatory response in allergy
[44].
The fact that IgE serology shows marked diminution in IgE titres in
children who have received omalizumab points to the reduction in
unbound IgE as a key element in achieving a therapeutic response
[63,64]. Fractional exhaled nitrogen oxide levels drop when children
are administered omalizumab, even when inhaled corticosteroids are
markedly reduced [65] and lower IgE levels correlate both with fewer
basophils in peripheral blood and a better clinical result [66].
5. Anti-IgE therapy in allergic rhinitis
Omalizumab both lowers serological titres of free IgE and causes
mast cells and basophils to produce fewer FcεRI receptors. For SAR
cases, the agent damps down the periodic increases in eosinophilic
activation and infiltration that occur when allergen levels rise season-
ally. Since FcεRI numbers on dendritic cells in the systemic circulation
also fall in response to omalizumab, there may be an effect on Th2
recruitment and division, with reduced antigen presentation occurring.
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International Journal of Pediatric Otorhinolaryngology 127 (2019) 109674
Omalizumab has been shown to produce clinical benefit in moderate
and severe allergic asthma sufferers, those with SAR or PAR, and those
who have both conditions together. It achieves this through systemic
anti-IgE activity. The way omalizumab exerts such widespread anti-
inflammatory activity across multiple systems and the demonstrable
clinical improvements seen in both allergic asthma and AR highlight
the central role that IgE plays in such allergic disorders [44].
In pediatric patients, current indications for treatment with omali-
zumab are mainly “moderate-to-severe uncontrolled allergic asthma
and chronic spontaneous urticaria (CSU)” [67]. Addition to these ap-
proved applications, omalizumab treatment has been explored in other
“allergic and non-allergic diseases” [68,69]. Recent data suggested that
omalizumab is clinically effective and generally well tolerated in chil-
dren and its possible use for other IgE-mediated disorders, for example
allergic rhinitis, food allergy, and anaphylaxis is also suggested [67]. As
FDA has approved omalizumab for children aged 12 years and over, the
studies related omalizumab in pediatric patients were set the lower age
limit for administration of omalizumab at 12 years [68,69].
There are two placebo-controlled studies for the efficacy of omali-
zumab in allergic rhinitis. In Rolinck-Werninghaus et al.'s [70] placebo-
controlled study, birch and grass pollen allergic patients with seasonal
allergic rhinitis (SAR) (aged 6–17 years), group A (n = 53) received
placebo and group B (n = 54) received Omalizumab (anti-IgE) treat-
ment before and during the grass pollen season. They reported that the
symptom load in SAR patients with Omalizumab (anti-IgE) correlates
with free total IgE levels.
In another study of Rolinck-Werninghaus et al. [71], of 221 subjects
with birch and grass pollen allergic rhinoconjunctivitis (aged from 6 to
17) were included. Group A were given) specific immunotherapy (SIT)-
birch + placebo and group B received anti-IgE (Omalizumab) therapy,
group C received SIT grass pollen monotherapy and group D received
combined treatment of SIT and Omalizumab.They reported that” co-
seasonal Omalizumab therapy” showed considerable effects in children
N. Bayar Muluk, et al.
with SAR. The combination of “SIT and Omalizumab” was clinically
superior to each treatment alone for the following 1st year.
Research involving patients whose AR was triggered by ragweed
allergy showed that FcεRI on basophils decreased 73% following 7 days
of omalizumab treatment, with a concomitant reduction in allergic
hypersensitivity reactions to nasal inhalation of the allergen [72].
A different study, which involved AR sufferers allergic to dust mites
and used i.v. omalizumab found that FcεRI numbers did not alter fol-
lowing 7 day therapy, but did decrease by 90% after 70 days [59].
When mast cell numbers were counted by staining for tryptase, they
were found to be unchanged, but fewer receptors were being manu-
factured by the cells. Changes in mast cell functioning went along with
a slowly progressive decrease in the response to skin prick tests [52,59].
At the two week mark, late-phase skin reactions had diminished, whilst
at the eight week mark, the early-phase response was similarly muted
[52,53].
A study into eosinophilic-type allergic reactions looked into using
omalizumab in 30 cases of SAR [73]. Serological measures of unbound
IgE showed a significant decrease in the group treated with omali-
zumab, compared with no change in the placebo recipients
(p = 0.0001). Circulating eosinophil numbers rose significantly in
placebo recipients, but not in omalizumab recipients, a difference that
was statistically significant (p = 0.04). Nose biopsy specimens were
stained to demonstrate eosinophil peroxidase and thus eosinophil
numbers. The profile obtained matched the expected rise in numbers
seasonally and the dampening effect obtained through treatment. In
addition, circulating IgE levels and eosinophil numbers were correlated.
SAR seems to involve a spike in inflammatory activity induced by the
allergen and such spikes may be amenable to modification by omali-
zumab [73].
A different research effort demonstrated a reduction (compared to
placebo) in plasmacytoid dendritic cells (pDC1) in 49 paediatric cases
of SAR who were given both omalizumab and specific immunotherapy
concurrently. These reduced numbers were observed when grass pollen
levels rose, but not when birch pollen was high, despite the cases
having a response to both allergens. Whilst firm conclusions are hard to
reach from such a result, the data lend weight to the hypothesis that
omalizumab modulates the behaviour of dendritic cells at the point in
their lifecycle where they have yet to migrate into tissues and com-
pletely mature [44].
In mild allergic asthma [74], omalizumab creates important
changes in the level of eosinophilic infiltration of the airways and other
structures, as also in seasonally-influenced flare-ups in SAR [73]. How
omalizumab affects eosinophils may, in part, be down to interference
with IgE's ability to bind allergen and activate mast cells. If mast cells
are not activated, cytokine release does not occur and thus eosinophils
are not attracted chemotactically. Mast cells secrete a range of cyto-
kines, which act on both short term and long term inflammatory pro-
cesses. Thus, it is conceivable that omalizumab prevents not merely the
acute allergic response, but also longer term immune adaptation to
allergens, such as activation of particular immune cell types, changes in
tissue architecture and alterations in the function of the airways.
Confirmation that IgE plays a greater role than in just mediating the
acute phase of an allergic reaction comes from the pharmacology of
omalizumab, which is effective in both moderately severe and severe
asthma, and allows the dose of inhaled steroids to be reduced, whilst
also making flare ups less frequent [63,75–79].
In this respect, that omalizumab acts to downgrade FcεRI produc-
tion [80–82] and reduce creation of new dendritic cells [80] is of
especial importance. Omalizumab changes the way allergens are pre-
sented, the key step in the development of allergic hypersensitivity.
Altering this step appears to offer an unparalleled development in
therapy for asthma and allergic disorders of other kinds [44].
Omalizumab dampens the intranasal response to allergens. In a
study by Hanf et al. [83], 23 AR (both SAR and PAR) sufferers were
randomly allocated to receive either placebo or subcutaneous
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International Journal of Pediatric Otorhinolaryngology 127 (2019) 109674
omalizumab (at a minimum dose of 0.016 mg/kg per IU of IgE/mL
every 4 weeks) for a period of 16 weeks. After the 16 weeks, intranasal
allergen challenge resulted in symptoms of less severity in cases which
had received omalizumab than either those who got placebo or before
the intervention was undertaken. Nasal lavage specimens were ana-
lysed for albumin and TNF-alpha. Both parameters were reduced in
comparison with baseline values, leading to the conclusion that in-
flammation within the nose had decreased [35].
According to Tsabouri and colleagues [84], there are statistically
significant improvements in symptoms, the need for rescue drugs, and
life quality when omalizumab is used by patients with allergic rhino-
sinusitis that has not fully responded to previous treatment. The study
was a meta-analysis and found that omalizumab was associated with
lower use of other allergic pharmacological treatments and improved
DNSSS (daily nasal symptom severity score) in comparison with pla-
cebo, in rhinoconjunctivitis, both perennial and seasonal subtypes. Al-
though the evidence was incomplete, there were indications from
randomised trial data that quality of life was also better. From the point
of view of safety, the agent appears well-tolerated and with a favour-
able adverse events profile, albeit the evidence to date cannot show
infrequent adverse events.
The meta-analysis of RCTs [85] and a systematic review and meta-
analysis of RCTs for the use of omalizumab [84] for the treatment of AR
suggested that omalizumab can effectively and safely reduce symptoms
scores of patients with AR. However, concerns for cost of therapy and
uncertainty around optimal positioning have presented limitations in
licensing omalizumab for patients.
Anti-IgE works to dampen immune allergic reactions by lowering
unbound IgE levels to around 10IU/mL within a period of hours [86],
leading to additional benefit when used alongside specific im-
munotherapy (SIT), and indeed lowering the incidence of acute allergic
responses during treatment with SIT [84].
There have been large scale phase III clinical trials to establish that
omalizumab is effective in symptomatic relief and gives better life
quality in cases of SAR and PAR [17,86–88].
Belliveau et al. [35] reported that omalizumab has been well tol-
erated for uncontrolled moderate to severe allergic asthma and allergic
rhinitis in children, adults, and adolescents for 52-week duration.
However in treated patients, malign neoplasms have been observed
which were likely not related to omalizumab therapy. To confirm the
safety, cost-effectiveness and duration of treatment, further multi-
centric controlled prospective studies are required.
5.1. Seasonal allergic rhinitis
The first reports to mention using omalizumab in SAR are RCTs
featuring placebo and double-blinding conducted on older children and
adults with ragweed hypersensitivity and aiming to establish a dose
range [14,17]. The first RCT revealed no significant difference in
symptom score (the main outcome measure) between placebo and
omalizumab. Possible reasons for this included: less marked seasonality
in flare-ups, varied reporting of symptoms and an inadequate numbers
of cases in which specific IgE levels fell the requisite amount [14].
Plewako and colleagues [73] looked at 30 cases of SAR, rando-
mising the intervention to either placebo or omalizumab. The inter-
vention either preceded the birch pollen season or coincided with its
onset and continued for the whole season to a maximum duration of six
weeks. Blood and nose biopsy specimens were used to gauge eosinophil
levels (using eosinophil peroxidase and eosinophil granule proteins,
which are specific to eosinophils). Omalizumab resulted in a significant
reduction in eosinophil activity in comparison with placebo. There was
a correlation between eosinophil levels and serum unbound IgE.
There has also been a trial of omalizumab in cases of SAR of mod-
erate to severe level, triggered by birch pollen [13]. 251 cases received
either placebo or subcutaneous omalizumab. Twice as many cases re-
ceived active agent as received placebo. The dose was 300 mg once per
N. Bayar Muluk, et al.
three weeks for three times, or two doses with a 4 week interval, as
dictated by the pretreatment IgE serology. The results obtained com-
pared favourably with those in the ragweed trials. A substudy looked at
30 cases and determined that omalizumab lowered circulating and in-
tranasal eosinophil levels. The unbound circulating IgE titre had a
statistically significant positive correlation with circulating eosinophils,
eosinophils identified in biopsy specimens and numbers of cells ex-
pressing FcεRI receptors in biopsies. Furthermore, the severity of
symptoms as revealed by nasal, ocular and combined scores, correlated
positively to a significant degree with a marker specific to eosinophils
that had become activated [35,73].
5.2. Perennial allergic rhinitis
The earliest report on using omalizumab in PAR is for an RCT fea-
turing placebo and double-blinding conducted on 289 cases with
moderate to severe illness that had lasted for two years, who had po-
sitive skin prick testing to frequently encountered perennial allergens
(dust mite, canine or feline antigens) and whose IgE serology had a
level of 30–700 IU/mL. The intervention was either omalizumab or
placebo, both given subcutaneously and for 16 weeks [88]. The inter-
vention occurred one or two times each month to achieve a dosage
exceeding 0.016 mg/kg omalizumab per IU of IgE/mL every 4 weeks. At
the 4 week mark, the daily score for nasal symptoms was significantly
improved in omalizumab cases compared to placebo cases. The cases
which had not responded to immunotherapy or nasal steroids were
analysed post hoc, with the finding that these subgroups had also im-
proved at a statistically significant level. Taking omalizumab resulted in
lower levels of rescue medication use daily and fewer days monthly on
which such medication was needed. The omalizumab recipients had
improved RQoL scores in all domains, that were of clinical significance
and the rate at which symptoms were considered “under complete
control” or “markedly improved” went up (53% vs 34%, p = 0.001)
[35].
6. Conclusion
Omalizumab can bind specific IgE in its unbound state with greater
avidity than occurs when IgE binds Fcε. Omalizumab diminishes cir-
culating unbound IgE and lowers the level of FcεRI expressed by mast
cells and basophils, thus leading to fewer activated mast cells and lower
sensitivity, less infiltration by eosinophils and lower levels of eosino-
philic activation. Omalizumab may also shorten mast cell lifetimes.
Dendritic cells express fewer FcεRI molecules in omalizumab-treated
individuals. The agent can both diminish the severity of symptoms and
lessen the necessity for other pharmacological interventions in SAR and
PAR.
Authors' contributions and responsibilities
Nuray Bayar Muluk: Planning, literature survey, writing of the
manuscript; Sameer Ali Bafaqeeh: Planning, literature survey; Cemal
Cingi: Planning, literature survey, English correction
Conflicts of interest
Author Nuray Bayar Muluk declares that she has no conflict of
interest.
Author Sameer Ali Bafaqeeh declares that he has no conflict of
interest.
Author Cemal Cingi declares that he has no conflict of interest.
Ethical approval
There is no need to obtain ethical approval, because this paper is a
review
5
International Journal of Pediatric Otorhinolaryngology 127 (2019) 109674
Informed consent
There is no need to take informed consent, because this paper is a
review.
Acknowledgement
With the exception of the data collection, the preparation of this
paper, including design and planning, was supported by the Continuous
Education and Scientific Research Association.
Support was scientific rather than financial.
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