10.14639/0392-100X-N2745
Introduction. Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated. Objective. To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability. Materials and methods. Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed. Results. BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety. Conclusions. BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease.
text/xml
1827-675X
2745
en
Alberto Macchi
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
beclomethasone dipropionate
A systematic review of randomised controlled trials on  topical nasal steroids
Text.Serial.Journal
https://www.actaitalica.it/
44
Reviews
2024-04-22
2023-09-06
2024-04-23
2024-04-23
71-75
1
Alberto Macchi
2024/04/22
10.14639/0392-100X-N2745
71
ENT Clinic ASST Settelaghi, Head and Neck Research Foresic Center, Insubria University, Varese, Italy. Corrisponding author - macchi.doc@gmail.com 
1827-675X
beclomethasone dipropionate
en
75
A systematic review of randomised controlled trials on  topical nasal steroids
https://www.actaitalica.it/article/download/2745/1084
44
ACTA OTORHINOLARYNGOLOGICA ITALICA 2024;44:71-75; doi: 10.14639/0392-100X-N2745




Review


A systematic review of randomised controlled trials on
topical nasal steroids
Chiara Zeroli1, Armela Gorica1, Giulia Monti1, Paolo Giocondo Maria Castelnuovo1, Maurizio Bignami2, Alberto Macchi1
1
  ENT Clinic ASST Settelaghi, Head and Neck Research Foresic Center, Insubria University, Varese, Italy; 2 ENT Clinic ASST Lariana,
University of Insubria, Como, Italy


SUMMARY
Introduction. Intranasal corticosteroids (INCs) are the first line of therapy for chronic
sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most fre-
quently used is beclomethasone dipropionate (BDP). Over the years many studies have
evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and aller-
gic rhinitis (AR) along with nasal washes, which seems to be very well tolerated.
Objective. To analyse the data in the literature regarding the various therapeutic regimens
of BDP in different sinonasal disease and their efficacy and tolerability.
Materials and methods. Using different search engines, the posology, efficacy, and toler-
ability of BDP were reviewed and a total of 64 full-length articles were examined for eligi-
bility. After applying inclusion and exclusion criteria, 4 articles were reviewed.
Results. BDP is among the group of INCs with significant improvement of nasal symptoms
and has good efficacy and safety.
Conclusions. BDP nasal spray is one of the most frequently prescribed INC for rhinitis
and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful
improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and
the safety profile is similar to that of placebo in most patients. These results, in conjunction
with the significant benefit reported in subjects with CRS and AR, provide convincing evi-
dence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal
disease.
KEY WORDS: topical nasal steroids, chronic rhinosinusitis, rhinitis, allergic rhinitis,
beclomethasone dipropionate


                                                                                                   Received: September 6, 2023
Introduction                                                                                       Accepted: December 23, 2023

Allergic rhinitis (AR) is a common chronic inflammatory disease, and its                           Correspondence
prevalence is increasing worldwide in both adults and children 1. The most                         Alberto Macchi
common symptoms are sneezing, nasal itch, rhinorrhea, nasal obstruction,                           E-mail: Macchi.doc@gmail.com
and allergic conjunctivitis. There are different types of rhinitis: allergic, non-
allergic, mixed, or episodic. The most appropriate treatment for rhinitis is                         How to cite this article: Zeroli C, Gorica A,
                                                                                                     Monti G, et al. A systematic review of ran-
determined by multiple factors such as the most prominent symptoms, se-                              domised controlled trials on topical nasal ster-
verity, and age of the patient 2. If left untreated, AR along with rhinosinusi-                      oids. Acta Otorhinolaryngol Ital 2024;44:71-
tis may significantly affect the quality of life due to severe sleep disorders,                      75. https://doi.org/10.14639/0392-100X-N2745
fatigue, impaired memory and in some cases depression. There are many
                                                                                                   © Società Italiana di Otorinolaringoiatria
therapies used to treat AR and rhinosinusitis that focus on reducing airway                        e Chirurgia Cervico-Facciale
inflammation and improving symptom control, ranging from simple nasal
washes to steroids.                                                                                               OPEN ACCESS

Under current guidelines, intranasal corticosteroids (INCs) are considered the                     This is an open access article distributed in accordance with
                                                                                                   the CC-BY-NC-ND (Creative Commons Attribution-Non-
most effective drugs, and are recommended as first-line therapy. Numerous                          Commercial-NoDerivatives 4.0 International) license. The
studies have shown their effectiveness in treating allergic/non-allergic rhinitis,                 article can be used by giving appropriate credit and mentio-
                                                                                                   ning the license, but only for non-commercial purposes and
acute rhinosinusitis, chronic rhinosinusitis with nasal polyposis, chronic rhi-                    only in the original version. For further information: https://
nosinusitis without polyposis and adenoid hypertrophy 3.                                           creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                             71
C. Zeroli et al.




The main parameter used to assess sinonasal symptoms            considerably limit adherence to treatment, especially in
in AR is the Total Nasal Symptom Score (TNSS), which            paediatric patients, adolescents, and the elderly. The rec-
is derived from the sum of other marks for each of nasal        ommendation issued by the Pharmacovigilance Risk As-
congestion, sneezing, nasal itching, and rhinorrhea at each     sessment Committee of the European Medicines Agency
time point, using a four point scale (0-3), where a score of    states that BDP has a better profile, compared with all corti-
0 indicates no symptoms, 1 mild symptoms that are easily        costeroids, with respect to the risk of drug interactions and
tolerated, 2 awareness of symptoms which are bothersome         subsequent adrenal repercussions (Cushing’s syndrome
but tolerable, and 3 is reserved for severe symptoms that       and HPA axis suppression), which has resulted in changes
are hard to tolerate and interfere with daily activity.         to the Summary of Product Characteristics 6. With regards
Another important score used in clinical practice is            to the safety profile, it has been demonstrated 7 that BDP is
SNOT-22, which captures symptom severity, social and            well tolerated at the level of the nasal mucosa 8. The poten-
emotional impact, productivity, and sleep consequences of       tial risk of drug interaction of BDP is low as the drug has
CRS. Items are scored from 0 (no problem) to 5 (problem         limited systemic bioavailability: this has been confirmed
as bad as it can be) and summed to form a total score of 0      by demonstrating lower systemic exposure with intranasal
to 110. The main parameter used to assess sinonasal symp-       administration than with oral inhalation 2,9. Glucocorticoids
toms in CRS is the ability to undergo multiple formula-         remain the most effective anti-inflammatory drugs avail-
tions, such as nasal sprays, aerosols, dry powder inhalers,     able for the treatment of allergic diseases and it has been
and ointments that can deliver a powerful, localised anti-      difficult to find other therapies that are near as effective.
inflammatory effect. The intranasal administration of drugs     The use of combination of INCs and topical antihistamine
has been increasingly widespread in recent years, both due      medications has not revealed any new safety issues. Use of
to the availability of molecules with specific activity on      INCs with topical decongestants has some limited effects
the airways and the numerous technological innovations          of tachyphylaxis and rebound congestion 9. To date, no one
that have increased the efficiency of devices accessible in     has carried out a literature review regarding the duration
clinical practice. Among the several corticosteroid intrana-    and dosage of BDP therapy: our review aims to summarise
sal sprays, beclomethasone dipropionate (BDP) is one of         all the publications that have dealt with this topic to under-
the most widely prescribed and represents a possible “first     stand the current state of the literature and to help deter-
line of treatment”, since this molecule has an excellent ef-    mine the optimal dose of BDP and the best administration
ficacy and safety profile with decades of experience. The       regimen for nasal disease.
mechanism of action is a combination of anti-inflammatory
effects (by reducing pro-inflammatory gene transcription
and increasing anti-inflammatory gene transcription and         Materials and methods
reducing airway inflammatory cell infiltration) and sup-        PubMed was searched for articles written exclusively in
pression of the production of pro-inflammatory mediators,       English, including randomised clinical trials, cohort stud-
cell chemotactic factors and adhesion molecules 4. Patients     ies, meta-analyses, case reports, and case series about ef-
with nasal chronic inflammatory diseases often require          ficacy and safety, duration and dosage of BDP therapy, and
long-term strategies to control symptoms: the nasal ab-         excluding articles about BDP hydrofluoroalkane (HFA)
sorption from BDP improves local long-time efficacy but         and articles about asthma.
although the safety profiles of INCs are well established,      Search criteria included all occurrences of the following
there is some concern regarding the potential for systemic      terms in the title or abstract: BDP, intranasal corticosteroid,
complications associated with long-term treatment. These        nasal spray, aerosol, efficacy, safety, once-daily, chronic
concerns are based primarily on the systemic adverse            rhinosinusitis, allergic rhinitis and randomised controlled
events (AEs) that have been reported with oral and high-        trial. The corresponding results in the literature starting
dose inhalation corticosteroids, including growth inhibition    from 2010 were examined for admissibility and 64 articles
and hypothalamic-pituitary-adrenal (HPA) axis suppres-          were identified: 16 were assessed for eligibility. Finally, af-
sion. Nevertheless, the potential drug interaction risk of      ter applying the above-mentioned inclusion/exclusion cri-
BDP is low since the drug has limited systemic bioavail-        teria, 4 publications were analysed (Fig. 1) 4,10-12,13.
ability 5. The success of inflammatory disease management
with intranasal medications depends on the activity of the
drug and its pharmacokinetic and pharmacodynamic prop-
                                                                Results
erties 2. For INCs, these AEs are certainly less frequent and   The characteristics of the four articles included are shown
less serious than those observed with oral steroids, but can    in Table I. Two of the articles analysed were multicentric



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                                                                                                                                                                 Topical nasal steroids




                                                                                                one was a randomised, double-blind, clinical study. Sam-
                                                                                                ple sizes varied between 50 to 126. All studies included
                                                                                                patients of both genders older than 12 years.
                                                                                                Regarding treatment protocol, the total drug dose ranged
                                                                                                between 200 µg/day to 400 µg/day administered twice dai-
                                                                                                ly in all studies. Two of the four studies analysed patients
                                                                                                on BDP therapy in nasal spray formulation, one study aero-
                                                                                                sol only, and one compared aerosol and nasal spray.
                                                                                                In all studies, the duration of treatment ranged from 2 to 52
Figure 1. Process of selection of publications.                                                 weeks. Two articles referred to patients with AR and two
                                                                                                articles to patients with CRS.
                                                                                                The study by Sonnemann et al. found significant improve-
studies and the other two single-center studies. Three were                                     ment in the TNSS of patients treated with BDP nasal spray
randomised, double-blind, placebo controlled studies and                                        (p < 0.001). Furthermore, QoL was evaluated with a ques-


Table I. Summary of the most significant studies of BPD nasal spray or aerosol in patients with sinonasal disease.
 Reference Study design          Single         Patient’s Patient Pharmaceutical Frequency Daily dose                                           Weeks of           Parameters
                                centre or      population disease            form              daily      (microgram/                           treatment         improved with
                              multicentric       sample                                                        day)                                                 treatment
                                  study                                                                                                                            (parameters
                                                                                                                                                                  improved/total
                                                                                                                                                                 parameter of the
                                                                                                                                                                  score, p value)
 Sonnemann        Randomised,          Multicentre            50            AR           Nasal spray              2               320                2               TNSS (4/4,
 et al.,          double blind,                                                                                                                                      p < 0.001)
 2014 10             control,
                  placebo study

 Weinstein et     Randomised,          Multicentre           126            AR             Aerosol                1               320                52              QoL (1/14,
 al., 2014 11     double blind,                                                                                                                                      p = 0.008)
                     control,
                  placebo study
                                                                                                                                                                     TNSS (4/4,
                                                                                                                                                                     p < 0.001)
 Chong et           Review of         Single centre           55            CRS          Nasal spray              2               400                26              PNSS (4/4,
 al., 2016 4       randomised,                                                                                                                                       p = 0.008)
                  double blind,
                     control,
                  placebol trials
                                                                                                                                                                   Days on which
                                                                                                                                                                patients required no
                                                                                                                                                                 rescue medication
                                                                                                                                                                      (p .009)
 Rezaeian et       Randomised,        Single centre           60            CRS          Nasal spray              1               200                8         Higher percentage of
 al., 2021 12      double blind,                                                          Aerosol                                                               days with an overall
                    clinical trial                                                                                                                             nasal blockage score
                                                                                                                                                               on waking minor of 2
                                                                                                                                                                      (p .013)
                                                                                                                                                               Peak nasal inspiratory
                                                                                                                                                                flow measurements
                                                                                                                                                                     (p < 0.05)
                                                                                                                                                               - SNOT22 (p < 0.05)
                                                                                                                                                               - Lund-Mackay score
                                                                                                                                                                    (p < 0.05)
AR: allergic rhinitis; CRS: chronic rhinosinusitis; TNSS: total nasal symptoms score (nasal congestion, sneezing, nasal itching, and rhinorrhoea); PNSS: physicians nasal symptoms score.




                                                                                                                                                                                      73
C. Zeroli et al.




tionnaire in which the frequency of brushing of nose pa-           patients treated with BDP aerosol versus BDP nasal spray
rameter varied in a statistically significant way after treat-     (p = 0.041) and that the changes of the LM and SNOT‐22
ment (p = 0.008), while the other 13 parameters improved           scores in the BDP-aerosol group were higher than the BDP-
but not significantly. Those parameters were: frequency            nasal spray group (p < 0.05). Efficacy and tolerability were
of handkerchief use (p = 0.568), rubbing eyes and nose             measured indirectly by collecting data relating to AEs, show-
(p = 0.999), bad sleep (p = 0.878), bad work performance           ing that only two patients receiving BDP aerosol complained
(p = 0.328), fatigue (p = 0.690), thirst (p = 0.178), lack of      of slight nasal obstruction and no AEs were recorded in the
concentration (p = 0.389), general well-being (p = 0.462),         group of patients treated with BDP nasal spray 12.
headache (p = 0.081), bad temper (p = 0.549), general dis-
concertment (p = 0.099), frustration (p = 0.195) and reac-         Discussion
tions of others to the allergy (p = 0.377).
At the end of the study, patients assessed both efficacy and       CRS and AR are very common pathologies which require
tolerability with a score of 0 (no efficacy, bad to tolerate),     chronic treatment and therapies that have good efficacy and
1 (moderate efficacy, moderate tolerability), 2 (good effica-      safety. The first line treatment is nasal lavage combined
cy, good tolerability), and 3 (very good efficacy, very good       with INCs. In the literature, studies have shown that the ef-
tolerability): the mean score values showed that the percep-       ficacy of different INCs is very similar 13. While this is true,
tion of efficacy and tolerability were good 10. The study by       there are subtle nuances that should be considered when
Weinstein et al considered TNSS as the efficacy parameter          selecting the most appropriate INC. It is therefore assumed
which showed improvement in nasal congestion, sneezing,            that patients, considering their preferences, tend to change
nasal itching, and rhinorrhoea (p < 0.001) in patients treated     the way they use the INC spray based on sensory percep-
with aerosol BDP compared to placebo. Furthermore, the             tions and efficacy. The prescription should be adapted ac-
Physician Nasal Symptom Score (PNSS), defined as the sum           cording to bioavailability, the intranasal environment and
of the scores for four individual physician-assessed nasal         factors influencing patient adherence. BDP has been shown
symptoms obtained by questioning patients and with ear,            to have good bioavailability and good tolerability in terms
nose, and throat examinations (using a 0-3 scale) was also         of sensory perception.
improved in all 4 parameters (p = 0.008). QoL improved af-
ter 52 weeks of treatment, but was not statistically significant   Dosage
(p = 0.130). Regarding tolerability, the AEs related to aerosol    Regarding the dosage of INC, there is no established con-
therapy were epistaxis (10.6%), and it was concluded that          sensus on the maximum daily dose and the number of ad-
the drug is safe and effective 1. The study by Chong et al.        ministrations. Our review showed that any dose of BDP in
reported a significant improvement in days in which AR pa-         the range analysed (200 µg/day to 400 µg/day administered
tients required no rescue medication (p = 0.009) and higher        twice daily) was well tolerated. As far as the number of dai-
percentage of days with an overall “nasal blockage score           ly administrations is concerned, two studies considered two
on waking” of < 2 (p = 0.013). BDP nasal spray was ef-             administrations, and two only one administration. Since the
fective based on the physician’s assessments of symptoms           outcomes are expressed in different ways and with differ-
and polyp score at all clinic visits. In this study, safety and    ent parameters, the possibilities for comparison are limited.
tolerability were measured indirectly by collecting AE data,       However, comparing the two articles that used BDP at 320
showing that the only drug-related AE was epistaxis 4. The         microgram/day as an outcome parameter, both with one
article by Rezaeian 12 found improvement from baseline in          and two administrations, TNSS improved significantly.
both groups comparing the basal BDP aerosol and spray              A cycle of 20 days per month for 3 months can be repeated
scores of SNOT-22 and Lund-Mackay (LM) score (a radi-              after 1 month interruption.
ological score assessing opacification of a paranasal sinus
and the osteo-meatal complex). They were significantly de-         Efficacy, safety and tolerability
creased in the BDP-aerosol group compared with the BDP-            In the literature, the assessment of the safety profile and
nasal spray group (p < 0.05). It also compared the values of       tolerability has usually included AEs. The efficacy is es-
SNOT-22 and LM score before and after treatment with BDP           tablished by evaluating the improvement of the symptoma-
aerosol and BDP nasal spray, finding a lower score in these        tologic parameters. The studies we analysed showed that
two scores in both groups of patients, although not statisti-      treatment with BDP is not associated with serious AEs and
cally significant (p > 0.05). However, comparing the values        is characterised by good safety and tolerability.
of LM score and SNOT-22 between the two groups of pa-              As far as efficacy is concerned, the studies evaluated different
tients, it emerged that LM score was significantly lower in        outcomes expressed with different scores. The most widely



74
                                                                                                                           Topical nasal steroids




used score was the TNSS which improved after therapy in all       dures being performed in accordance with the requirements
4 of its subgroups: nasal congestion, sneezing, nasal itching,    of the World Medical Association’s Declaration of Helsinki.
and rhinorrhoea. Chong et al. analysed 3 specific parameters:
days on which patients required no rescue medication, high-       References
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