Question

Should any specific combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid vs. other combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid be used for the treatment of allergic rhinitis?

Population:

Patients with allergic rhinitis

Intervention:

any specific combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid

Comparison:

other combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid

Main outcomes:

Nasal symptoms
Ocular symptoms
Quality of life
Adverse events (any)
Serious adverse events

Setting:

Perspective:

Background:

There are two widely used fixed combinations of intranasal antihistamines + intranasal corticosteroids (INAH+INCS) – azelastine-fluticasone and olopatadine-mometasone, rendering important not only to provide recommendations at a class level but also on what may be the most indicated individual INAH+INCS

Conflict of interests:

AWMF conflict of interest declaration and management policies were applied, the assessment performed by the AWMF with guidance and help from Juan Jose Yepes Nuñez.

Assessment

Problem

Is the problem a priority?

Judgement

Research evidence

Additional considerations

Allergic rhinitis (AR) is a common condition affecting 18.1% of the population, and its symptoms can significantly reduce the quality of life and pose a high economic burden (mainly because of indirect costs related to lost school days and workdays). [Savoure] Studies of patients consulting general practitioners for AR reported that 18–48 % had symptoms that were not controlled by pharmacotherapy. [Bousquet, Bhattacharyya, Vandenplas] Despite the bothersome nature of symptoms, AR is often trivialized by the patient - only 45% seek medical advice or treatment for their condition, which results in under-treatment and poor control of symptoms. [Linneberg]

Problems related to disease

Economic burden
A systematic review performed to estimate the financial burden of AR in European countries [Linneberg] suggests that the GP services bore the majority of the direct costs for AR. However, the majority of the overall cost burden correspond to indirect costs caused by high absenteeism and presenteeism. In the United States, annual costs for medications for rhinitis patients can be estimated at approximately $1.3 billion. In total, direct costs are estimated to be >$4.6 billion for rhinitis management, including treatment, allergy testing, clinical visits and hospital procedures. [Roland] Similar findings were found for Asia. An analysis of the indirect costs associated with insufficiently treated AR and urticaria patients revealed an annual burden of USD 105.4 billion. This translates to a cost ranging from USD 1,137 to USD 2,195 per patient due to absenteeism and presenteeism [ Kulthanan]

Clinical burden The median prevalence of allergic rhinitis was found to be 18.1%, based on a dataset that included 310 reported prevalences. The prevalence of AR ranged from as low as 1.0% to as high as 54.5%.
  • In Africa, the prevalence of AR ranged from 3.6% to 22.8%.
  • In the Americas, the prevalence of AR spans from 3.5% to 54.5%.
  • In Asia, the reported prevalence of AR varies from 1.0% to 47.9%.
  • In Europe, the range of AR prevalence is from 1.0% to 43.9%.
  • In Oceania, the prevalence of AR ranged from 19.2% to 47.5%.
These statistics indicate that AR is a relatively common condition affecting a significant portion of the population, with variations in prevalence observed across different regions or studies. [Savouré]

References:
  • Bhattacharyya N. Incremental healthcare utilization and expenditures for allergic rhinitis in the United States. Laryngoscope. 2011;121(9):1830-3.
  • Bousquet J, Anto JM, Bachert C, et al. Allergic rhinitis. Nat Rev Dis Primers. Dec 3 2020;6(1):95. doi:10.1038/s41572-020-00227-0
  • Komnos, I. , Michali, M. , Asimakopoulos, A. , Basiari, L. and Kastanioudakis, I. (2019) The Effect of Allergic Rhinitis on Quality of Life in Patients Suffering from the Disease: A Case Control Study. International Journal of Otolaryngology and Head & Neck Surgery, 8, 121-131. doi: 10.4236/ijohns.2019.84014.
  • Kulthanan K, Chusakul S, Recto MT, Gabriel MT, Aw DCW, Prepageran N, Wong A, Leong JL, Foong H, Quang VT, Zuberbier T. Economic Burden of the Inadequate Management of Allergic Rhinitis and Urticaria in Asian Countries Based on the GA²LEN Model. Allergy Asthma Immunol Res. 2018 Jul;10(4):370-378. doi: 10.4168/aair.2018.10.4.370. PMID: 29949833; PMCID: PMC6021592.
  • Lee, G. N., Koo, H. Y. R., Han, K., & Lee, Y. B. (2022). Analysis of Quality of Life and Mental Health in Patients With Atopic Dermatitis, Asthma and Allergic Rhinitis Using a Nation-wide Database, KNHANES VII. Allergy, asthma & immunology research, 14(2), 273–283. https://doi.org/10.4168/aair.2022.14.2.273
  • Linneberg, A., Dam Petersen, K., Hahn-Pedersen, J., Hammerby, E., Serup-Hansen, N., & Boxall, N. (2016). Burden of allergic respiratory disease: a systematic review. Clinical and molecular allergy : CMA, 14, 12. https://doi.org/10.1186/s12948-016-0049-9
  • Roland LT, Wise SK, Wang H, Zhang P, Mehta C, Levy JM. The cost of rhinitis in the United States: a national insurance claims analysis. Int Forum Allergy Rhinol. 2021 May;11(5):946-948. doi: 10.1002/alr.22748. Epub 2020 Dec 10. PMID: 33300670; PMCID: PMC8062294.
  • Savouré M, Bousquet J, Jaakkola JJK, Jaakkola MS, Jacquemin B, Nadif R. Worldwide prevalence of rhinitis in adults: A review of definitions and temporal evolution. Clin Transl Allergy. 2022;12(3):e12130.
  • Speth, M. M., Hoehle, L. P., Phillips, K. M., Caradonna, D. S., Gray, S. T., & Sedaghat, A. R. (2019). Treatment history and association between allergic rhinitis symptoms and quality of life. Irish journal of medical science, 188(2), 703–710. https://doi.org/10.1007/s11845-018-1866-2
  • Vandenplas O, Vinnikov D, Blanc PD, Agache I, Bachert C, Bewick M, et al. Impact of Rhinitis on Work Productivity: A Systematic Review. J Allergy Clin Immunol Pract. 2018;6(4):1274-86.e9.

Desirable Effects

How substantial are the desirable anticipated effects?

Judgement

Research evidence

Additional considerations

Nasal symptoms

In a systematic review with network meta-analysis performed by Sousa-Pinto et al., the improvement of nasal symptoms was assessed in patients under fixed combinations of intranasal corticosteroids and intranasal antihistamines (INCS+INAH).

For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the total nasal symptom score (TNSS) results of 68 randomised controlled trials (RCTs). Azelastine-Fluticasone was associated with a non-significantly higher improvement in the TNSS when compared to Olopatadine-Mometasone (mean difference=-0.24; 95%CI=-0.75;0.26). Azelastine-Fluticasone displayed a 23% probability of resulting in a small clinically meaningful improvement when compared to Olopatadine-Mometasone.

For patients with perennial allergic rhinitis, no evidence was available.

Subgroup considerations: Studies including vs. not including patients with asthma

A subsequent subgroup analysis of the network meta-analysis performed by Sousa-Pinto et al. was performed, grouping trials according to whether they had excluded patients with asthma. The following results were found comparing azelastine-fluticasone to olopatadine-mometasone:



Subgroup considerations: Children and adolescents

Following a post-hoc analysis of a systematic review performed by Sousa-Pinto et al.:
  • For seasonal allergic rhinitis, azelastine-fluticasone was associated with no significant differences compared to olopatadine mometasone (MD=0.07; 95%CI=-0.64,0.78)
  • For perennial allergic rhinitis, no evidence was found

Ocular symptoms

In a systematic review with network meta-analysis performed by Sousa-Pinto et al., the improvement of ocular symptoms was assessed in patients under fixed combinations of intranasal corticosteroids and intranasal antihistamines (INCS+INAH).

For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the total ocular symptom score (TOSS) results of 21 RCTs. Azelastine-Fluticasone was associated with a non-significantly higher improvement in the TNSS when compared to Olopatadine-Mometasone (mean difference=-0.20;; 95%CI=-0.48;0.08). Azelastine-Fluticasone displayed a 56% probability of resulting in a small clinically meaningful improvement when compared to Olopatadine-Mometasone.

For patients with perennial allergic rhinitis, no evidence was available.

Subgroup considerations: Studies including vs. not including patients with asthma

A subsequent subgroup analysis of the network meta-analysis performed by Sousa-Pinto et al. was performed, grouping trials according to whether they had excluded patients with asthma. The following results were found comparing azelastine-fluticasone to olopatadine-mometasone:



Subgroup considerations: Children and adolescents

Following a post-hoc analysis of a systematic review performed by Sousa-Pinto et al.:
  • For seasonal allergic rhinitis, azelastine-fluticasone was associated with no significant differences compared to olopatadine mometasone (MD=-0.08; 95%CI=-0.62,0.45)
  • For perennial allergic rhinitis, no evidence was found

Overall symptoms

In a systematic review with network meta-analysis performed by Sousa-Pinto et al., the improvement of overall symptoms was assessed in patients under fixed combinations of intranasal corticosteroids and intranasal antihistamines (INCS+INAH).

The patient-reported outcome measure used to assess this outcome was the total symptom score (TSS), which includes nasal, ocular and other rhinitis symptoms. 

No studies directly comparing the effectiveness of different fixed combinations measured by the TSS were identified.

There was only one study comparing a fixed combination (azelastine-fluticasone) with placebo on patients with perennial allergic rhinitis, having the TSS as the outcome measure. In this study the TSS was computed as the sum of 4 nasal symptoms and an ocular symptom. The post-intervention median TSS at the end of the follow-up period was of 1.5 points for the azelastine-fluticasone group and of 5.0 points for the placebo group (corresponding to a decrease of 7.0 versus 3.0 points in the median TSS, respectively).

No studies assessing the effectiveness of olopatadine-mometasone on TSS improvement were identified.

Quality-of-life

In a systematic review with network meta-analysis performed by Sousa-Pinto et al., the improvement of quality-of-life was assessed in patients under fixed combinations of intranasal corticosteroids and intranasal antihistamines (INCS+INAH).

For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the rhinocojunctivitis quality of life questionnaire (RQLQ) results of 23 RCTs. Azelastine-Fluticasone was associated with a non-significantly higher improvement in the TNSS when compared to Olopatadine-Mometasone (mean difference=-0.19; 95%CI=-0.40;0.02). Azelastine-Fluticasone displayed a 56% probability of resulting in a small clinically meaningful improvement when compared to Olopatadine-Mometasone.

For patients with perennial allergic rhinitis, no evidence was available.

Subgroup considerations: Studies including vs. not including patients with asthma

A subsequent subgroup analysis of the network meta-analysis performed by Sousa-Pinto et al. was performed, grouping trials according to whether they had excluded patients with asthma. The following results were found comparing azelastine-fluticasone to olopatadine-mometasone:



Subgroup considerations: Children and adolescents

Following a post-hoc analysis of a systematic review performed by Sousa-Pinto et al.:
  • For seasonal allergic rhinitis, azelastine-fluticasone was associated with no significant differences compared to olopatadine mometasone (MD=0.05; 95%CI=-0.29,0.39)
  • For perennial allergic rhinitis, no evidence was found
The detailed certainty of evidence assessment can be found here.
The list of included references in the systematic review can be found here.


Undesirable Effects

How substantial are the undesirable anticipated effects?

Judgement

Research evidence

Additional considerations

Adverse events

In a systematic review with network meta-analysis performed by Sousa-Pinto et al., the frequency of patients developing at least one adverse event was assessed in patients under fixed combinations of intranasal corticosteroids and antihistamines (INCS+INAH).

A total of 80 randomised controlled trials (RCTs) reported data on the number of patients with seasonal allergic rhinitis reporting at least one adverse event. The meta-analytical incidence rate ratio comparing azelastine-fluticasone to olopatadine-mometasone was of 1.33 (95%CI=0.88;2.04) [35 more cases per 1000 persons; 95%CI = 13 fewer cases to 109 more cases per 1000 person-years. Trivial difference], corresponding to an effect that is not clinically meaningful.

For patients with perennial allergic rhinitis, no evidence was available.

In an additional analysis of pharmacovigilance data comparing azelastine-fluticasone and olopatadine-mometasone, the following results were found (right = more common with azelastine-fluticasone; left = more common with olopatadine-mometasone):


Subgroup considerations: Studies including vs. not including patients with asthma

A subsequent subgroup analysis of the network meta-analysis performed by Sousa-Pinto et al. was performed, grouping trials according to whether they had excluded patients with asthma. The following results were found comparing azelastine-fluticasone to olopatadine-mometasone:


Subgroup considerations: Children and adolescents

Following a post-hoc analysis of a systematic review performed by Sousa-Pinto et al.:
  • For seasonal allergic rhinitis, azelastine-fluticasone was associated with no significant differences compared to olopatadine mometasone (RR=1.07; 95%CI=-0.51,2.22);
  • For perennial allergic rhinitis, no evidence was available.
Serious adverse events

In a systematic review with network meta-analysis performed by Sousa-Pinto et al., the frequency of patients developing at least one serious adverse event was assessed in patients under INCS+INAH. However, the frequency of events was too scarce to perform network meta-analysis comparing individual medications.

The (non-pooled) frequency of serious adverse events per individual INCS+INAH is displayed in the following table. The provided interval are fully within the “trivial” category.


Subgroup considerations: Children and adolescents
Following a post-hoc analysis of a systematic review performed by Sousa-Pinto et al.:
  • For seasonal allergic rhinitis, 0 adverse events were observed for azelastine-fluticasone (173 participants; 1 RCT) and 0 adverse events were observed for olopatadine-mometasone (225 participants; 1 RCT);
  • For perennial allergic rhinitis, no evidence was available.
The detailed certainty of evidence assessment can be found here.
The list of included references in the systematic review can be found here.

Certainty of evidence

What is the overall certainty of the evidence of effects?

Judgement

Research evidence

Additional considerations

The certainty of evidence was moderate for 5 out of 5 analyses (all concerning seasonal allergic rhinitis):
  • Nasal symptoms (seasonal allergic rhinitis): Moderate
  • Nasal symptoms (perennial allergic rhinitis): No evidence
  • Ocular symptoms (seasonal allergic rhinitis): Moderate
  • Ocular symptoms (perennial allergic rhinitis): No evidence
  • Quality of life (seasonal allergic rhinitis): Moderate
  • Quality of life (perennial allergic rhinitis): No evidence
  • Adverse events (seasonal allergic rhinitis): Moderate
  • Adverse events (perennial allergic rhinitis): No evidence
  • Serious adverse events (seasonal allergic rhinitis): Moderate
  • Serious adverse events (perennial allergic rhinitis): No evidence

Values

Is there important uncertainty about or variability in how much people value the main outcomes?

Judgement

Research evidence

Additional considerations

Utility values
Symptoms
Regarding specific symptoms, in two studies, utilities (measured by VAS) were lower for severe nasal congestion and severe rhinorrhea compared to severe sneezing, severe throat itching, and severe itchy eyes (certainty of evidence: low). When utilities were elicited with the standard gamble technique, severe itchy eyes were rated by US patients as the least preferred AR symptom (certainty of evidence: low).



Studies of rating or ranking of outcomes

Adults
  • Regarding specific symptoms, in eleven out of fourteen studies, a nasal symptom was ranked as the most and/or second most important attribute (certainty of evidence: low-moderate). All of the analyzed nasal symptoms were ranked as the most or second most important attribute in at least one study. In particular, eight studies identified nasal congestion as the most important attribute (certainty of evidence: low-moderate).
  • An ocular symptom was ranked as the most or the second most important attribute in three studies out of thirteen. In particular, itchy eyes were identified as the most important or second most important in two studies (certainty of evidence: low). In five studies out of eight a non-nasal respiratory symptom (namely, breathing difficulties) was identified as the most or second most important attribute (certainty of evidence: moderate).

Children/caregivers sample
Seven studies assessing children or their caregivers were included in the relative importance analysis. Most of these studies only assessed symptom-related attributes. Similarly to the adult population, a nasal symptom was frequently ranked as the most or second most important attribute (certainty of evidence: low). In particular, nasal congestion was identified as the most important attribute in five studies (certainty of evidence: low).





Balance of effects

Does the balance between desirable and undesirable effects favor the intervention or the comparison?

Judgement

Research evidence

Additional considerations

Taking into account both benefits and harms of azelastine-fluticasone versus olopatadine-mometasone, we can consider the following:
  • Benefits in seasonal allergic rhinitis: In seasonal allergic rhinitis, azelastine-fluticasone has not been found to be significantly more effective in improving nasal or ocular symptoms (as assessed by the Total Nasal Symptom Score, TNSS, and the Total Ocular Symptom Score, TOSS), not quality-of-life (as assessed by the rhinoconjunctivitis quality of life questionnaire, RQLQ). The probability of azelastine-fluticasone resulting in a clinically meaningful small effect ranged from 23% (for the TNSS) to 56% (for the TOSS and the RQLQ). Certainty of evidence was moderate for all outcomes.
  • Harms in seasonal allergic rhinitis: Azelastine-fluticasone are associated with trivial harms comparatively to olopatadine-mometasone when considering the development of any adverse event (AE). Serious AE are very rare and most of those reported in randomised clinical trials have been judged unlikely to be related to the treatment.
No evidence was available for perennial allergic rhinitis.

Resources required

How large are the resource requirements (costs)?"

Judgement

Research evidence

Additional considerations

We conducted a survey, having received responses from specialists from 41 countries (mostly in Europe, America and Asia). In 36 of these countries, intranasal corticosteroids + intranasal antihistamines (INCS+INAH) were available. In 14 of these countries, both azelastine-fluticasone and olopatadine-mometasone were available.

The costs of being treated for one year with azelastine-fluticasone ranged from 32.4 US Dollars Power Purchase Parity (PPP) [Bangladesh] to 1209.0 USD PPP [Argentina] (assuming full adherence to treatment). This corresponds to weekly costs ranging from 0.62 USD PPP to 23.3 USD PPP. The yearly costs per country associated with the use of azelastine-fluticasone are displayed in the following map:


The costs of being treated for one year with olopatadine-mometasone ranged from 70.2 US Dollars Power Purchase Parity (PPP) [Israel] to 1455.84 USD PPP [Colombia] (assuming full adherence to treatment). This corresponds to weekly costs ranging from 1.35 USD PPP to 28.0 USD PPP. The yearly costs per country associated with the use of olopatadine-mometasone are displayed in the following map:


In 8 out of the 14 countries where both azelastine-fluticasone and olopatadine-mometasone were reported to be available, azelastine-fluticasone was associated with lower costs than olopatadine-mometasone:




References:
  1. https://www.lancsmmg.nhs.uk/medicines-library/olopatadine-hydrochloride-and-mometasone-furoate-monohydrate-ryaltris/
  2. Harrow B, Sedaghat AR, Caldwell-Tarr A, Dufour R. A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines. J Manag Care Spec Pharm. 2016 Dec;22(12):1426-1436. doi: 10.18553/jmcp.2016.22.12.1426. PMID: 27882840; PMCID: PMC10398247.


Certainty of evidence of required resources

What is the certainty of the evidence of resource requirements (costs)?

Judgement

Research evidence

Additional considerations

Given that combinations of intranasal steroids and antihistamines has been around for a long time, there is a reasonably high degree of certainty about the general costs. However, it should be noted that available evidence comes from a survey of experts.

Cost effectiveness

Does the cost-effectiveness of the intervention favor the intervention or the comparison?

Judgement

Research evidence

Additional considerations

We did not identify any studies that adequately addressed the cost-effectiveness of specific combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid vs. other combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid. There is no sufficient data in MASK-air on the VAS-EQ5D of patients treated with olopatadine-mometasone.

Equity

What would be the impact on health equity?

Judgement

Research evidence

Additional considerations

Availability

We conducted a survey, having received responses from specialists from 41 countries (mostly in Europe, America and Asia).

Intranasal corticosteroids + intranasal antihistamines (INCS+INAH) were reported to be available in 36 out of 41 countries. Azelastine-fluticasone was reported to be available in 34 out of the 36 countries. Olopatadine-mometasone was reported to be available in 16 out of the 36 countries.


Other equity-related aspects

We were able to map the following aspects related to equity.



Acceptability

Is the intervention acceptable to key interest-holders?

Judgement

Research evidence

Additional considerations

Compliance

Evidence from direct patient data:
In complete weeks of MASK-air reporting, there were 33.2% in which azelastine-fluticasone was used for 6 or 7 days. This compares with 5.4% of the weeks for olopatadine-mometasone.

Satisfaction
We found 1 study that addressed the acceptability of specific combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid vs. other combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid. [Fifer]
Satisfaction rate/Sensory attributes (Fifer-Australia)
- Participants using OLO/MOM (mean = 68.26, SE = 1.39) had significantly higher Treatment Satisfaction Index (TSI) than participants using AZE/FLU(M=62.78, SE = 0.70) (p < 0.001.
- Participants using OLO/MOM had significantly higher satisfaction scores than participants using AZE/FLU for 7 of the11 domains: immediate taste of medication, aftertastej of medication, smell of medication, irritation to nose, urge to sneeze,dripping out nose/down throat, and dryness of nose or throat.
- participants using OLO/MOM were more satisfied with their overall treatment compared to participants using AZE/FLU, particularly with sensory attributes, thus highlighting the suitability of OLO/MOM for people with AR who value sensory attributes
- Participants using AZE/FLU had higher importance scores on two domains, duration of effect and AR symptom control, while participants using OLO/MOM had higher importance scores on 8 domains; immediate taste of medication,aftertaste of medication, smell of medication, irritation to nose, urge to sneeze, dripping out nose/down throat, dryness ofnose or throat, convenience. There was no significant difference for the fast acting domain.

Evidence from direct patient data:
In the MASK-air dataset, there were 2694 days in which azelastine-fluticasone was used in monotherapy and for which patients provided information on how satisfied they were with their treatments. The median results of the visual analogue scale were of 82 (higher values indicating higher satisfaction) [IQR=24].
In the MASK-air dataset, there were 140 days in which olopatadine-mometasone was used in monotherapy and for which patients provided information on how satisfied they were with their treatments. The median results of the visual analogue scale were of 90 [IQR=18].
In multivariable linear regression models adjusted for the CSMS of the previous day (a proxy variable of the rhinitis control level before medication use) and for the patients’ ARIA score (an indicator of disease severity), azelastine-fluticasone was associated with higher VAS satisfaction than olopatadine-mometasone (average difference: 2.47; 95%CI=-2.18;7.12).

Co-medication rate

Evidence from direct patient data:
In the MASK-air dataset, in 50.9% of the days in which azelastine-fluticasone have been used, they have been used in comedication. This compares with 51.9% for olopatadine-mometasone. In multivariable linear regression models adjusted for the CSMS of the previous day (a proxy variable of the rhinitis control level before medication use) and for the patients’ ARIA score (an indicator of disease severity), azelastine-fluticasone was associated with higher odds of being used of co-medication compared to olopatadine-mometasone (OR=1.31; 95%CI=0.56;3.04).

Onset of action

We performed a rapid review of the literature and found the following results:


References:
1. Fifer S, Toh L, Barkate H, Aggarwal V, Borade D, Gordonsmith RH, Wu W, Morgan C, Young K. Patient Satisfaction and Sensory Attributes of Nasal Spray Treatments of Olopatadine Hydrochloride/Mometasone Furoate Monohydrate and Azelastine Hydrochloride/Fluticasone Propionate for Allergic Rhinitis in Australia - An Observational Real-World Clinical Study. Patient Prefer Adherence. 2023 Jan 15;17:141-151. doi: 10.2147/PPA.S389875. PMID: 36687019; PMCID: PMC9851056.

Feasibility

Is the intervention feasible to implement?

Judgement

Research evidence

Additional considerations

We did not identify any studies that adequately addressed the feasibility of specific combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid vs. other combination of an intranasal H1-antihistamine and an intranasal glucocorticosteroid.

Planetary health

What would be the impact on planetary health?

Judgement

Research evidence

Additional considerations

For branded products, both are manufactured in India (no difference between intervention and comparison). Olopatadine-Mometasone is distirbuted in a plastic vial, as opposed to Azelastine-Fluticasone, which is distributed in a glass vial.

Summary of judgements

Judgement

Problem

No

Probably no

Probably yes

Yes

Varies

Don't know

Desirable Effects

Trivial

Small

Moderate

Large

Varies

Don't know

Undesirable Effects

Trivial

Small

Moderate

Large

Varies

Don't know

Certainty of evidence

Very low

Low

Moderate

High

No included studies

Values

Important uncertainty or variability

Possibly important uncertainty or variability

Probably no important uncertainty or variability

No important uncertainty or variability

Balance of effects

Favors the comparison

Probably favors the comparison

Does not favor either the intervention or the comparison

Probably favors the intervention

Favors the intervention

Varies

Don't know

Resources required

Large costs

Moderate costs

Negligible costs and savings

Moderate savings

Large savings

Varies

Don't know

Certainty of evidence of required resources

Very low

Low

Moderate

High

No included studies

Cost effectiveness

Favors the comparison

Probably favors the comparison

Does not favor either the intervention or the comparison

Probably favors the intervention

Favors the intervention

Varies

No included studies

Equity

Reduced

Probably reduced

Probably no impact

Probably increased

Increased

Varies

Don't know

Acceptability

No

Probably no

Probably yes

Yes

Varies

Don't know

Feasibility

No

Probably no

Probably yes

Yes

Varies

Don't know

Planetary health

Reduced

Probably reduced

Probably no impact

Probably increased

Increased

Varies

Don't know


Type of recommendation

○

○

○

●

○

Conclusions

Recommendation

In patients with allergic rhinitis, the ARIA guideline panel suggests using the fixed-combination of azelastine-fluticasone over the fixed-combination of olopatadine-mometasone (conditional recommendation based on moderate certainty of evidence for seasonal allergic rhinitis).

Justification

This recommendation is mostly grounded (i) on a favourable balance of effects, (ii) acceptability of the azelastine-fluticasone.

Subgroup considerations

Children and adolescents: A post-hoc analysis of a systematic review performed by Sousa-Pinto et al. showed that, for children with seasonal allergic rhinitis, azelastine-fluticasone was associated with no significant differences compared to olopatadine mometasone in any of the assessed outcomes (TNSS, TOSS, RQLQ or adverse events) No serious adverse events were reported with the use of either drug. No evidence was found for perennial allergic rhinitis.

A subsequent subgroup analysis of the network meta-analysis performed by Sousa-Pinto et al. was performed, grouping trials according to whether they had excluded patients with asthma. For patients with seasonal allergic rhinitis, azelastine-fluticasone was not associated with a significantly higher improvement in TOSS or RQLQ in either subgroup compared to olopatadine-mometasone. A significantly higher improvement in the TNSS was, however, observed only in the subgroup including patients with asthma. No significant difference in the risk ratio of adverse events between the two drugs was observed in either subgroup and no serious adverse events were reported. No evidence was found for perennial allergic rhinitis.

Implementation considerations

In patients experiencing bitter taste with azelastine-fluticasone, olopatadine-mometasone may be preferred.

Monitoring and evaluation


Research priorities

- Need for studies in specific subgroups of participants or presentation of results by subgroup. Such subgroups include: children and adolescents (perennial allergic rhinitis), older patients, patients with multimorbidity (asthma and conjunctivitis), and patients from ethnic minorities.
- Need for studies - particularly randomised controlled trials - evaluating participants with mild allergic rhinitis and with perennial allergic rhinitis.
- Need for studies evaluating the cost-effectiveness and planetary health impact of the interventions.