Review question
We wanted to find out whether intranasal corticosteroids (steroids applied into the nose) are effective for the treatment of rhinitis that is not caused by allergy.
Background
Non-allergic rhinitis is a chronic disease of the nose, which is not caused by infection or allergies. People with non-allergic rhinitis experience symptoms that affect their quality of life, such as nasal obstruction, runny nose and sneezing. Non-allergic rhinitis patients can be divided into different subgroups who have different underlying causes for their disease. The underlying causes of non-allergic rhinitis are not fully understood, therefore treatment is often unsuccessful in these patients.
Topical (intranasal) corticosteroids are used with the aim of reducing inflammation. They are the most commonly prescribed drug in other chronic diseases of the nose and sinuses, such as allergic rhinitis and chronic rhinosinusitis. Intranasal corticosteroid treatment can be delivered with sprays or drops and for different time periods.
Study characteristics
We included 34 randomised controlled trials (RCTs) with a total of 4452 participants in this review. Most of the studies were relatively small, although the largest study had 983 patients in total. All of the patients were either adults or adolescents (aged between 12 and 18 years old) with non-allergic rhinitis. The studies looked at a range of types, doses and methods of administration (e.g. spray, drops) of intranasal corticosteroids. Nine studies were sponsored by the pharmaceutical industry or had commercial sponsors. One study was funded by the government. In several studies, the pharmaceutical industry or commercial sponsor may have provided medications, but the funding role was unclear. Funding was not reported in eight studies.
Key results
Intranasal corticosteroids compared with placebo
It is uncertain whether intranasal corticosteroids reduce patient-reported disease severity in non-allergic rhinitis patients compared with placebo when measured at up to three months. They may improve patient-reported disease severity compared with placebo at up to four weeks, however this evidence is of low certainty. Treatment with intranasal corticosteroids probably increases the risk of epistaxis (nosebleed) but there is no difference in the risk of other adverse effects. It is not possible to tell from this review whether there is a difference between the different concentrations, delivery methods or treatment plans of intranasal corticosteroids. There are no good-quality studies assessing changes in quality of life with intranasal corticosteroids.
Intranasal corticosteroids compared with other treatments
There is not enough evidence to know whether intranasal corticosteroid treatment is better, worse or the same as using other treatment strategies such as saline irrigation, intranasal antihistamines, capsaicin or ipratropium bromide for non-allergic rhinitis.
Certainty of the evidence
Overall, the evidence for intranasal corticosteroids compared with placebo for most outcomes was either low-certainty (our confidence in the effect estimate is low) or very low-certainty (our confidence in the effect estimate is very low). This was because most studies were very small and used different methods to measure the same outcome. This evidence is up to date to July 2019.
Overall, the certainty of the evidence for most outcomes in this review was low or very low. It is unclear whether intranasal corticosteroids reduce patient-reported disease severity in non-allergic rhinitis patients compared with placebo when measured at up to three months. However, intranasal corticosteroids probably have a higher risk of the adverse effect epistaxis. There are very few studies comparing intranasal corticosteroids to other treatment modalities making it difficult to draw conclusions.
Non-allergic rhinitis is defined as dysfunction and non-infectious inflammation of the nasal mucosa that is caused by provoking agents other than allergens or microbes. It is common, with an estimated prevalence of around 10% to 20%. Patients experience symptoms of nasal obstruction, anterior rhinorrhoea/post-nasal drip and sneezing. Several subgroups of non-allergic rhinitis can be distinguished, depending on the trigger responsible for symptoms; these include occupation, cigarette smoke, hormones, medication, food and age. On a cellular molecular level different disease mechanisms can also be identified. People with non-allergic rhinitis often lack an effective treatment as a result of poor understanding and lack of recognition of the underlying disease mechanism. Intranasal corticosteroids are one of the most common types of medication prescribed in patients with rhinitis or rhinosinusitis symptoms, including those with non-allergic rhinitis. However, it is unclear whether intranasal corticosteroids are truly effective in these patients.
To assess the effects of intranasal corticosteroids in the management of non-allergic rhinitis.
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 7); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 July 2019.
Randomised controlled trials (RCTs) comparing intranasal corticosteroids, delivered by any means and in any volume, with (a) placebo/no intervention or (b) other active treatments in adults and children (aged ≥ 12 years).
We used the standard methodological procedures expected by Cochrane. The primary outcomes were patient-reported disease severity and a
significant adverse effect - epistaxis. Secondary outcomes were (disease-specific) health-related quality of life, objective measurements of airflow and other adverse events. We used GRADE to assess the certainty of the evidence for each outcome.
We included 34 studies (4452 participants); however, only 13 studies provided data for our main comparison, intranasal corticosteroids versus placebo. The participants were mainly defined as patients with perennial rhinitis symptoms and negative allergy tests. No distinction between different pheno- and endotypes could be made, although a few studies only included a specific phenotype such as pregnancy rhinitis, vasomotor rhinitis, rhinitis medicamentosa or senile rhinitis. Most studies were conducted in a secondary or tertiary healthcare setting. No studies reported outcomes beyond three months follow-up. Intranasal corticosteroid dosage in the review ranged from 50 µg to 2000 µg daily.
Intranasal corticosteroids versus placebo
Thirteen studies (2045 participants) provided data for this comparison. These studies used different scoring systems for patient-reported disease severity, so we pooled the data in each analysis using the standardised mean difference (SMD). Intranasal corticosteroid treatment may improve patient-reported disease severity as measured by total nasal symptom score compared with placebo at up to four weeks (SMD -0.74, 95% confidence interval (CI) -1.15 to -0.33; 4 studies; 131 participants; I2 = 22%) (low-certainty evidence). However, between four weeks and three months the evidence is very uncertain (SMD -0.24, 95% CI -0.67 to 0.20; 3 studies; 85 participants; I2 = 0%) (very low-certainty evidence). Intranasal corticosteroid treatment may slightly improve patient-reported disease severity as measured by total nasal symptom score change from baseline when compared with placebo at up to four weeks (SMD -0.15, 95% CI -0.25 to -0.05; 4 studies; 1465 participants; I2 = 35%) (low-certainty evidence).
All four studies evaluating the risk of epistaxis showed that there is probably a higher risk in the intranasal corticosteroids group (65 per 1000) compared to placebo (31 per 1000) (risk ratio (RR) 2.10, 95% CI 1.24 to 3.57; 4 studies; 1174 participants; I2 = 0%) (moderate-certainty evidence). The absolute risk difference (RD) was 0.04 with a number needed to treat for an additional harmful outcome (NNTH) of 25 (95% CI 16.7 to 100).
Only one study reported numerical data for quality of life. It did report a higher quality of life score in the intranasal corticosteroids group (152.3 versus 145.6; SF-12v2 range 0 to 800); however, this disappeared at longer-term follow-up (148.4 versus 145.6) (low-certainty evidence).
Only two studies provided data for the outcome objective measurements of airflow. These data could not be pooled because they used different methods of outcome measurement. Neither found a significant difference between the intranasal corticosteroids and placebo group (rhinomanometry SMD -0.46, 95% CI -1.06 to 0.14; 44 participants; peak expiratory flow rate SMD 0.78, 95% CI -0.47 to 2.03; 11 participants) (very low-certainty evidence).
Intranasal corticosteroids probably resulted in little or no difference in the risk of other adverse events compared to placebo (RR 0.99, 95% CI 0.87 to 1.12; 3 studies; 1130 participants; I2 = 0%) (moderate-certainty evidence).
Intranasal corticosteroids versus other treatments
Only one or a few studies assessed each of the other comparisons (intranasal corticosteroids versus saline irrigation, intranasal antihistamine, capsaicin, cromoglycate sodium, ipratropium bromide, intranasal corticosteroids combined with intranasal antihistamine, intranasal corticosteroids combined with intranasal antihistamine and intranasal corticosteroids with saline compared to saline alone). It is therefore uncertain whether there are differences between intranasal corticosteroids and other active treatments for any of the outcomes reported.