Our systematic review of the effectiveness of intranasal corticosteroids versus oral H1
receptor antagonists (antihistamines) for allergic rhinitis identified 18 randomised controlled trials that met the inclusion criteria. The meta-analysis of 16 evaluable trials confirmed that intranasal corticosteroids were significantly more effective at relieving nasal blockage, discharge, and itch, and postnasal drip than were oral antihistamines. Furthermore, all these results were homogeneous between studies. This indicates that an analysis of pooled data from clinical trials strongly supports the clinical suspicion that intranasal corticosteroids are more effective than oral antihistamines for such nasal symptoms.1
Intranasal corticosteroids were also more effective at relieving sneezing and at reducing total nasal symptoms than oral antihistamines, but there was significant heterogeneity between studies. Some heterogeneity could be accounted for by differences in scoring symptoms, although only one of the 13 studies showed that oral antihistamines produced greater relief of sneezing than did intranasal corticosteroids, and none of the nine studies showed that oral antihistamines significantly improved total nasal symptom scores. Despite the heterogeneity, we suggest that the pooled data favour the use of intranasal corticosteroids for relieving nasal symptoms.
Two studies met the inclusion criteria, but we were unable to obtain sufficient data for analysis.26,27
Both of these studies favoured intranasal corticosteroids for treating allergic rhinitis, and inclusion of these studies was unlikely to have altered the combined outcomes.
The various studies, however, measured symptom scores on different scales. For example in the study by Géhanno and Desfougeres the benefit from intranasal corticosteroids was equivalent to an additional 1.8 days symptom free per week.24
We believe that effects of this magnitude are clinically important.
The results of the pooled data on eye symptoms are surprising as there was no difference between the effectiveness of intranasal corticosteroids and oral antihistamines, although there was significant heterogeneity. Subgroup analysis suggested that this heterogeneity was not due to the use of different intranasal corticosteroids and oral antihistamines in the various trials. In some trials, however, the effect of each treatment was expressed as a mean score over the whole study period of 6 to 8 weeks and in others as the mean score in the last 2 weeks of an intervention period of 8 weeks. The stratified analysis indicated that much of the heterogeneity resulted from those studies where eye symptoms had been averaged over the entire duration of treatment. A possible explanation for this observation is the difference in the onset of action between intranasal corticosteroids and oral antihistamines. However, the difference in onset may be much smaller than commonly believed.44
Although the effect of oral antihistamines on the suppression of histamine induced wheal and flare reactions is rapid, the clinical onset in seasonal allergic rhinitis may take up to 5 hours.45
Furthermore, although intranasal corticosteroids were previously thought to take 3-10 days before a beneficial effect was observed, recent studies have shown significant relief of nasal symptoms in 12-24 hours.46,47
In addition, continuing treatment with intranasal corticosteroids may lead to a significant inhibition of the early nasal response as well as almost total inhibition of the late nasal response.48
Briefly, we believe that differences in onset between the intranasal corticosteroids and oral antihistamines might explain the observed heterogeneity of the subgroup analysis, but we are not convinced that these differences in onset of action translate into important clinical differences, for the reasons outlined.
Despite these reservations the results do not support the widely held view that oral antihistamines are superior to intranasal corticosteroids for controlling eye symptoms in allergic rhinitis.7
We calculated that there was no difference between these treatment modalities when eye symptoms were measured. Intranasal corticosteroids may improve eye symptoms by increasing nasolacrimal drainage, or there may be an effect from absorption of the corticosteroid.
Intranasal corticosteroids are considered safe. Local adverse effects are usually mild (mucosal irritation, epistaxis), and nasal septal perforation is exceptionally rare.49
Clinical and histopathological examination of nasal mucosa up to 5.5 years of continuous budesonide use have failed to show significant changes.50
Intranasal corticosteroids can result in systemic bioavailability,51
but studies have failed to show significant effects on serum markers of bone metabolism,52
short term bone growth,53
or cortisol concentrations after stimulation by adrenocorticotrophic hormone.54
First generation oral antihistamines are safe, but sedative and anticholinergic effects may be troublesome.55
Second generation (non-sedating or low-sedating) oral antihistamines do not have these effects and are well tolerated. Near fatal and fatal arrhythmias have been reported with terfenadine and astemizole,55
and these drugs are contraindicated in patients with heart or liver disease or when there is concomitant treatment with drugs that inhibit the hepatic cytochrome P
The cost effectiveness of intranasal corticosteroids versus oral antihistamines was assessed in three randomised controlled trials on the treatment of allergic rhinitis. An American study showed that if a patient used terfenadine for more than 11 to 22 days, then fluticasone was a more cost effective choice.56
Two cost effectiveness analyses performed in Canada produced cost effective ratios of 1:2.5 and 1:5.7 in favour of fluticasone versus terfenadine and loratadine respectively.57
We were not able to perform such an analysis on our data, but we did compare the mean daily cost of oral antihistamines in Australia (by asking pharmacists in four Australian states) with the mean daily cost of intranasal corticosteroids (based on Australian pharmaceutical benefits schedule). The mean daily cost of oral antihistamines was 4.5 times that of intranasal corticosteroids. We believe that the results of the North American studies and our data suggest that intranasal corticosteroids are more cost effective than oral antihistamines in the first line treatment of allergic rhinitis. There may be a role for oral antihistamines as ancillary treatment, particularly if eye symptoms or nasal itch are not controlled by intranasal corticosteroids.