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29th June 2022
Questions over the added value of combining an intranasal antihistamine to mono-therapy with an inhaled steroid have been raised by a systematic review and meta-analysis by South Korean researchers.
Allergic rhinitis (AR) is characterised by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhoea. The disorder affects between 10 to 30 percent of children and adults in the United States and other industrialised countries and can can be either seasonal (SAR) or perennial (PAR).
A 2020 AR management guideline recommended that in patients with SAR, the combination of an intranasal corticosteroid (INCS) and an intranasal antihistamine (INAH) or an INCS alone would be an appropriate initial therapeutic choice. Furthermore, the guideline authors suggested that because the combination had a faster onset of action, it was likely to be preferred by patients. In fact, the guidelines do specifically advocate the combination, but only for patients with moderate-to-severe symptoms. A 2019 systemic review supported both the efficacy and superiority of combing the intranasal antihistamine, azelastine and fluticasone for a reduction in patient-reported symptom scores in allergic rhinitis, it did not include any other intranasal antihistamines.
As a result, for the present systematic review the Korean team searched on PubMed, EMBASE and the Cochrane Central Register of Controlled trials, for either randomised or non-randomised trials that included other types of INAH in combination with nasal corticosteroids and considered. In addition, the team also examined trials that included data on the adverse events of both treatments.
Intranasal antihistamines and treatment outcomes
The search identified 13 relevant randomised, controlled trials, 10 of which reported differences in symptom scores and 12 that described adverse events. Two other intranasal antihistamines identified and included in the analysis were bepotastine and olopatadine.
When compared to mono-therapy with an INCS, the combination of an INCS/INAH, reduced the mean morning and evening 12-hour total nasal symptom score (TNSS) more significantly (mean difference, MD = -0.44, 95% CI -0.61 TO -0.27, p < 0.00001) than INCS treatment alone. In addition, the combination also significantly reduced the total ocular symptom score (MD = -0.62, 95% CI -1.05 to -0.19, p = 0.005).
In comparison to INCS mono-therapy, combination treatment also significantly improved the total mean rhinoconjuctivitis quality of life score (MD = -0.24, 95% CI -0.42 to -.06, p = 0.009).
However, despite the enhanced benefit from the combination, it was found to be associated with a significantly greater risk of treatment-emergent adverse effects compared to INCS mono-therapy such as dysgeusia, i.e., a bad/bitter taste in the mouth or throat (relative risk, RR = 1.52, 95% CI 1.28 – 1.81, p < 0.00001).
The authors noted that while the combination of an INCS/INAH was significantly better at alleviating nasal and ocular symptoms, as well as improving quality of life compared to INCS mono-therapy, the improvements did not reach the minimal clinically important difference for either total nasal symptoms or rhinoconjuctivitis quality of life score.
As a result of these findings, the authors concluded that further studies are needed to verify the potential utility of the INCS/INAH combination compared to INCS mono-therapy.
Kim M et al. Intranasal antihistamine and corticosteroid to treat in allergic rhinitis: A systematic review and meta‐analysis Allergy 2022