• Seasonal allergic rhinitis

Complaint relief with modern non-sedating antihistamines

Allergic rhinitis (AR) is one of the most common allergic diseases worldwide. Every year during the pollen season, many people suffer from sneezing attacks, runny nose, watery eyes and nasal congestion. Modern second-generation H1 antihistamines are an evidence-based treatment option for AR. This is also the conclusion of a systematic review by a Canadian research team published in the Annals of Allergy, Asthma & Immunology in 2023.

The clinical manifestations of allergic rhinitis (AR) are caused by exposure to allergens through an IgE-mediated immune cascade. AR is divided into a seasonal and a perennial form depending on whether the symptoms occur in connection with certain seasons or all year round [1]. Tree and grass pollen from wind-pollinated plants are the main triggers of seasonal AR. The short and medium-term therapeutic goal is to be symptom-free. The use of second-generation H1 antihistamines (box) is recommended in preference to the older, more sedating first-generation antihistamines as first-line treatment for AR. For moderate to severe AR, intranasally administered glucocorticoids and/or intranasally administered antihistamines can also be used.

Antihistamines are inverse agonists at the H1 histamine receptor, i.e. they stabilize the receptor in its inactive conformation. As a result, they neutralize the effects of histamine and alleviate allergic symptoms. The older first-generation H1 antihistamines have pronounced anticholinergic and sedative effects and have many interactions with alcohol and other medications. They cross the blood-brain barrier and enter the brain, where they trigger central side effects such as tiredness, drowsiness and dizziness. Second-generation drugs are generally specific for the H1 receptor and are less attenuating. They are therefore also referred to as “non-sedating antihistamines”, but can also rarely cause drowsiness. They do not cross the blood-brain barrier, are specific for the H1 receptor and do not have an anticholinergic effect. They also have a longer duration of action of 12 to 24 hours and therefore only need to be administered once a day.
to [11,12]

Evidence for 2nd generation oral H1 antihistamines

Researchers at the Allergy Research Unit of the Kingston General Health Research Institute in Ontario (Canada) have summarized several clinically relevant studies and meta-analyses for various newer H1 antihistamines in AR. With the exception of rupatadine, all included active substances are authorized in Switzerland [2]: Fexofenadine since 1997, desloratadine and levocetirizine since 2001, bilastine since 2011. In the following, Linton et al. overview of the evidence included:

  • Fexofenadine: In a meta-analysis published in 2011 based on 8 randomized controlled double-blind trials (RCTs) with a total of 3532 participants, the efficacy of fexofenadine in AR was evaluated using the total symptom score (TSS) and the individual symptom score. Fexofenadine had a positive effect on all endpoints (p<0.001) and no significant differences were found with regard to adverse events (AE) compared to placebo (p=0.75) [3].
  • Desloratadine: In 2007, a meta-analysis of RCTs was conducted to evaluate the efficacy of desloratadine in the treatment of AR. A total of 13 studies with 3108 participants were included in this meta-analysis. Desloratadine led to a significant reduction in the total symptom score (TSS) (p=0.004), the total nasal symptom score (TNSS) (p<0.001) and nasal congestion (p=0.005) compared to placebo [4].
  • Levocetirizine: In a meta-analysis published in 2017, possible sedative effects of levocetirizine were evaluated based on 48 studies with a total of 18,014 participants. Compared to placebo, levocetirizine showed a moderate sedative effect (relative risk [RR]: 1.67; 95% confidence interval [KI], 1.17-2.38), but compared to first-generation antihistamines, levocetirizine had a less sedative effect and was associated with a smaller change in reaction time (mean difference: 250.76 seconds; 95% CI, 338.53-162.98) [5].
  • Bilastine/cetirizine/fexofenadine: In a phase II RCT published in 2010, the effect of bilastine was compared with that of cetirizine, fexofenadine and placebo on the TNSS after grass exposure. This study involved 75 people with seasonal allergic rhinitis. Bilastine and fexofenadine were found to have a similar effect on the TNSS in the first four hours after administration, but bilastine and cetirizine were significantly more effective than fexofenadine 22-26 hours after administration [6].
  • Bilastine/Cetirizine: Another large RCT published in 2009 was conducted to compare the efficacy and safety of Bilastine and Cetirizine after a treatment period of 14 days. This study included 683 participants with seasonal rhinitis. The clinical outcomes were the area under the curve of the TSS (TSS-AUC) and individual symptom scores. The reduction in TSS-AUC was similar for bilastine and cetirizine and significantly greater for both compared to placebo (p<0.001). The symptoms drowsiness (p<0.001) and fatigue (p<0.02) were significantly more pronounced in the patients in the group treated with cetirizine than in the group treated with bilastine [7]. A similar study was published in 2012 [8]: 650 participants with perennial rhinitis were included in this study, but the treatment duration was four weeks. In this study, the mean AUC of the 6-symptom total values was also significantly reduced in both groups compared to baseline versus placebo (p<0.05).
  • Rupatadine: A further meta-analysis of several RCTs evaluated the efficacy and safety of rupatadine in AR. 10 studies with 2573 patients were included. As a result, rupatadine showed a favorable benefit-risk profile in the treatment of AR. The clinical outcomes were TSS, TNSS and individual nasal and ocular symptom scores [9].

There is also increasing evidence for the use of second-generation oral H1 antihistamines in certain patient groups, such as children. In 2021, a study of ≤12-year-olds compared the side effect risks of second-generation antihistamines with those of the first generation and montelukast or placebo [10]. 45 studies published in the period 1989-2017 were included. Second-generation antihistamines proved to be safer and better tolerated. Cetirizine had the most pronounced sedative effect of the new generation of antihistamines.

Literature:

  1. Linton S, Hossenbaccus L, Ellis A: Evidence-based use of antihistamines for treatment of allergic conditions. Ann Allergy Asthma Immunol 2023; 131(4): 412-420.
  2. Swissmedic: Medicinal product information, www.swissmedicinfo.ch,(last accessed 26.04.2024)
  3. Compalati E, Canonica GW: Efficacy and safety of rupatadine for allergic rhino-conjunctivitis: a systematic review of randomized, double-blind, placebo-controlled studies with meta-analysis. Curr Med Res Opin 2013; 29: 1539-1551.
  4. Canonica GW, et al: Efficacy of desloratadine in the treatment of allergic rhinitis: a meta-analysis of randomized, double-blind, controlled trials. Allergy 2007; 62: 359-366.
  5. Snidvongs K, et al: Sedative effects of levocetirizine: a systematic review and meta-analysis of randomized controlled studies. Drugs 2017; 77: 175-186.
  6. Horak F, et al: The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber. Inflamm Res 2010; 59: 391-398.
  7. Kuna P, et al: Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo for the symptomatic treatment of seasonal allergic rhinitis: a randomized, double-blind, parallel-group study. Clin Exp Allergy 2009; 39: 1338-1347.
  8. Sastre J, et al: Bilastine Study Group. Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo in the treatment of perennial allergic rhinitis. Curr Med Res Opin 2012; 28: 121-130.
  9. Compalati E, et al: Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Int Arch Allergy Immunol 2011; 156: 1-15.
  10. Miligkos M, et al: Newer-generation antihistamines and the risk of adverse events in children: a systematic review. Pediatr Allergy Immunol 2021; 32: 1533-1558.
  11. Zuberbier T, et al: [S3 Guideline Urticaria. Part 2: Therapy of urticaria – German-language adaptation of the international S3 guideline]. J Dtsch Dermatol Ges 2023; 21(2): 202-216.
  12. PharmaWiki, www.pharmawiki.ch,(last accessed 26.04.2024).

FAMILY PHYSICIAN PRACTICE 2024; 19(5): 34-35

Autoren
  • Mirjam Peter, M.Sc.
Publikation
  • HAUSARZT PRAXIS
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