Allergic Rhinitis: Challenges, Treatment Choices and Clinical Spotlight on Fexofenadine

Allergic Rhinitis: Global Trends and Regional Insights:

The prevalence of AR is up to 2-25% in children and 10-40% in adults worldwide. In developing countries, notably in Southeast Asia, the occurrence of AR is notably elevated, with rates ranging from 6% to 22% in India (2).

Diverse Risk Factors of AR:

Among the various allergic diseases, the prevalence of AR stands at approximately 55%, making it a prominent burden among various allergic conditions in India. Numerous factors, beyond general demographic considerations, have been identified as potential risk factors for AR. Exposure to allergens, whether perennial or seasonal, occurs in both indoor and outdoor environments. Seasonal allergic rhinitis (SAR) is primarily triggered by pollen from grass, trees, and weeds. On the other hand, perennial allergic rhinitis (PAR) is commonly caused by indoor factors such as house dust mites, pets, and molds (3). These diverse factors along with environmental and genetic factors collectively contribute to the complexity of understanding and addressing the risk profile associated with AR (10). Table (1) and Figure (2) show the allergen triggers and risk factors for AR in India (respectively).

Table 1: Allergen triggers for AR in India.

Navigating the Challenges in AR: Indian Context

Optimizing AR Management:

Due to the substantial disease burden associated with AR, the implementation of integrated care pathways is imperative to ensure a comprehensive approach to its management. The Ministry of Health and Family Welfare, Government of India, provides recommendations that encompass various treatment options, with a focus on environmental control measures and allergen avoidance (12). The repertoire of treatments available for AR includes oral antihistamines, intranasal corticosteroids, decongestants, chromones, anticholinergics, and antileukotrienes. Importantly, antihistamines are recommended for mild intermittent AR (1). These guidelines emphasize the necessity of tailoring treatment strategies according to the severity of the condition, emphasizing a holistic approach to AR management.

Fexofenadine: A Preferred Second-Generation Antihistamine:

Among the various antihistamines, fexofenadine, categorized as a second-generation antihistamine and a metabolite of terfenadine, is the preferred choice due to its diverse clinical advantages. It has received approval from the U.S. FDA for the treatment of AR and chronic idiopathic urticaria. Fexofenadine selectively antagonizes H1 receptors, modulates inflammatory mediators, exhibits reduced affinity for cholinergic and alpha-adrenergic receptors, and demonstrates a superior safety profile in comparison to other second-generation antihistamines (13).

Fexofenadine has demonstrated an absence of QT interval prolongation and arrhythmogenic effects, affirming its non-cardiotoxic nature. Its limited penetration of the blood-brain barrier contributes to diminished sedative effects compared to first-generation antihistamines, positioning it as a more favorable recommendation among the new generation of antihistamines. Notably, fexofenadine exhibits a distinctive characteristic by exerting minimal effect on cognitive and psychomotor functions, differentiating it from both first-generation and other second-generation antihistamines (14).

Anti-inflammatory action of Fexofenadine in AR- Beyond Anti-histaminic Activity:

Fexofenadine's clinical benefits are primarily ascribed to its antihistaminic properties, but it extends its additional therapeutic effect through anti-inflammatory mechanisms. By inhibiting intracellular adhesion molecule 1 (ICAM-1) expression promptly following allergen exposure, fexofenadine plays a crucial role in mitigating allergic inflammation. Furthermore, it demonstrates concentration-dependent inhibition of interleukin-6 (IL-6), a key mediator in the acute-phase response. At concentrations ≥ 0.25 μg/mL, fexofenadine disrupts Chemotactic Cytokine Ligand 5 (CCL5) and eotaxin, pivotal chemotactic factors recruiting inflammatory cells like eosinophils and basophils during the late-phase response. Additionally, at this concentration, fexofenadine suppresses peripheral blood leukocyte production of thymus and activation-regulated chemokine (TARC), a chemotactic cytokine (CC) chemokine with a potential role in sustaining allergic immune responses (15).

Clinical Evidence of Fexofenadine in AR:

• Fexofenadine Efficacious & Safe Across Different Dosage Strengths in Allergic Rhinitis: The efficacy and safety of fexofenadine was assessed through a 14-day, multicenter, placebo-controlled, double-blind trial. In this study, 570 patients with moderate to severe ragweed seasonal AR were randomly assigned to receive fexofenadine HCl (60, 120, or 240 mg twice a day) or a placebo at 12-hour intervals. The primary efficacy measure involved patients assessing a 12-hour reflective total symptom score before the evening dose (trough). Symptoms evaluated included nasal congestion; sneezing; rhinorrhea; itchy nose, palate, and/or throat; and itchy, watery, and red eyes on a 5-point scale. Across all dosage levels, fexofenadine HCl significantly improved the total symptom score (sum of the individual symptom scores, excluding nasal congestion) and individual nasal symptoms (nasal congestion) compared to the placebo. The trial findings concluded that Fexofenadine HCl is effective and safe for treating ragweed seasonal AR. (17)
• Fexofenadine efficacious in Allergic Rhinitis (AR)- An Indian Experience: In a study conducted on the Indian population, the efficacy of fexofenadine was assessed in two hundred patients experiencing allergic rhinitis. Patients were administered fexofenadine 120 mg once daily for AR over 7 days. The evaluation of efficacy relied on the symptom evaluation scale score (as 0-absent, 1-mild, 2-moderate, 3-severe, and 4-very severe) and medication effectiveness scale score (as 0-complete relief, 1-marked relief, 2-moderate relief, 3-slight relief, 4-no relief) at baseline, on the 3rd day, and the 7th day after completing the treatment. The results indicated that patients with allergic rhinitis receiving fexofenadine 120 mg once daily exhibited high efficacy, marked by significant relief or complete resolution of symptoms. The study concluded that fexofenadine demonstrates high effectiveness in treating allergic rhinitis in the Indian population (16).
• Fexofenadine More Effective than Chlorpheniramine: A comparative study conducted in Bidar, India, assessed the efficacy of fexofenadine versus chlorpheniramine maleate in 70 patients suffering from allergic rhinitis (AR). The enrolled patients were randomly assigned to two treatment arms; Group A received fexofenadine 120 mg tablet, and Group B received chlorpheniramine 4 mg tablet. After a 2-week follow-up, a statistically significant reduction in the severity of individual symptoms (sneezing, nasal obstruction, discharge, itching of nose and eyes) was observed in patients from Group A (100%) compared to Group B (92%) (P < 0.001) from the baseline. The study concluded that fexofenadine is more effective in relieving symptoms than chlorpheniramine, with fewer adverse effects than the latter (18).
• Fexofenadine Preferred Option for AR in India: 2024 Update: A cross-sectional, observational survey was conducted to examine the perspectives and clinical preferences of Indian physicians (n=1608), including available treatments for AR apart from understanding the clinical landscape of the disease. Notably, for managing mild cases of seasonal or perennial AR, a significant majority of physicians (60.9%, n=980) preferred fexofenadine as the oral antihistamine of choice. A preference was fexofenadine over levocetrizine, bilastine, desloratadine and cetirizine was noted across chest physicians, ENT specialists, and consulting physicians of the country. This observation underscores the efficacy and favorable tolerability of fexofenadine in patients, as attested by a substantial majority of physicians practicing across India. The findings provide valuable insights into the clinical landscape of AR management and highlight the prominence of fexofenadine as a preferred treatment option among Indian healthcare professionals (19).

• The Ministry of Health & Family Welfare, Government of India, has promulgated standard treatment guidelines for the clinical management of AR within the Indian context. The guidelines advocate the utilization of agents including, Fexofenadine for outpatient management of AR. (12)
• Concurrently, the Association of Otolaryngologists of India has issued its guidelines, designating second-generation antihistamines including fexofenadine, as the primary therapeutic intervention for mild to moderate intermittent and mild persistent AR (1).

Take-Home points:

• Allergic rhinitis (AR) is a prevalent inflammatory nasal condition globally, with varying prevalence rates, notably higher in Southeast Asia, such as India.
• Multiple factors, including genetic influences and environmental exposures, contribute to AR prevalence in India. India grapples with diverse air pollutants, indoor issues, and data gaps, impeding accurate allergy diagnosis characterization.
• Fexofenadine, a prominent second-generation antihistamine is a recommended consideration by the Government of India and emerges as a pivotal element in the comprehensive management of AR. A recently published study in 2024, has reinforced the preference for fexofenadine among the Indian medical fraternity across specialties.
• Recognized for its superior safety profile, cognitive preservation, and potent anti-inflammatory mechanisms, Fexofenadine stands out among anti-histamine treatment options.
• The efficacy demonstrated in diverse clinical studies underlines Fexofenadine's role as a reliable and effective pharmacological consideration in the management of allergic rhinitis.

Adapted from:

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