Allergic Rhinitis-Phenotypes, Challenges, Therapeutic Approach and Role of Montelukast Fexofenadine Combination

Disease Burden and Phenotypes: Allergic rhinitis has distinct traits and may be the most troublesome of all the many allergic illnesses. The disease has a complex etiology, like many other chronic diseases. Several hereditary and environmental factors influence the pathophysiologic processes of AR. Each stage in the pathophysiologic process of AR has unique molecular characteristics. (2)

AR is the most common phenotype of rhinitis. On the basis of aetiology, other phenotypes of rhinitis are classified into allergic (IgE mediated), non-alergic non-infective rhinitis (drug-induced, vasomotor rhinitis, hypothyroidism, etc), infectious (viral, bacteria, etc) and idiopathic. (3)

In children, conjunctivitis and asthma are the common AR phenotype, while watery rhinorrhea is the most prevalent clinical symptom in the elderly. Multiple diseases such as asthma, eczema, atopic dermatitis, conjunctivitis, chronic obstructive pulmonary disease (COPD), food allergy, and sleep apnea are frequently associated with allergic rhinitis. (4)

Indian Risk Factors for AR: Maternal smoking, obesity, indoor pollution heating, indoor pollution cooking, and outdoor pollution are some risk factors for AR in the Indian population. (5)

Challenges of AR In Indian Scenario: While genetic predisposition or environmental exposures are the main risk factors for AR, several new environmental, social, and behavioral risk factors have also been linked to the disease, including the presence of dumpsters and the movement of vehicles close to homes, and exposure to artificial light at night. Due to various factors, including the absence of diagnostic resources, appropriate identification, and therapy of AR are frequently inadequate in India. According to studies, a strategic approach must be created to improve the quality of care for allergic diseases by raising clinicians' and patients' awareness and involving stakeholders and policymakers in making treatments accessible to patients. (1)

Therapy of Allergic Rhinitis:

The current treatment for allergic rhinitis involves avoiding allergens, medication, immunotherapy, and other treatments. The commonly used pharmacological agents are intranasal corticosteroids (INS), antihistamines, and leukotriene receptor antagonists (LTRA). Treatments using multiple drugs, such as INS plus antihistamines or antihistamines plus leukotriene receptor antagonists (LTRAs), are frequently used. Combination agents are often reported as more effective than each taken alone due to the two medications' various complementary mechanisms of action and potential therapeutic goals. (6)

Combining Oral Antihistamines and Leukotriene Receptor Antagonists: Studies evaluating the effectiveness of adjuvant therapy of the two classes of medications for the treatment of allergic rhinitis have suggested that a combination of LTRAs and oral antihistamine H1 can boost the therapeutic efficacy against daytime and composite nasal symptoms, including rhinorrhea, sneezing, and itching. Oral antihistamines inhibit the H1 receptor and alleviate itching, sneezing, and rhinorrhea. In addition to lowering nasal resistance, LRTAs help alleviate other nasal AR symptoms. They do this by inhibiting cysteinyl-leukotrienes. (6)

The Indian Guideline on Allergic Rhinitis formulated by the Association of Otolaryngologists of India also noted that combination therapy might be a reasonable choice, especially in patients whose symptoms are not well controlled with one agent alone, those with pronounces ocular symptoms, or those commencing treatment because of likely faster onset of treatment effects. (3)

Montelukast and Fexofenadine Combination in Allergic Rhinitis- Evidence from Indian Clinical Studies

An Indian study (n=804) evaluated the efficacy and safety of montelukast and fexofenadine fixed-dose combination among patients with allergic rhinitis. All patients were treated with montelukast 10 mg plus fexofenadine 120 mg fixed-dose combination once daily for 14 days.

• The fixed-dose combination of Fexofenadine plus montelukast was significantly effective in reducing total symptom score, total nasal symptom score (nasal congestion, rhinorrhea, nasal itching, and sneezing), and total ocular symptom score [(itching/burning eyes, tearing/ watering eyes, and eye redness) (p<0.0001 for all parameters)].
• The global evaluation of efficacy by patients and investigators reported "excellent to good" efficacy in >95% of patients.

The fixed-dose combination of Fexofenadine plus montelukast was efficacious and well tolerated in allergic rhinitis among Indian adult patients. (7)

Another Indian prospective comparative parallel group study (n=60) found that the fixed-dose combination of Montelukast (10mg) and Fexofenadine (5mg) significantly reduced the total nasal symptoms score, which is a 12-point scale score for 4 symptoms including rhinorrhea, nasal obstruction, sneezing and nasal itching (p<0.001). After 15 days of treatment, 60% of the patients got symptomatically better, and severity decreased in 40% of the patient. This study concluded that the fixed-dose combination of Montelukast and Fexofenadine could effectively treat allergic rhinitis. (8)

Clinical Care Points:

 ✔ Allergic rhinitis (AR) is a chronic disease affecting the quality of life of patients. AR has distinct features in the broad spectrum of allergic diseases and may be the most bothersome.

✔ The diagnosis and management of AR in India are often suboptimal, which further adds to the disease burden.

✔ Two important areas in the treatment of allergic rhinitis are pharmacotherapy and immunotherapy.

✔ The most commonly used treatments are oral or nasal antihistaminics, nasal steroids, leukotriene receptor antagonists, and their combination with antihistamine agents.

✔ Combination agents including LTRAs and oral antihistamines can boost the therapeutic efficacy of allergic rhinitis treatment.

✔ Indian studies have substantiated that combining montelukast with antihistamine agents such as Fexofenadine could increase the treatment efficacy of allergic rhinitis.

Reference

Adapted from

1. Moitra S, Mahesh PA, Moitra S. Allergic rhinitis in India. Clin Exp Allergy. 2023;00:1-12. doi:10.1111/cea.14295

2. Cingi C, Catli T. Phenotyping of allergic rhinitis. Curr Allergy Asthma Rep. 2012;12(2):115-119. doi:10.1007/s11882-012-0243-x

3. Indian Guidelines on Allergic Rhinitis. Formulated by the Association of Otolaryngologists of India. 2021. Retrieved on 13rd June 2023 from http://www.aoiho.org/pdf/AOI%20AR%20Guidelines.pdf

4. Mullol J, Del Cuvillo A, Lockey RF. Rhinitis Phenotypes. J Allergy Clin Immunol Pract. 2020;8(5):1492-1503. doi:10.1016/j.jaip.2020.02.00

5. Mahesh PA, Moitra S, Mabalirajan U, et al. Allergic diseases in India – Prevalence, risk factors and current challenges. Clin Exp Allergy. 2023;53:276-294.doi: 10.1111/cea.14239

6. Liu G, Zhou X, Chen J, Liu F. Oral Antihistamines Alone vs in Combination with Leukotriene Receptor Antagonists for Allergic Rhinitis: A Meta-analysis. Otolaryngol Head Neck Surg. 2018;158(3):450-458. doi:10.1177/0194599817752624

7. Naik M, Khandeparkar P, Nayak A, Mukaddam Q. Efficacy and safety of montelukast plus fexofenadine fixed-dose combination in allergic rhinitis: Results of a post-marketing study in India. Indian Medical Gazette 2013:314-8.

8. Soumya Annu Achankunju, S. Rajaram, K. Mukesh, Anakha Kaladharan. A comparative study of efficacy and safety of montelukast levocetirizine and montelukast fexofenadine in patients with allergic rhinitis. 2021. World Journal of Pharmaceutical Research. DOI: 10.20959/wjpr20221-22744