Safety and Efficacy of Combination Therapy for Allergic Rhinitis Compared to Monotherapies and Placebo

Symptoms of Allergic Rhinitis and Its Therapy

Allergic rhinitis (AR) is a chronic condition caused by the nasal mucosa's reaction to an allergen. Typical symptoms of AR include nasal congestion, sneezing, rhinorrhea, and nasal itching. Additionally, many patients suffer from comorbidities (asthma, obstructive sleep apnea, or sinusitis), which can exacerbate if AR symptoms are not adequately controlled.

The pathogenesis of AR is a complex process involving the activation of several different pro-inflammatory cell types. Therefore, combination therapy with antihistamines and corticosteroids is more effective in alleviating AR symptoms compared to monotherapy.   

GSP301 is a nasal spray containing a fixed combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate, intended to treat symptoms of seasonal AR. The active ingredients are individually effective in treating AR symptoms, and their administration is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the form of an intranasal spray (olopatadine administered 2× and mometasone 1× daily). To determine the optimal dosing of combination therapy, it was necessary to assess the efficacy of 1× and 2× daily dosing compared to placebo and both monotherapies. 

Study Methodology and Course, Evaluated Patient Population

Patients aged 12 and older with a diagnosis of seasonal AR during the mountain cedar pollen season were included in the study. After an initial phase (placebo run-in, 7−10 days from study entry to randomization), the treatment phase followed (15−17 days from randomization to the final visit). Upon randomization, patients were assigned one of seven possible therapies for 14 days (2 sprays into each nostril): GSP301 2× daily (olopatadine 665 μg, mometasone 25 μg), GSP301 1× daily (olopatadine 665 μg, mometasone 50 μg), monotherapy with olopatadine 1× or 2× daily (665 μg), monotherapy with mometasone (1× daily 50 μg or 2× daily 25 μg), placebo.  

To be included in the study, a positive skin prick test (redness ≥ 5 mm beyond the negative control), an average 12-hour nasal symptom score (rTNSS – reflective Total Nasal Symptom Score) ≥ 8 (max. 12), and morning nasal congestion ≥ 2 were required. 

1111 patients were enrolled in the study, and 1085 completed it. The evaluated population mostly consisted of whites and females with an average age of 41.5–45.4 years. At the study's start, patients described nasal and ocular symptoms as moderately severe to severe. Demographic characteristics and symptoms were comparable across groups. 

Findings

In the groups administered GSP301 1× or 2× daily, there was a significant and clinically meaningful improvement in average morning and evening rTNSS from the start to the end of the 14-day treatment phase compared to placebo (p < 0.0001 for both). GSP301 2× daily showed significant and clinically meaningful improvement in rTNSS compared to olopatadine 2× daily (p = 0.049) and mometasone 2× daily (p = 0.004). GSP301 1× daily significantly and clinically improved rTNSS compared to olopatadine 1× daily (p = 0.002), but no clinically meaningful improvement was observed compared to mometasone 1× daily (p = 0.152). 

GSP301 1× or 2× daily significantly improved rTNSS compared to placebo from the first day of application, and improvement in symptoms was observed throughout the 14-day treatment period (p < 0.01). Significant and clinically meaningful improvement was also observed in average morning and evening iTNSS (instantaneous TNSS) for both types of GSP301 application compared to placebo (p < 0.001). 

Adverse events during treatment reported by at least 2% of patients in any group included headache and dysgeusia. In the GSP301 1× daily group, headache was reported by 3.8% of patients. Dysgeusia was only noted in groups with olopatadine. Most reported adverse events were mild to moderate in intensity. 

Conclusion

GSP301 2× daily proved effective and well-tolerated. Compared to placebo and monotherapies, it demonstrated significant and clinically meaningful improvement in rTNSS. 

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Source: Andrews C. P., Mohar D., Salhi Y., Tantry S. K. Efficacy and safety of twice-daily and once-daily olopatadine-mometasone combination nasal spray for seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2020; 124 (2): 171–178.e2, doi: 10.1016/j.anai.2019.11.007.